Pro-protein convertases control the maturation and processing of the iron-regulatory protein, RGMc/hemojuvelin

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Rotwein Peter

2008-04-01

Full Text Available Abstract Background Repulsive guidance molecule c (RGMc or hemojuvelin, a glycosylphosphatidylinositol-linked glycoprotein expressed in liver and striated muscle, plays a central role in systemic iron balance. Inactivating mutations in the RGMc gene cause juvenile hemochromatosis (JH, a rapidly progressing iron storage disorder with severe systemic manifestations. RGMc undergoes complex biosynthetic steps leading to membrane-bound and soluble forms of the protein, including both 50 and 40 kDa single-chain species. Results We now show that pro-protein convertases (PC are responsible for conversion of 50 kDa RGMc to a 40 kDa protein with a truncated COOH-terminus. Unlike related molecules RGMa and RGMb, RGMc encodes a conserved PC recognition and cleavage site, and JH-associated RGMc frame-shift mutants undergo COOH-terminal cleavage only if this site is present. A cell-impermeable peptide PC inhibitor blocks the appearance of 40 kDa RGMc in extra-cellular fluid, as does an engineered mutation in the conserved PC recognition sequence, while the PC furin cleaves 50 kDa RGMc in vitro into a 40 kDa molecule with an intact NH2-terminus. Iron loading reduces release of RGMc from the cell membrane, and diminishes accumulation of the 40 kDa species in cell culture medium. Conclusion Our results define a role for PCs in the maturation of RGMc that may have implications for the physiological actions of this critical iron-regulatory protein.

An atypical proprotein convertase in Giardia lamblia differentiation.

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Davids, B J; Gilbert, M A; Liu, Q; Reiner, D S; Smith, A J; Lauwaet, T; Lee, C; McArthur, A G; Gillin, F D

2011-02-01

Proteolytic activity is important in the lifecycles of parasites and their interactions with hosts. Cysteine proteases have been best studied in Giardia, but other protease classes have been implicated in growth and/or differentiation. In this study, we employed bioinformatics to reveal the complete set of putative proteases in the Giardia genome. We identified 73 peptidase homologs distributed over 5 catalytic classes in the genome. Serial analysis of gene expression of the G. lamblia lifecycle found thirteen protease genes with significant transcriptional variation over the lifecycle, with only one serine protease transcript upregulated late in encystation. The translated gene sequence of this encystation-specific transcript was most similar to eukaryotic subtilisin-like proprotein convertases (SPC), although the typical catalytic triad was not identified. Epitope-tagged gSPC protein expressed in Giardia under its own promoter was upregulated during encystation with highest expression in cysts and it localized to encystation-specific secretory vesicles (ESV). Total gSPC from encysting cells produced proteolysis in gelatin gels that co-migrated with the epitope-tagged protease in immunoblots. Immuno-purified gSPC also had gelatinase activity. To test whether endogenous gSPC activity is involved in differentiation, trophozoites and cysts were exposed to the specific serine proteinase inhibitor 4-(2-aminoethyl)-benzenesulfonyl fluoride hydrochloride (AEBSF). After 21 h encystation, a significant decrease in ESV was observed with 1mM AEBSF and by 42 h the number of cysts was significantly reduced, but trophozoite growth was not inhibited. Concurrently, levels of cyst wall proteins 1 and 2, and AU1-tagged gSPC protein itself were decreased. Excystation of G. muris cysts was also significantly reduced in the presence of AEBSF. These results support the idea that serine protease activity is essential for Giardia encystation and excystation. Copyright © 2010 Elsevier B

Chemical Constituents with Proprotein Convertase Subtilisin/Kexin Type 9 mRNA Expression Inhibitory Activity from Dried Immature Morus alba Fruits.

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Pel, Pisey; Chae, Hee-Sung; Nhoek, Piseth; Kim, Young-Mi; Chin, Young-Won

2017-07-05

Phytochemical investigation for a chloroform-soluble extract of dried Morus alba fruits, selected by proprotein convertase subtilisin-kexin type 9 (PCSK9) mRNA expression monitoring assay in HepG2 cells, led to the isolation of a new benzofuran, isomoracin D (1), and a naturally occurring compound, N-(N-benzoyl-l-phenylalanyl)-l-phenylalanol (2), along with 13 known compounds (3-15). All of the structures were established by NMR spectroscopic data as well as MS analysis. Of the isolates, moracin C (7) was found to inhibit PCSK9 mRNA expression with an IC 50 value of 16.8 μM in the HepG2 cells.

Complexity of mechanisms among human proprotein convertase subtilisin-kexin type 9 variants.

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Dron, Jacqueline S; Hegele, Robert A

2017-04-01

There are many reports of human variants in proprotein convertase subtilisin-kexin type 9 (PCSK9) that are either gain-of-function (GOF) or loss-of-function (LOF), with downstream effects on LDL cholesterol and cardiovascular disease (CVD) risk. However, data on particular mechanisms have only been minimally curated. GOF variants are individually ultrarare, affect all domains of the protein, act to reduce LDL receptor expression through several mechanisms, are a minor cause of familial hypercholesterolemia, have been reported mainly within families, have variable LDL cholesterol-raising effects, and are associated with increased CVD risk mainly through observational studies in families and small cohorts. In contrast, LOF variants can be either ultrarare mutations or relatively more common polymorphisms seen in populations, affect all domains of the protein, act to increase LDL receptor expression through several mechanisms, have variable LDL cholesterol-lowering effects, and have been associated with decreased CVD risk mainly through Mendelian randomization studies in epidemiologic populations. There is considerable complexity underlying the clinical concept of both LOF and GOF variants of PCSK9. But despite the underlying mechanistic heterogeneity, altered PCSK9 secretion or function is ultimately correlated with plasma LDL cholesterol level, which is also the driver of CVD outcomes.

Propeptides are sufficient to regulate organelle-specific pH-dependent activation of furin and proprotein convertase 1/3.

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Dillon, Stephanie L; Williamson, Danielle M; Elferich, Johannes; Radler, David; Joshi, Rajendra; Thomas, Gary; Shinde, Ujwal

2012-10-12

The proprotein convertases (PCs) furin and proprotein convertase 1/3 (PC1) cleave substrates at dibasic residues along the eukaryotic secretory/endocytic pathway. PCs are evolutionarily related to bacterial subtilisin and are synthesized as zymogens. They contain N-terminal propeptides (PRO) that function as dedicated catalysts that facilitate folding and regulate activation of cognate proteases through multiple-ordered cleavages. Previous studies identified a histidine residue (His69) that functions as a pH sensor in the propeptide of furin (PRO(FUR)), which regulates furin activation at pH~6.5 within the trans-Golgi network. Although this residue is conserved in the PC1 propeptide (PRO(PC1)), PC1 nonetheless activates at pH~5.5 within the dense core secretory granules. Here, we analyze the mechanism by which PRO(FUR) regulates furin activation and examine why PRO(FUR) and PRO(PC1) differ in their pH-dependent activation. Sequence analyses establish that while both PRO(FUR) and PRO(PC1) are enriched in histidines when compared with cognate catalytic domains and prokaryotic orthologs, histidine content in PRO(FUR) is ~2-fold greater than that in PRO(PC1), which may augment its pH sensitivity. Spectroscopy and molecular dynamics establish that histidine protonation significantly unfolds PRO(FUR) when compared to PRO(PC1) to enhance autoproteolysis. We further demonstrate that PRO(FUR) and PRO(PC1) are sufficient to confer organelle sensing on folding and activation of their cognate proteases. Swapping propeptides between furin and PC1 transfers pH-dependent protease activation in a propeptide-dictated manner in vitro and in cells. Since prokaryotes lack organelles and eukaryotic PCs evolved from propeptide-dependent, not propeptide-independent prokaryotic subtilases, our results suggest that histidine enrichment may have enabled propeptides to evolve to exploit pH gradients to activate within specific organelles. Copyright © 2012 Elsevier Ltd. All rights reserved.

Impact of diet and exercise on proprotein convertase subtilisin/kexin 9: A mini-review.

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Saely, Christoph H; Drexel, Heinz

2016-12-01

Proprotein Convertase Subtilisin/Kexin 9 (PCSK9) plays an important role in the regulation of blood cholesterol levels, and inhibition of PCSK9 with monoclonal antibodies reduces LDL cholesterol by more than 50% over and above what can be achieved with statins or ezetimibe alone. Diet and exercise influence PCSK9 levels; however data on this issue are scarce. Regarding diet, a high oleic canola/docosahexaenoic acid oil blend, marine n-3 polyunsaturated fatty acids, vegetable n-6 polyunsaturated fatty acids, a Mediterranean style diet and acute fasting, but not necessarily weight reduction are associated with low PCSK9 concentrations, whereas a high fructose diet is associated with high PCSK9 concentrations. Animal data regarding the effect of diet on PCSK9 must be interpreted with caution, because even between rodent species, significant differences become apparent. Regarding exercise, a decrease in PCSK9 has been reported in one investigation along with an intervention promoting active use of stairs rather than elevators. Reports from sparse animal studies regarding the effect of exercise on PCSK9 have yielded varying results. Copyright © 2016. Published by Elsevier Inc.

Long-Term Follow-up of a Case with Proprotein Convertase 1/3 Deficiency: Transient Diabetes Mellitus with Intervening Diabetic Ketoacidosis During Growth Hormone Therapy.

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Gönç, E. Nazlı; Özön, Alev; Alikaşifoğlu, Ayfer; Kandemir, Nurgün

2017-09-01

Proprotein convertase 1/3 (PC1/3) deficiency is a very rare disease characterized by severe intractable diarrhea in the first years of life, followed by obesity and several hormonal deficiencies later. Diabetes mellitus requiring insulin treatment and diabetic ketoacidosis have not been reported in this disorder. We herein present a girl with PC1/3 deficiency who has been followed from birth to 17 years of age. She developed deficiencies of all pituitary hormones over time as well as diabetes mellitus while receiving growth hormone (GH) therapy. She was complicated with diabetic ketoacidosis during dietary management of diabetes mellitus, thus insulin treatment was initiated. Insulin requirement to regulate hyperglycemia was short-lived. Repeat oral glucose tolerance test five years later was normal. The findings of this patient show that diabetes mellitus can develop at any time during follow-up of cases with proportein convertase 1/3 deficiency especially under GH therapy.

Transgenic Overexpression of the Proprotein Convertase Furin Enhances Skin Tumor Growth

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Jian Fu

2012-04-01

Full Text Available Furin, one of the members of the family of proprotein convertases (PCs, ubiquitously expressed as a type I membrane-bound proteinase, activates several proteins that contribute to tumor progression. In vitro studies using cancer cell lines and clinical specimens demonstrated that furin processes important substrates such as insulin-like growth factor 1 receptor (IGF-1R and transforming growth factor β, leading to increased tumor growth and progression. Despite the numerous studies associating furin with tumor development, its effects in preclinical models has not been comprehensively studied. In this study, we sought to determine the protumorigenic role of furin in vivo after a two-stage chemical carcinogenesis protocol in transgenic mice in which furin expression was targeted to the epidermal basal layer. We found that processing of the PC substrate IGF-1R and the proliferation rate of mouse epidermis was enhanced in transgenic mice when compared with their WT counterparts. Histopathologic diagnoses of the tumors demonstrated that furin transgenic mice (line F47 developed twice as many squamous carcinomas as the control, WT mice (P < .002. Similarly, tumors cells from transgenic mice were able to process PC substrates more efficiently than tumor cells from WT mice. Furthermore, furin expression resulted in a higher SCC volume in transgenic mice as well as an increase in the percentage of high-grade SCC, including poorly differentiated and spindle cell carcinomas. In conclusion, expression of furin in the basal layer of the epidermis increased tumor development and enhanced tumor growth, supporting the consideration of furin as a potential target for cancer treatment.

The Proprotein Convertase KPC-1/Furin Controls Branching and Self-avoidance of Sensory Dendrites in Caenorhabditis elegans

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Bülow, Hannes E.

2014-01-01

Animals sample their environment through sensory neurons with often elaborately branched endings named dendritic arbors. In a genetic screen for genes involved in the development of the highly arborized somatosensory PVD neuron in C. elegans, we have identified mutations in kpc-1, which encodes the homolog of the proprotein convertase furin. We show that kpc-1/furin is necessary to promote the formation of higher order dendritic branches in PVD and to ensure self-avoidance of sister branches, but is likely not required during maintenance of dendritic arbors. A reporter for kpc-1/furin is expressed in neurons (including PVD) and kpc-1/furin can function cell-autonomously in PVD neurons to control patterning of dendritic arbors. Moreover, we show that kpc-1/furin also regulates the development of other neurons in all major neuronal classes in C. elegans, including aspects of branching and extension of neurites as well as cell positioning. Our data suggest that these developmental functions require proteolytic activity of KPC-1/furin. Recently, the skin-derived MNR-1/menorin and the neural cell adhesion molecule SAX-7/L1CAM have been shown to act as a tripartite complex with the leucine rich transmembrane receptor DMA-1 on PVD mechanosensory to orchestrate the patterning of dendritic branches. Genetic analyses show that kpc-1/furin functions in a pathway with MNR-1/menorin, SAX-7/L1CAM and DMA-1 to control dendritic branch formation and extension of PVD neurons. We propose that KPC-1/furin acts in concert with the ‘menorin’ pathway to control branching and growth of somatosensory dendrites in PVD. PMID:25232734

Proprotein Convertase Subtilisin Kexin Type 9 Inhibition for Autosomal Recessive Hypercholesterolemia-Brief Report.

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Thedrez, Aurélie; Sjouke, Barbara; Passard, Maxime; Prampart-Fauvet, Simon; Guédon, Alexis; Croyal, Mikael; Dallinga-Thie, Geesje; Peter, Jorge; Blom, Dirk; Ciccarese, Milco; Cefalù, Angelo B; Pisciotta, Livia; Santos, Raul D; Averna, Maurizio; Raal, Frederick; Pintus, Paolo; Cossu, Maria; Hovingh, Kees; Lambert, Gilles

2016-08-01

Proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors lower low-density lipoprotein (LDL) cholesterol in the vast majority of patients with autosomal dominant familial hypercholesterolemia. Will PCSK9 inhibition with monoclonal antibodies, in particular alirocumab, be of therapeutic value for patients with autosomal recessive hypercholesterolemia (ARH)? Primary lymphocytes were obtained from 28 genetically characterized ARH patients and 11 controls. ARH lymphocytes treated with mevastatin were incubated with increasing doses of recombinant PCSK9 with or without saturating concentrations of alirocumab. Cell surface LDL receptor expression measured by flow cytometry and confocal microscopy was higher in ARH than in control lymphocytes. PCSK9 significantly reduced LDL receptor expression in ARH lymphocytes albeit to a lower extent than in control lymphocytes (25% versus 76%, respectively), an effect reversed by alirocumab. Fluorescent LDL cellular uptake, also measured by flow cytometry, was reduced in ARH lymphocytes compared with control lymphocytes. PCSK9 significantly lowered LDL cellular uptake in ARH lymphocytes, on average by 18%, compared with a 46% reduction observed in control lymphocytes, an effect also reversed by alirocumab. Overall, the effects of recombinant PCSK9, and hence of alirocumab, on LDL receptor expression and function were significantly less pronounced in ARH than in control cells. PCSK9 inhibition with alirocumab on top of statin treatment has the potential to lower LDL cholesterol in some autosomal recessive hypercholesterolemia patients. © 2016 American Heart Association, Inc.

[Blood Levels of Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) in Men from Different Population Groups and Its Relation to Unfavorable Long-Term Prognosis].

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Ragino, Yu I; Astrakova, K S; Shakhtshneider, E V; Stakhneva, E M; Gafarov, V V; Bogatyrev, S N; Voevoda, M I

2017-04-01

of the study was to investigate blood levels of proprotein convertase subtilisin/kexin type 9 (PCSK9) in men from different population subgroups, their associations with cardiovascular risk factors and with unfavorable 7-years long-term prognosis. The study included three subgroups of men from a population sample of residents of Novosibirsk, 44-73 years old, not receiving lipid-lowering drugs: subgroup of population proper (183 men), subgroup with hypercholesterolemia (46 men), and subgroup with hypocholesterolemia (18 men). Blood level of PCSK9 was determined by ELISA using the test-systems "Human Proprotein Convertase 9/PCSK9 Immunoassay". Study endpoints (myocardial infarction, cardiovascular death) were registered during 7 years after baseline examination of subgroups using the data of the Registers of myocardial infarction and cardiovascular mortality. Distribution of PCSK9 protein in subgroups with hyper- and hypocholesterolemia was normal. In the subgroup of population proper it was abnormal with leftward shift. PCSK9 protein concentration in the subgroup with hypercholesterolemia was 1.2 times higher than in the population subgroup. PCSK9 protein level correlated significantly with blood levels of total cholesterol (CH), low density lipoprotein (LDL) CH, and glucose. Only 15% of PCSK9 variability was due to the influence of other factors (R Square=0.155, pblood level of PCSK9 protein were levels of high density lipoprotein CH (=0.238, p=0.023), triglycerides (=0.253, p=0.049) and LDL CH (=0.751, p=0.009). Multivariate regression analysis revealed significant independent association of PCSK9 protein levels with cardiovascular death during period of registration (7-years) (p=0.048, OR=1.01). This result indicates that in men increase of blood level of PCSK9 protein by 1ng/ml independently of other parameters increases relative risk of cardiovascular death during following 7 years by 1%.

Common Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Epitopes Mediate Multiple Routes for Internalization and Function

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DeVay, Rachel M.; Yamamoto, Lynn; Shelton, David L.; Liang, Hong

2015-01-01

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a soluble protein that directs membrane-bound receptors to lysosomes for degradation. In the most studied example of this, PCSK9 binding leads to the degradation of low density lipoprotein receptor (LDLR), significantly affecting circulating LDL-C levels. The mechanism mediating this degradation, however, is not completely understood. We show here that LDLR facilitates PCSK9 interactions with amyloid precursor like protein 2 (APLP2) at neutral pH leading to PCSK9 internalization, although direct binding between PCSK9 and LDLR is not required. Moreover, binding to APLP2 or LDLR is independently sufficient for PCSK9 endocytosis in hepatocytes, while LDL can compete with APLP2 for PCSK9 binding to indirectly mediate PCSK9 endocytosis. Finally, we show that APLP2 and LDLR are also required for the degradation of another PCSK9 target, APOER2, necessitating a general role for LDLR and APLP2 in PCSK9 function. Together, these findings provide evidence that PCSK9 has at least two endocytic epitopes that are utilized by a variety of internalization mechanisms and clarifies how PCSK9 may direct proteins to lysosomes. PMID:25905719

Potential role of lycopene in targeting proprotein convertase subtilisin/kexin type-9 to combat hypercholesterolemia.

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Sultan Alvi, Sahir; Ansari, Irfan A; Khan, Imran; Iqbal, Johar; Khan, M Salman

2017-07-01

Proprotein convertase subtilisin/kexin type 9 (PCSK-9) is a serine protease of the proprotien convertase (PC) family that has profound effects on plasma low density lipoprotein cholesterol (LDL-C) levels, the major risk factor for coronary heart disease (CHD), through its ability to mediate LDL receptor (LDL-R) protein degradation and reduced recycling to the surface of hepatocytes. Thus, the current study was premeditated not only to evaluate the role of lycopene in targeting the inhibition of PCSK-9 via modulation of genes involved in cholesterol homeostasis in HFD rats but also to examine a correlation between HFD induced inflammatory cascades and subsequent regulation of PCSK-9 expression. Besides the effect of lycopene on hepatic PCSK-9 gene expression, PPI studies for PCSK-9-Lycopene complex and EGF-A of LDL-R were also performed via molecular informatics approach to assess the dual mode of action of lycopene in LDL-R recycling and increased removal of circulatory LDL-C. We for the first time deciphered that lycopene treatment significantly down-regulates the expression of hepatic PCSK-9 and HMGR, whereas, hepatic LDL-R expression was significantly up-regulated. Furthermore, lycopene ameliorated inflammation stimulated expression of PCSK-9 via suppressing the expression of inflammatory markers. The results from our molecular informatics studies confirmed that lycopene, while occupying the active site of PCSK-9 crystal structure, reduces the affinity of PCSK-9 to complex with EGF-A of LDL-R, whereas, atorvastatin makes PCSK-9-EGF-A complex formation more feasible than both of PCSK-9-EGF-A alone and Lycopene-PCSK-9-EGF-A complex. Based on above results, it can be concluded that lycopene exhibits potent hypolipidemic activities via molecular mechanisms that are either identical (HMGR inhibition) or distinct from that of statins (down-regulation of PCSK-9 mRNA synthesis). To the best of our knowledge, this is the first report that lycopene has this specific

Proprotein convertase subtilisin/kexin type 7 (PCSK7) is essential for the zebrafish development and bioavailability of transforming growth factor β1a (TGFβ1a).

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Turpeinen, Hannu; Oksanen, Anna; Kivinen, Virpi; Kukkurainen, Sampo; Uusimäki, Annemari; Rämet, Mika; Parikka, Mataleena; Hytönen, Vesa P; Nykter, Matti; Pesu, Marko

2013-12-20

Proprotein convertase subtilisin/kexin (PCSK) enzymes convert proproteins into bioactive end products. Although other PCSK enzymes are known to be essential for biological processes ranging from cholesterol metabolism to host defense, the in vivo importance of the evolutionarily ancient PCSK7 has remained enigmatic. Here, we quantified the expressions of all pcsk genes during the 1st week of fish development and in several tissues. pcsk7 expression was ubiquitous and evident already during the early development. To compare mammalian and zebrafish PCSK7, we prepared homology models, which demonstrated remarkable structural conservation. When the PCSK7 function in developing larvae was inhibited, we found that PCSK7-deficient fish have defects in various organs, including the brain, eye, and otic vesicle, and these result in mortality within 7 days postfertilization. A genome-wide analysis of PCSK7-dependent gene expression showed that, in addition to developmental processes, several immune system-related pathways are also regulated by PCSK7. Specifically, the PCSK7 contributed to the mRNA expression and proteolytic cleavage of the cytokine TGFβ1a. Consequently, tgfβ1a morphant fish displayed phenotypical similarities with pcsk7 morphants, underscoring the importance of this cytokine in the zebrafish development. Targeting PCSK activity has emerged as a strategy for treating human diseases. Our results suggest that inhibiting PCSK7 might interfere with normal vertebrate development.

Activation of Adiponectin Receptor Regulates Proprotein Convertase Subtilisin/Kexin Type 9 Expression and Inhibits Lesions in ApoE-Deficient Mice.

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Sun, Lei; Yang, Xiaoxiao; Li, Qi; Zeng, Peng; Liu, Ying; Liu, Lipei; Chen, Yuanli; Yu, Miao; Ma, Chuanrui; Li, Xiaoju; Li, Yan; Zhang, Rongxin; Zhu, Yan; Miao, Qing Robert; Han, Jihong; Duan, Yajun

2017-07-01

The reduced adiponectin levels are associated with atherosclerosis. Adiponectin exerts its functions by activating adiponectin receptor (AdipoR). Proprotein convertase subtilisin kexin type 9 (PCSK9) degrades LDLR protein (low-density lipoprotein receptor) to increase serum LDL-cholesterol levels. PCSK9 expression can be regulated by PPARγ (peroxisome proliferator-activated receptor γ) or SREBP2 (sterol regulatory element-binding protein 2). The effects of AdipoR agonists on PCSK9 and LDLR expression, serum lipid profiles, and atherosclerosis remain unknown. At cellular levels, AdipoR agonists (ADP355 and AdipoRon) induced PCSK9 transcription/expression that solely depended on activation of PPAR-responsive element in the PCSK9 promoter. AdipoR agonists induced PPARγ expression; thus, the AdipoR agonist-activated PCSK9 expression/production was impaired in PPARγ deficient hepatocytes. Meanwhile, AdipoR agonists transcriptionally activated LDLR expression by activating SRE in the LDLR promoter. Moreover, AMP-activated protein kinase α (AMPKα) was involved in AdipoR agonist-activated PCSK9 expression. In wild-type mice, ADP355 increased PCSK9 and LDLR expression and serum PCSK9 levels, which was associated with activation of PPARγ, AMPKα and SREBP2 and reduction of LDL-cholesterol levels. In contrast, ADP355 reduced PCSK9 expression/secretion in apoE-deficient (apoE -/- ) mice, but it still activated hepatic LDLR, PPARγ, AMPKα, and SREBP2. More importantly, ADP355 inhibited lesions in en face aortas and sinus lesions in aortic root in apoE -/- mice with amelioration of lipid profiles. Our study demonstrates that AdipoR activation by agonists regulated PCSK9 expression differently in wild-type and apoE -/- mice. However, ADP355 activated hepatic LDLR expression and ameliorated lipid metabolism in both types of mice and inhibited atherosclerosis in apoE -/- mice. © 2017 American Heart Association, Inc.

Induction of atherosclerosis in mice and hamsters without germline genetic engineering

DEFF Research Database (Denmark)

Bjørklund, Martin Mæng; Hollensen, Anne Kruse; Hagensen, Mette Kallestrup

2014-01-01

RATIONALE: Atherosclerosis can be achieved in animals by germline genetic engineering, leading to hypercholesterolemia, but such models are constrained to few species and strains, and they are difficult to combine with other powerful techniques involving genetic manipulation or variation. OBJECTIVE......: To develop a method for induction of atherosclerosis without germline genetic engineering. METHODS AND RESULTS: Recombinant adeno-associated viral vectors were engineered to encode gain-of-function proprotein convertase subtilisin/kexin type 9 mutants, and mice were given a single intravenous vector...... injection followed by high-fat diet feeding. Plasma proprotein convertase subtilisin/kexin type 9 and total cholesterol increased rapidly and were maintained at high levels, and after 12 weeks, mice had atherosclerotic lesions in the aorta. Histology of the aortic root showed progression of lesions...

Inhibitory proproteinowej konwertazy subtylizyny/keksyny 9 nowym, przełomowym narzędziem terapeutycznym w leczeniu dyslipidemii = Proprotein convertase subtilisin/kexin type 9 inhibitors are a new, groundbreaking therapeutic tool in the treatment of dyslipidemia

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Łukasz Wołowiec

2016-07-01

 concentartion of LDL cholesterol. Proprotein convertase subtilisin/kexin type 9 (PCSK9 inhibitors (a  new class of drugs  that regulate the concentration of LDL cholesterol receptor seem to be a  new and effective therapeutic tool used to reach the target level of LDL cholesterol. The aim of the study was to present the cholesterol metabolism in human body, the significance of an effective therapy for lipid disorders as well as the current knowledge of the PCSK9 protein and its inhibitors.   Key words: cholesterol, proprotein convertase subtilisin/kexin type (PCSK9, PCSK9 inhibitors.

'LDL-C' = LDL-C + Lp(a)-C: implications of achieved ultra-low LDL-C levels in the proprotein convertase subtilisin/kexin type 9 era of potent LDL-C lowering.

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Yeang, Calvin; Witztum, Joseph L; Tsimikas, Sotirios

2015-06-01

The measurement that is termed 'LDL-cholesterol' (LDL-C) includes the cholesterol content of lipoprotein(a) [Lp(a)-C], which can contribute approximately 30-45% to measured LDL-C levels as a percentage of its mass. We review the implications of achieved very low LDL-C levels in patients treated with potent LDL-C-lowering agents in the context of varying Lp(a) levels. Combination therapy with statins, ezetimibe, and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors can lower LDL-C to unprecedentedly low levels. Recent PCSK9 trials have shown that routine achievement of mean LDL-C less than 50 mg/dl is feasible, along with the modest reductions in Lp(a). Many patients will achieve LDL-C less than 25 mg/dl with concomitantly elevated Lp(a) levels that contribute substantially to the measured 'LDL-C'. Therefore, it is possible that some of these patients may have little to no circulating LDL-C. As the new era of ultralow LDL-C levels ensues, it is imperative to understand the contribution of Lp(a)-C to measured LDL-C and the consequences of achieving ultralow or potentially absent LDL-C in the setting of elevated Lp(a) levels and possibly free apo(a). We review this concept and suggest avenues of research, including analyses of existing datasets in current clinical trials and new research studies, to understand its pathophysiological and clinical significance.

Association of a 3' untranslated region polymorphism in proprotein convertase subtilisin/kexin type 9 with HIV viral load and CD4+ levels in HIV/hepatitis C virus coinfected women.

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Kuniholm, Mark H; Liang, Hua; Anastos, Kathryn; Gustafson, Deborah; Kassaye, Seble; Nowicki, Marek; Sha, Beverly E; Pawlowski, Emilia J; Gange, Stephen J; Aouizerat, Bradley E; Pushkarsky, Tatiana; Bukrinsky, Michael I; Prasad, Vinayaka R

2017-11-28

To assess variation in genes that regulate cholesterol metabolism in relation to the natural history of HIV infection. Cross-sectional and longitudinal analysis of the Women's Interagency HIV Study. We examined 2050 single nucleotide polymorphisms (SNPs) in 19 genes known to regulate cholesterol metabolism in relation to HIV viral load and CD4 T-cell levels in a multiracial cohort of 1066 antiretroviral therapy-naive women. Six SNPs were associated with both HIV viral load and CD4 T-cell levels at a false discovery rate of 0.01. Bioinformatics tools did not predict functional activity for five SNPs, located in introns of nuclear receptor corepressor 2, retinoid X receptor alpha (RXRA), and tetratricopeptide repeat domain 39B. Rs17111557 located in the 3' untranslated region of proprotein convertase subtilisin/kexin type 9 (PCSK9) putatively affects binding of hsa-miR-548t-5p and hsa-miR-4796-3p, which could regulate PCSK9 expression levels. Interrogation of rs17111557 revealed stronger associations in the subset of women with HIV/hepatitis C virus (HCV) coinfection (n = 408, 38% of women). Rs17111557 was also associated with low-density lipoprotein cholesterol levels in HIV/HCV coinfected (β: -10.4; 95% confidence interval: -17.9, -2.9; P = 0.007), but not in HIV monoinfected (β:1.2; 95% confidence interval: -6.3, 8.6; P = 0.76) women in adjusted analysis. PCSK9 polymorphism may affect HIV pathogenesis, particularly in HIV/HCV coinfected women. A likely mechanism for this effect is PCSK9-mediated regulation of cholesterol metabolism. Replication in independent cohorts is needed to clarify the generalizability of the observed associations.

A phase 1 study to evaluate the safety and LDL cholesterol-lowering effects of RG7652, a fully human monoclonal antibody against proprotein convertase subtilisin/kexin type 9.

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Baruch, Amos; Luca, Diana; Kahn, Robert S; Cowan, Kyra J; Leabman, Maya; Budha, Nageshwar R; Chiu, Cecilia P C; Wu, Yan; Kirchhofer, Daniel; Peterson, Andrew; Davis, John C; Tingley, Whittemore G

2017-07-01

Proprotein convertase subtilisin/kexin type 9 (PCSK9) downregulates low-density lipoprotein (LDL) receptors, thereby leading to a rise in circulating LDL cholesterol (LDL-C). RG7652 is a fully human monoclonal antibody against PCSK9. This placebo-controlled, phase 1 ascending-dose study in healthy subjects evaluated the safety of RG7652 and its efficacy as a potential LDL-C-lowering drug. Anti-PCSK9 antibody therapy safely and effectively reduces LDL-C. Subjects (N = 80) were randomized into 10 cohorts. Six sequential single-dose cohorts received 10, 40, 150, 300, 600, or 800 mg of RG7652 via subcutaneous injection. Four multiple-dose cohorts received 40 or 150 mg of RG7652 once weekly for 4 weeks, either with or without statin therapy (atorvastatin). Adverse events (AEs) were generally mild; the most common AEs were temporary injection-site reactions. No serious AEs, severe AEs, AEs leading to study-drug discontinuation, or dose-limiting toxicities were reported. RG7652 monotherapy reduced mean LDL-C levels by up to 64% and as much as 100 mg/dL at week 2; the effect magnitude and duration increased with dose (≥57 days following a single RG7652 dose ≥300 mg). Exploratory analyses showed reduced oxidized LDL, lipoprotein(a), and lipoprotein-associated phospholipase A2 with RG7652. Antidrug antibody against RG7652 tested positive in 2 of 60 (3.3%) RG7652-treated and in 4 of 20 (20.0%) placebo-treated subjects. Simultaneous atorvastatin administration did not appear to impact the pharmacokinetic profile or lipid-lowering effects of RG7652. Overall, RG7652 elicited substantial and sustained dose-related LDL-C reductions with an acceptable safety profile and minimal immunogenicity. © 2017 Wiley Periodicals, Inc.

Dietary high oleic canola oil supplemented with docosahexaenoic acid attenuates plasma proprotein convertase subtilisin kexin type 9 (PCSK9) levels in participants with cardiovascular disease risk: A randomized control trial.

Science.gov (United States)

Pu, Shuaihua; Rodríguez-Pérez, Celia; Ramprasath, Vanu Ramkumar; Segura-Carretero, Antonio; Jones, Peter J H

2016-12-01

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a novel circulating protein which plays an important role in regulation of cholesterol metabolism by promoting hepatic LDL receptor degradation. However, the action of dietary fat composition on PCSK9 levels remains to be fully elucidated. The objective was to investigate the action of different dietary oils on circulating PCSK9 levels in the Canola Oil Multicenter Intervention Trial (COMIT). COMIT employed a double-blinded crossover randomized control design, consisting of five 30-d treatment periods. Diets were provided based on a 3000Kcal/d intake, including a 60g/d treatment of conventional canola oil (Canola), a high oleic canola/DHA oil blend (CanolaDHA), a corn/safflower oil blend (CornSaff), a flax/safflower oil blend (FlaxSaff) or a high oleic canola oil (CanolaOleic). Plasma PCSK9 levels were assessed using ELISA at the end of each phase. Lipid profiles (n=84) showed that CanolaDHA feeding resulted in the highest (P<0.05) serum total cholesterol (TC, 5.06±0.09mmol/L) and LDL-cholesterol levels (3.15±0.08mmol/L) across all five treatments. CanolaDHA feeding also produced the lowest (P<0.05) plasma PCSK9 concentrations (216.42±8.77ng/mL) compared to other dietary oil treatments. Plasma PCSK9 levels positively correlated (P<0.05) with serum TC, LDL-cholesterol, apolipoprotein A, and apolipoprotein B levels but did not correlate to HDL-cholesterol levels. Results indicate that post-treatment response in PCSK9 may be altered with the CanolaDHA diet. In conclusion, the elevated LDL-C levels from a DHA oil treatment may not be relevant for the observed decline in PCSK9 levels. Copyright © 2016 Elsevier Inc. All rights reserved.

Treatment-Induced Viral Cure of Hepatitis C Virus-Infected Patients Involves a Dynamic Interplay among three Important Molecular Players in Lipid Homeostasis: Circulating microRNA (miR)-24, miR-223, and Proprotein Convertase Subtilisin/Kexin Type 9.

Science.gov (United States)

Hyrina, Anastasia; Olmstead, Andrea D; Steven, Paul; Krajden, Mel; Tam, Edward; Jean, François

2017-09-01

In patients with chronic hepatitis C virus (HCV) infection, viral hijacking of the host-cell biosynthetic pathways is associated with altered lipid metabolism, which contributes to disease progression and may influence antiviral response. We investigated the molecular interplay among four key regulators of lipid homeostasis [microRNA (miR)-122, miR-24, miR-223, and proprotein convertase subtilisin/kexin type 9 (PCSK9)] in HCV-infected patients (n=72) who achieved a treatment-based viral cure after interferon-based therapy with first-generation direct-acting antivirals. Real-time PCR was used to quantify microRNA plasma levels, and ELISA assays were used to determine plasma concentrations of PCSK9. We report that levels of miR-24 and miR-223 significantly increased in patients achieving sustained virologic response (SVR), whereas the levels of miR-122, a liver-specific cofactor for HCV infection, decreased in these patients. PCSK9 concentrations were significantly increased in SVRs, suggesting that PCSK9 may help impede viral infection. The modulatory effect of PCSK9 on HCV infection was also demonstrated in the context of HCV-infected Huh-7.5.1 cells employing recombinant human PCSK9 mutants. Together, these results provide insights into a novel coordinated interplay among three important molecular players in lipid homeostasis - circulating miR-24, miR-223 and PCSK9 - whose regulation is affected by HCV infection and treatment-based viral cure. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

A novel method for direct measurement of complement convertases activity in human serum.

Science.gov (United States)

Blom, A M; Volokhina, E B; Fransson, V; Strömberg, P; Berghard, L; Viktorelius, M; Mollnes, T E; López-Trascasa, M; van den Heuvel, L P; Goodship, T H; Marchbank, K J; Okroj, M

2014-10-01

Complement convertases are enzymatic complexes that play a central role in sustaining and amplification of the complement cascade. Impairment of complement function leads directly or indirectly to pathological conditions, including higher infection rate, kidney diseases, autoimmune- or neurodegenerative diseases and ischaemia-reperfusion injury. An assay for direct measurement of activity of the convertases in patient sera is not available. Existing assays testing convertase function are based on purified complement components and, thus, convertase formation occurs under non-physiological conditions. We designed a new assay, in which C5 blocking compounds enabled separation of the complement cascade into two phases: the first ending at the stage of C5 convertases and the second ending with membrane attack complex formation. The use of rabbit erythrocytes or antibody-sensitized sheep erythrocytes as the platforms for convertase formation enabled easy readout based on measurement of haemolysis. Thus, properties of patient sera could be studied directly regarding convertase activity and membrane attack complex formation. Another advantage of this assay was the possibility to screen for host factors such as C3 nephritic factor and other anti-complement autoantibodies, or gain-of-function mutations, which prolong the half-life of complement convertases. Herein, we present proof of concept, detailed description and validation of this novel assay. © 2014 British Society for Immunology.

Proprotein Convertases in Human Breast Cancer

Science.gov (United States)

2001-03-01

virgin mouse mammary glands (although further increase occurs during pregancy and lactation), a finding that is consistent with the fact that the MMTV-LTR...mM nude mice in response to estrogen and the NaC1, sodium deoxycholate (0-5%), SDS (0-1%), antiestrogen tamoxifen. NP40 (0-5%) and 100kIU/ml Trasylol

Plasma lipoprotein(a) levels in patients with homozygous autosomal dominant hypercholesterolemia

NARCIS (Netherlands)

Sjouke, B.; Yahya, R.; Tanck, M.W.T.; Defesche, J.C.; Graaf, J. de; Wiegman, A.; Kastelein, J.J.; Mulder, M.T.; Hovingh, G.K.; Roeters van Lennep, J.E.

2017-01-01

BACKGROUND: Patients with autosomal dominant hypercholesterolemia (ADH), caused by mutations in either low-density lipoprotein receptor (LDLR), apolipoprotein B (APOB), or proprotein convertase subtilisin-kexin type 9 (PCSK9) are characterized by high low-density lipoprotein cholesterol levels and

Plasma lipoprotein(a) levels in patients with homozygous autosomal dominant hypercholesterolemia

NARCIS (Netherlands)

Sjouke, Barbara; Yahya, Reyhana; Tanck, Michael W. T.; Defesche, Joep C.; de Graaf, Jacqueline; Wiegman, Albert; Kastelein, John J. P.; Mulder, Monique T.; Hovingh, G. Kees; Roeters van Lennep, Jeanine E.

2017-01-01

Patients with autosomal dominant hypercholesterolemia (ADH), caused by mutations in either low-density lipoprotein receptor (LDLR), apolipoprotein B (APOB), or proprotein convertase subtilisin-kexin type 9 (PCSK9) are characterized by high low-density lipoprotein cholesterol levels and in some

The mechanism by which a propeptide-encoded pH sensor regulates spatiotemporal activation of furin.

Science.gov (United States)

Williamson, Danielle M; Elferich, Johannes; Ramakrishnan, Parvathy; Thomas, Gary; Shinde, Ujwal

2013-06-28

The proprotein convertase furin requires the pH gradient of the secretory pathway to regulate its multistep, compartment-specific autocatalytic activation. Although His-69 within the furin prodomain serves as the pH sensor that detects transport of the propeptide-enzyme complex to the trans-Golgi network, where it promotes cleavage and release of the inhibitory propeptide, a mechanistic understanding of how His-69 protonation mediates furin activation remains unclear. Here we employ biophysical, biochemical, and computational approaches to elucidate the mechanism underlying the pH-dependent activation of furin. Structural analyses and binding experiments comparing the wild-type furin propeptide with a nonprotonatable His-69 → Leu mutant that blocks furin activation in vivo revealed protonation of His-69 reduces both the thermodynamic stability of the propeptide as well as its affinity for furin at pH 6.0. Structural modeling combined with mathematical modeling and molecular dynamic simulations suggested that His-69 does not directly contribute to the propeptide-enzyme interface but, rather, triggers movement of a loop region in the propeptide that modulates access to the cleavage site and, thus, allows for the tight pH regulation of furin activation. Our work establishes a mechanism by which His-69 functions as a pH sensor that regulates compartment-specific furin activation and provides insights into how other convertases and proteases may regulate their precise spatiotemporal activation.

The Mechanism by Which a Propeptide-encoded pH Sensor Regulates Spatiotemporal Activation of Furin*

Science.gov (United States)

Williamson, Danielle M.; Elferich, Johannes; Ramakrishnan, Parvathy; Thomas, Gary; Shinde, Ujwal

2013-01-01

The proprotein convertase furin requires the pH gradient of the secretory pathway to regulate its multistep, compartment-specific autocatalytic activation. Although His-69 within the furin prodomain serves as the pH sensor that detects transport of the propeptide-enzyme complex to the trans-Golgi network, where it promotes cleavage and release of the inhibitory propeptide, a mechanistic understanding of how His-69 protonation mediates furin activation remains unclear. Here we employ biophysical, biochemical, and computational approaches to elucidate the mechanism underlying the pH-dependent activation of furin. Structural analyses and binding experiments comparing the wild-type furin propeptide with a nonprotonatable His-69 → Leu mutant that blocks furin activation in vivo revealed protonation of His-69 reduces both the thermodynamic stability of the propeptide as well as its affinity for furin at pH 6.0. Structural modeling combined with mathematical modeling and molecular dynamic simulations suggested that His-69 does not directly contribute to the propeptide-enzyme interface but, rather, triggers movement of a loop region in the propeptide that modulates access to the cleavage site and, thus, allows for the tight pH regulation of furin activation. Our work establishes a mechanism by which His-69 functions as a pH sensor that regulates compartment-specific furin activation and provides insights into how other convertases and proteases may regulate their precise spatiotemporal activation. PMID:23653353

Cardiovascular Efficacy and Safety of Bococizumab in High-Risk Patients

DEFF Research Database (Denmark)

Ridker, Paul M; Revkin, James; Amarenco, Pierre

2017-01-01

BACKGROUND: Bococizumab is a humanized monoclonal antibody that inhibits proprotein convertase subtilisin-kexin type 9 (PCSK9) and reduces levels of low-density lipoprotein (LDL) cholesterol. We sought to evaluate the efficacy of bococizumab in patients at high cardiovascular risk. METHODS: In tw...

Efficacy and Safety of Alirocumab in Reducing Lipids and Cardiovascular Events

NARCIS (Netherlands)

Robinson, Jennifer G.; Farnier, Michel; Krempf, Michel; Bergeron, Jean; Luc, Gérald; Averna, Maurizio; Stroes, Erik S.; Langslet, Gisle; Raal, Frederick J.; El Shahawy, Mahfouz; Koren, Michael J.; Lepor, Norman E.; Lorenzato, Christelle; Pordy, Robert; Chaudhari, Umesh; Kastelein, John J. P.; Caccavo, Alberto; Codutti, Oscar; Gelersztein, Elisabeth; Vico, Marisa; Zaidman, Cesar; Majul, Claudio; Balthazar, Yohan; Capiau, Luc; Vrolix, Mathias; Vermeersch, Paul; Gotchev, Dobromir; Todorov, Georgi; Tumbev, Haralin; Tzekova, Maria; Gronkova, Naydenka; Dimov, Bojidar; Nikolaeva, Antonoaneta; Devedzhiev, Tsvetan; Mincheva, Valentina; D'Ignazio, Giuseppe; Dzongowski, Peter; Elliott, Thomas; Hart, Randy; Hoag, Gordon; Martinho, Valdemar; O'Mahony, Michael; Tellier, Guy; Pandey, Shekhar; Heaton, Kenneth; Constance, Christian; Phaneuf, Denis-Carl; Shu, Daniel; Narvaez, Nancy Cardenas; Cañon, Claudia Olivares

2015-01-01

BACKGROUND Alirocumab, a monoclonal antibody that inhibits proprotein convertase subtilisin-kexin type 9 (PCSK9), has been shown to reduce low-density lipoprotein (LDL) cholesterol levels in patients who are receiving statin therapy. Larger and longer-term studies are needed to establish safety and

PCSK9 inhibition fails to alter hepatic LDLR, circulating cholesterol, and atherosclerosis in the absence of ApoE

NARCIS (Netherlands)

Ason, B.; Hoorn, J.W.A. van der; Chan, J.; Lee, E.; Pieterman, E.J.; Nguyen, K.K.; Di, M.; Shetterly, S.; Tang, J.; Yeh, W.C.; Schwarz, M.; Jukema, J.W.; Scott, R.; Wasserman, S.M.; Princen, H.M.G.; Jackson, S.

2014-01-01

LDL cholesterol (LDL-C) contributes to coronary heart disease. Proprotein convertase subtilisin/kexin type 9 (PCSK9) increases LDL-C by inhibiting LDL-C clearance. The therapeutic potential for PCSK9 inhibitors is highlighted by the fact that PCSK9 loss-of-function carriers exhibit 15-30% lower

The PCSK9 decade

NARCIS (Netherlands)

Lambert, Gilles; Sjouke, Barbara; Choque, Benjamin; Kastelein, John J. P.; Hovingh, G. Kees

2012-01-01

PCSK9 proprotein convertase subtilisin/kexin type (PCSK9) is a crucial protein in LDL cholesterol (LDL-C) metabolism by virtue of its pivotal role in the degradation of the LDL receptor. In recent years, both in vitro and in vivo studies have greatly supplemented our understanding of the (patho)

Identifying low density lipoprotein cholesterol associated variants in the Annexin A2 (ANXA2) gene

DEFF Research Database (Denmark)

Fairoozy, Roaa Hani; Cooper, Jackie; White, Jon

2017-01-01

Background and aims: Annexin-A2 (AnxA2) is an endogenous inhibitor of proprotein convertase subtilisin/kexin type-9 (PCSK9). The repeat-one (R1) domain of AnxA2 binds to PCSK9, blocking its ability to promote degradation of low-density lipoprotein cholesterol-receptors (LDL-R) and thereby regulat...

Genetic variation at the PCSK9 locus, low density lipoproteins, response to pravastatin and coronary heart disease: results from PROSPER

Science.gov (United States)

Caucasian carriers of the T allele at R46L in the proprotein convertase subtilisin/kexin type 9 (PCSK9) locus have been reported to have 15% lower low-density lipoprotein (LDL) cholesterol (C) levels and 47% lower coronary heart disease (CHD) risk. Our objective was to examine two PCSK9 single nucle...

Exome sequencing finds a novel PCSK1 mutation in a child with generalized malabsorptive diarrhea and diabetes insipidus.

Science.gov (United States)

Yourshaw, Michael; Solorzano-Vargas, R Sergio; Pickett, Lindsay A; Lindberg, Iris; Wang, Jiafang; Cortina, Galen; Pawlikowska-Haddal, Anna; Baron, Howard; Venick, Robert S; Nelson, Stanley F; Martín, Martín G

2013-12-01

Congenital diarrhea disorders are a group of genetically diverse and typically autosomal recessive disorders that have yet to be well characterized phenotypically or molecularly. Diagnostic assessments are generally limited to nutritional challenges and histologic evaluation, and many subjects eventually require a prolonged course of intravenous nutrition. Here we describe next-generation sequencing techniques to investigate a child with perplexing congenital malabsorptive diarrhea and other presumably unrelated clinical problems; this method provides an alternative approach to molecular diagnosis. We screened the diploid genome of an affected individual, using exome sequencing, for uncommon variants that have observed protein-coding consequences. We assessed the functional activity of the mutant protein, as well as its lack of expression using immunohistochemistry. Among several rare variants detected was a homozygous nonsense mutation in the catalytic domain of the proprotein convertase subtilisin/kexin type 1 gene. The mutation abolishes prohormone convertase 1/3 endoprotease activity as well as expression in the intestine. These primary genetic findings prompted a careful endocrine reevaluation of the child at 4.5 years of age, and multiple significant problems were subsequently identified consistent with the known phenotypic consequences of proprotein convertase subtilisin/kexin type 1 (PCSK1) gene mutations. Based on the molecular diagnosis, alternate medical and dietary management was implemented for diabetes insipidus, polyphagia, and micropenis. Whole-exome sequencing provides a powerful diagnostic tool to clinicians managing rare genetic disorders with multiple perplexing clinical manifestations.

Genetic Rescue of Glycosylation-deficient Fgf23 in the Galnt3 Knockout Mouse

OpenAIRE

Ichikawa, Shoji; Gray, Amie K.; Padgett, Leah R.; Allen, Matthew R.; Clinkenbeard, Erica L.; Sarpa, Nicole M.; White, Kenneth E.; Econs, Michael J.

2014-01-01

Fibroblast growth factor 23 (FGF23) is a hormone that inhibits renal phosphate reabsorption and 1,25-dihydroxyvitamin D biosynthesis. The FGF23 subtilisin-like proprotein convertase recognition sequence (176RHTR179↓) is protected by O-glycosylation through ppGalNAc-T3 (GALNT3) activity. Thus, inactivating GALNT3 mutations render FGF23 susceptible to proteolysis, thereby reducing circulating intact hormone levels and leading to hyperphosphatemic familial tumoral calcinosis. To further delineat...

Thyroid hormone reduces PCSK9 and stimulates bile acid synthesis in humans[S

OpenAIRE

Bonde, Ylva; Breuer, Olof; L?tjohann, Dieter; Sj?berg, Stefan; Angelin, Bo; Rudling, Mats

2014-01-01

Reduced plasma LDL-cholesterol is a hallmark of hyperthyroidism and is caused by transcriptional stimulation of LDL receptors in the liver. Here, we investigated whether thyroid hormone (TH) actions involve other mechanisms that may also account for the reduction in LDL-cholesterol, including effects on proprotein convertase subtilisin/kexin type 9 (PCSK9) and bile acid synthesis. Twenty hyperthyroid patients were studied before and after clinical normalization, and the responses to hyperthyr...

A novel method for direct measurement of complement convertases activity in human serum

NARCIS (Netherlands)

Blom, A.M.; Volokhina, E.B.; Fransson, V.; Stromberg, P.; Berghard, L.; Viktorelius, M.; Mollnes, T.E.; Lopez-Trascasa, M.; Heuvel, B. van den; Goodship, T.H.; Marchbank, K.J.; Okroj, M.

2014-01-01

Complement convertases are enzymatic complexes that play a central role in sustaining and amplification of the complement cascade. Impairment of complement function leads directly or indirectly to pathological conditions, including higher infection rate, kidney diseases, autoimmune- or

Developmental expression of proprotein convertase 1/3 in the rat

DEFF Research Database (Denmark)

Lee, Y C; Damholt, A B; Billestrup, N

1999-01-01

demonstrated that it was relatively abundant in whole brain, lung and spleen, but not detectable in kidney, testis and heart. Using probes consisting of either the coding region or the 3' end sequences, the mRNA transcripts identified were 5.0, 3.0 and 8.5 kb. The 8.5 kb transcript detected has not been....../3 expression were detected in fetal lung, whereas low and constant expression was detected in fetal liver. Double immuno-staining showed that PC1/3 was co-localised with insulin throughout development, and at mid-gestation, PC1/3 immunoreactivity could also be detected within glucagon-producing cells...

The Crystal Structure of Cobra Venom Factor, a Cofactor for C3- and C5-Convertase CVFBb

Energy Technology Data Exchange (ETDEWEB)

Krishnan, Vengadesan; Ponnuraj, Karthe; Xu, Yuanyuan; Macon, Kevin; Volanakis, John E.; Narayana, Sthanam V.L.; (Madras); (UAB)

2009-05-26

Cobra venom factor (CVF) is a functional analog of human complement component C3b, the active fragment of C3. Similar to C3b, in human and mammalian serum, CVF binds factor B, which is then cleaved by factor D, giving rise to the CVFBb complex that targets the same scissile bond in C3 as the authentic complement convertases C4bC2a and C3bBb. Unlike the latter, CVFBb is a stable complex and an efficient C5 convertase. We solved the crystal structure of CVF, isolated from Naja naja kouthia venom, at 2.6 {angstrom} resolution. The CVF crystal structure, an intermediate between C3b and C3c, lacks the TED domain and has the CUB domain in an identical position to that seen in C3b. The similarly positioned CUB and slightly displaced C345c domains of CVF could play a vital role in the formation of C3 convertases by providing important primary binding sites for factor B.

Circumventing furin enhances factor VIII biological activity and ameliorates bleeding phenotypes in hemophilia models

OpenAIRE

Siner, Joshua I.; Samelson-Jones, Benjamin J.; Crudele, Julie M.; French, Robert A.; Lee, Benjamin J.; Zhou, Shanzhen; Merricks, Elizabeth; Raymer, Robin; Nichols, Timothy C.; Camire, Rodney M.; Arruda, Valder R.

2016-01-01

Processing by the proprotein convertase furin is believed to be critical for the biological activity of multiple proteins involved in hemostasis, including coagulation factor VIII (FVIII). This belief prompted the retention of the furin recognition motif (amino acids 1645–1648) in the design of B-domain–deleted FVIII (FVIII-BDD) products in current clinical use and in the drug development pipeline, as well as in experimental FVIII gene therapy strategies. Here, we report that processing by fu...

Payer Perspectives on PCSK9 Inhibitors: A Conversation with Stephen Gorshow, MD, and James T. Kenney, RPh, MBA.

Science.gov (United States)

Mehr, Stanton R

2016-02-01

The new proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors can have significant budget effects, depending on the breadth of the US Food and Drug Administration (FDA)'s approved labeling. American Health & Drug Benefits asked Stephen Gorshow, MD, Regional Medical Director, UnitedHealthcare, and James T. Kenney, RPh, MBA, Manager, Specialty and Pharmacy Contracts, Harvard Pilgrim Health Care, to participate in a teleconference to better understand how payers are approaching the management of these agents.

Enzyme activity assays within microstructured optical fibers enabled by automated alignment.

Science.gov (United States)

Warren-Smith, Stephen C; Nie, Guiying; Schartner, Erik P; Salamonsen, Lois A; Monro, Tanya M

2012-12-01

A fluorescence-based enzyme activity assay has been demonstrated within a small-core microstructured optical fiber (MOF) for the first time. To achieve this, a reflection-based automated alignment system has been developed, which uses feedback and piezoelectric actuators to maintain optical alignment. The auto-alignment system provides optical stability for the time required to perform an activity assay. The chosen assay is based on the enzyme proprotein convertase 5/6 (PC6) and has important applications in women's health.

Prohormone convertase 1/3 is essential for processing of the glucose-dependent insulinotropic polypeptide precursor

DEFF Research Database (Denmark)

Ugleholdt, Randi; Poulsen, Marie-Louise H; Holst, Peter J

2006-01-01

The physiology of the incretin hormones, glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), and their role in type 2 diabetes currently attract great interest. Recently we reported an essential role for prohormone convertase (PC) 1/3 in the cleavage of intesti......The physiology of the incretin hormones, glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), and their role in type 2 diabetes currently attract great interest. Recently we reported an essential role for prohormone convertase (PC) 1/3 in the cleavage....../3 is essential and sufficient for the production of the intestinal incretin hormone GIP, whereas PC2, although capable of cleaving proGIP, does not participate in intestinal proGIP processing and is not found in intestinal GIP-expressing cells....

The role of proprotein convertase subtilisin/kexin type 9 inhibitors in ...

African Journals Online (AJOL)

antioxidant. Oxidative stress is believed to be a major cause of. Abstract ... density lipoprotein (LDL), increase the risk of cardiovascular disease. Familial ..... the working group on coronary pathophysiology and microcirculation of the. European ...

Zymogen Activation and Subcellular Activity of Subtilisin Kexin Isozyme 1/Site 1 Protease*

Science.gov (United States)

da Palma, Joel Ramos; Burri, Dominique Julien; Oppliger, Joël; Salamina, Marco; Cendron, Laura; de Laureto, Patrizia Polverino; Seidah, Nabil Georges; Kunz, Stefan; Pasquato, Antonella

2014-01-01

The proprotein convertase subtilisin kexin isozyme 1 (SKI-1)/site 1 protease (S1P) plays crucial roles in cellular homeostatic functions and is hijacked by pathogenic viruses for the processing of their envelope glycoproteins. Zymogen activation of SKI-1/S1P involves sequential autocatalytic processing of its N-terminal prodomain at sites B′/B followed by the herein newly identified C′/C sites. We found that SKI-1/S1P autoprocessing results in intermediates whose catalytic domain remains associated with prodomain fragments of different lengths. In contrast to other zymogen proprotein convertases, all incompletely matured intermediates of SKI-1/S1P showed full catalytic activity toward cellular substrates, whereas optimal cleavage of viral glycoproteins depended on B′/B processing. Incompletely matured forms of SKI-1/S1P further process cellular and viral substrates in distinct subcellular compartments. Using a cell-based sensor for SKI-1/S1P activity, we found that 9 amino acid residues at the cleavage site (P1–P8) and P1′ are necessary and sufficient to define the subcellular location of processing and to determine to what extent processing of a substrate depends on SKI-1/S1P maturation. In sum, our study reveals novel and unexpected features of SKI-1/S1P zymogen activation and subcellular specificity of activity toward cellular and pathogen-derived substrates. PMID:25378398

Luteolin restricts dengue virus replication through inhibition of the proprotein convertase furin.

Science.gov (United States)

Peng, Minhua; Watanabe, Satoru; Chan, Kitti Wing Ki; He, Qiuyan; Zhao, Ya; Zhang, Zhongde; Lai, Xiaoping; Luo, Dahai; Vasudevan, Subhash G; Li, Geng

2017-07-01

In many countries afflicted with dengue fever, traditional medicines are widely used as panaceas for illness, and here we describe the systematic evaluation of a widely known natural product, luteolin, originating from the "heat clearing" class of herbs. We show that luteolin inhibits the replication of all four serotypes of dengue virus, but the selectivity of the inhibition was weak. In addition, ADE-mediated dengue virus infection of human cell lines and primary PBMCs was inhibited. In a time-of-drug-addition study, luteolin was found to reduce infectious virus particle formation, but not viral RNA synthesis, in Huh-7 cells. During the virus life cycle, the host protease furin cleaves the pr moiety from prM protein of immature virus particles in the trans-Golgi network to produce mature virions. Analysis of virus particles from luteolin-treated cells revealed that prM was not cleaved efficiently. Biochemical interrogation of human furin showed that luteolin inhibited the enzyme activity in an uncompetitive manner, with Ki value of 58.6 μM, suggesting that treatment may restrict the virion maturation process. Luteolin also exhibited in vivo antiviral activity in mice infected with DENV, causing reduced viremia. Given the mode of action of luteolin and its widespread source, it is possible that it can be tested in combination with other dengue virus inhibitors. Copyright © 2017 Elsevier B.V. All rights reserved.

Impaired intestinal proglucagon processing in mice lacking prohormone convertase 1

DEFF Research Database (Denmark)

Ugleholdt, Randi; Zhu, Xiaorong; Deacon, Carolyn F

2003-01-01

proglucagon processing showed marked defects. Tissue proglucagon levels in null mice were elevated, and proglucagon processing to glicentin, oxyntomodulin, and glucagon-like peptide-1 and -2 (GLP-1 and GLP-2) was markedly decreased, indicating that PC1 is essential for the processing of all the intestinal...... proglucagon cleavage sites. This includes the monobasic site R(77) and, thereby, production of mature, biologically active GLP-1. We also found elevated glucagon levels, suggesting that factors other than PC1 that are capable of processing to mature glucagon are present in the secretory granules of the L cell......The neuroendocrine prohormone convertases 1 and 2 (PC1 and PC2) are expressed in endocrine intestinal L cells and pancreatic A cells, respectively, and colocalize with proglucagon in secretory granules. Mice lacking PC2 have multiple endocrinopathies and cannot process proglucagon to mature...

The structure of C2b, a fragment of complement component C2 produced during C3 convertase formation

Energy Technology Data Exchange (ETDEWEB)

Krishnan, Vengadesan [Center for Biophysical Sciences and Engineering, School of Optometry, University of Alabama at Birmingham, Birmingham, AL 35294 (United States); Xu, Yuanyuan [Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, AL 35294 (United States); Macon, Kevin [Center for Biophysical Sciences and Engineering, School of Optometry, University of Alabama at Birmingham, Birmingham, AL 35294 (United States); Volanakis, John E. [Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294 (United States); Narayana, Sthanam V. L., E-mail: narayana@uab.edu [Center for Biophysical Sciences and Engineering, School of Optometry, University of Alabama at Birmingham, Birmingham, AL 35294 (United States)

2009-03-01

The crystal structure of C2b has been determined at 1.8 Å resolution, which reveals the arrangement of its three complement control protein (CCP) modules. A model for complement component C2 is presented and its conformational changes during the C3-convertase formation are also discussed. The second component of complement (C2) is a multi-domain serine protease that provides catalytic activity for the C3 and C5 convertases of the classical and lectin pathways of human complement. The formation of these convertases requires the Mg{sup 2+}-dependent binding of C2 to C4b and the subsequent cleavage of C2 by C1s or MASP2, respectively. The crystal structure of full-length C2 is not yet available, although the structure of its C-terminal catalytic segment C2a has been determined. The crystal structure of the N-terminal segment C2b of C2 determined to 1.8 Å resolution presented here reveals the arrangement of its three CCP domains. The domains are arranged differently compared with most other CCP-domain assemblies, but their arrangement is similar to that found in the Ba part of the full-length factor B structure. The crystal structures of C2a, C2b and full-length factor B are used to generate a model for C2 and a discussion of the domain association and possible interactions with C4b during formation of the C4b–C2 complex is presented. The results of this study also suggest that upon cleavage by C1s, C2a domains undergo conformational rotation while bound to C4b and the released C2b domains may remain folded together similar to as observed in the intact protein.

The structure of C2b, a fragment of complement component C2 produced during C3 convertase formation

International Nuclear Information System (INIS)

Krishnan, Vengadesan; Xu, Yuanyuan; Macon, Kevin; Volanakis, John E.; Narayana, Sthanam V. L.

2009-01-01

The crystal structure of C2b has been determined at 1.8 Å resolution, which reveals the arrangement of its three complement control protein (CCP) modules. A model for complement component C2 is presented and its conformational changes during the C3-convertase formation are also discussed. The second component of complement (C2) is a multi-domain serine protease that provides catalytic activity for the C3 and C5 convertases of the classical and lectin pathways of human complement. The formation of these convertases requires the Mg 2+ -dependent binding of C2 to C4b and the subsequent cleavage of C2 by C1s or MASP2, respectively. The crystal structure of full-length C2 is not yet available, although the structure of its C-terminal catalytic segment C2a has been determined. The crystal structure of the N-terminal segment C2b of C2 determined to 1.8 Å resolution presented here reveals the arrangement of its three CCP domains. The domains are arranged differently compared with most other CCP-domain assemblies, but their arrangement is similar to that found in the Ba part of the full-length factor B structure. The crystal structures of C2a, C2b and full-length factor B are used to generate a model for C2 and a discussion of the domain association and possible interactions with C4b during formation of the C4b–C2 complex is presented. The results of this study also suggest that upon cleavage by C1s, C2a domains undergo conformational rotation while bound to C4b and the released C2b domains may remain folded together similar to as observed in the intact protein

Sensitive radiometric assay for enkephalin convertase and other carboxypeptidase B-like enzymes

International Nuclear Information System (INIS)

Stack, G.; Fricker, L.D.; Snyder, S.H.

1984-01-01

A sensitive radiometric assay for carboxypeptidase B-like enzymes has been developed using enkephalin convertase, an enkephalin synthesizing carboxypeptidase. The assay is based on the differential solubility of 3 H-labeled substrate and product in chloroform. The substrates 3 H-benzoyl-Phe-Ala-Arg or 3 H-benzoyl-Phe-Leu-Arg are poorly soluble in chloroform due to the charged arginine. The products of carboxypeptidase B-like activity on these substrates, 3 H-benzoyl-Phe-Ala or 3 H-benzoyl Phe-Leu partition quantitatively into chloroform, allowing rapid separation of product from substrate. This assay is approximately 100 times more sensitive than a similar fluorometric assay utilizing dansyl-Phe-Ala-Arg as a substrate

Sensitive radiometric assay for enkephalin convertase and other carboxypeptidase B-like enzymes

Energy Technology Data Exchange (ETDEWEB)

Stack, G.; Fricker, L.D.; Snyder, S.H.

1984-01-09

A sensitive radiometric assay for carboxypeptidase B-like enzymes has been developed using enkephalin convertase, an enkephalin synthesizing carboxypeptidase. The assay is based on the differential solubility of /sup 3/H-labeled substrate and product in chloroform. The substrates /sup 3/H-benzoyl-Phe-Ala-Arg or /sup 3/H-benzoyl-Phe-Leu-Arg are poorly soluble in chloroform due to the charged arginine. The products of carboxypeptidase B-like activity on these substrates, /sup 3/H-benzoyl-Phe-Ala or /sup 3/H-benzoyl Phe-Leu partition quantitatively into chloroform, allowing rapid separation of product from substrate. This assay is approximately 100 times more sensitive than a similar fluorometric assay utilizing dansyl-Phe-Ala-Arg as a substrate.

Cardiology update 2017: The first quarter

Directory of Open Access Journals (Sweden)

Sridharan Umapathy

2017-01-01

Full Text Available In the first quarter of 2017, proprotein convertase subtilisin/kexin type 9's role got defined further with a number of trials such as FOURIER, ORION-1, and SPIRE 1 and 2. TAVI proves safe in intermediate-risk patients in the Surgical Replacement and Transcatheter Aortic Valve Implantation study. Newer anticoagulants extended their role to valvular heart disease. Bioabsorbable stent showed problems (ABSORB 2 and 3. New guidelines have been released for syncope and transcatheter aortic valve replacement implantation. Clinical outcome studies involving instantaneous wave-free ratio (IFR showed IFR to be noninferior to fractional flow reserve. Optimal medical therapy proves noninferior to percutaneous coronary intervention in single vessel chronic total occlusion.

Molecular cloning and characterization of prohormone convertase 1 gene in abalone (Haliotis diversicolor supertexta).

Science.gov (United States)

Zhou, Jin; Cai, Zhong-hua

2010-03-01

Prohormone convertases (PCs) are calcium-dependent serine endoproteases of the subtilisin family that play a key role in the posttranslational processing of precursors for bioactive peptides. In this study, the cDNA of PC1 from abalone (Haliotis diversicolor supertexta) was cloned and sequenced. The PC1 cDNA consisted of 2216 bp with an open reading frame of 2010 bp encoding a 670 amino acid peptide. Comparative structural analysis revealed that abalone PC1 shared high similarity and identity with most PC counterparts. The profile of deduced peptide of PC1 was composed of an N-terminal signal peptide, a prosegment domain, a catalytic domain and a P domain, which were common in many species. Sequence analysis indicated that the abalone PC1 was highly conserved in catalytic domain, including three conserved serine catalytic signatures that comprised a catalytic triad active center. Also conserved were the potential cleavage site for release of the mature peptide, a cognate integrin binding site RGD in P domain, and four cysteine residues involved in forming an intrachain disulfide bridge. To further investigate the functions of PC1 in abalone, real-time quantitative PCR was performed to determine the expression level of this gene at three different reproduction stages (i.e. pre-, during- and post-breeding). Results indicated that PC1 was expressed throughout the three stages but the expression levels varied with the timepoints and different tissues in abalone. The expression levels of PC1 in digestive gland were much higher than those of the gonad. In female abalone, the expression of PC1 was higher at pre-breeding and during-breeding stages (Pabalone reproduction process (e.g. spawning or sperming). PC1 is a potential prohormone processing enzyme and it may play a critical role in abalone physiological processes related to reproduction. 2009 Elsevier Inc. All rights reserved.

[PCSK-9 inhibitors, effects on LDL-C and future implications: What you should know].

Science.gov (United States)

Corral, P; Ruiz, A J

The discovery of proprotein convertase subtilisin/kexin type 9 (PCSK9) in 2003 in families with familial hypercholesterolemia (HF) later generated the development of pharmacological strategies in order to inhibit this protein. Twelve years after this discovery, the first two biological compounds (monoclonal antibodies) were approved, which have been shown to substantially decrease LDL-C and other lipid subfractions. The objective of the present article is to review the history of the discovery of PCSK9, its physiology and pathophysiology and subsequent pharmacological development. The objectives and goals reached to date and the pending questions regarding the efficacy and safety of its clinical use are presented. Copyright © 2017 SEH-LELHA. Publicado por Elsevier España, S.L.U. All rights reserved.

Developmentally regulated expression by Trypanosoma cruzi of molecules that accelerate the decay of complement C3 convertases

International Nuclear Information System (INIS)

Rimoldi, M.T.; Sher, A.; Heiny, A.; Lituchy, A.; Hammer, C.H.; Joiner, K.

1988-01-01

The authors recently showed that culture-derived metacyclic trypomastigotes (CMT), but not epimastigotes (Epi), of the Miranda 99 strain of Trypanosoma cruzi evade lysis by the human alternative complement pathway because of inefficient binding of factor B to complement component C3b on the parasite surface. These results suggested that CMT and tissue-culture-derived trypomastigotes (TCT), which also activate the alternative pathway poorly, might produce a molecule capable of interfering with factor B binding to C3b. They now demonstrate that CMT and TCT lysates, as well as molecules spontaneously shed from CMT and TCT but not Epi, accelerate decay of 125 I-labeled factor Bb from the alternative-pathway C3 convertase (C3bBb) assembled on zymosan or Epi and also accelerate decay of the classical-pathway C3 convertase (C4b2a) on sheep erythrocytes. Parasites metabolically labeled with [ 35 S]methionine spontaneously shed a limited number of radioactive components, ranging in molecular mass from 86 to 155 kDa for trypomastigotes and 25 to 80 kDa for Epi. Decay-accelerating activity within supernatants is inactivated by papain and is coeluted with 35 S-containing polypeptides on FPLC anion-exchange chromatography, suggesting that the active constituents are protein molecules. Molecules with decay-accelerating activity may explain the developmentally regulated resistance to complement-mediated lysis in infective and vertebrate stages for T. cruzi life cycle

Effects of MAT9001 containing eicosapentaenoic acid and docosapentaenoic acid, compared to eicosapentaenoic acid ethyl esters, on triglycerides, lipoprotein cholesterol, and related variables.

Science.gov (United States)

Maki, Kevin C; Bobotas, George; Dicklin, Mary R; Huebner, Margie; Keane, William F

Long-chain omega-3 fatty acid concentrate pharmaceuticals are used in the United States for treatment of severe hypertriglyceridemia (≥500 mg/dL) and are under investigation as adjuncts to statins for lowering cardiovascular risk in patients with high triglycerides (TGs; 200-499 mg/dL). To evaluate MAT9001, an investigational prescription-only omega-3 fatty acid agent containing predominantly eicosapentaenoic acid (EPA) and docosapentaenoic acid, in 42 men and women with fasting TG 200 to 400 mg/dL. In this open-label, crossover trial, subjects received MAT9001 and EPA ethyl esters (EPA-EE) in random order. They were housed in a clinical research unit for 2 14-day treatment periods, separated by a ≥35-day washout. Lipoprotein lipids, apolipoproteins (Apos) and proprotein convertase subtilisin kexin type 9 levels were measured before and at the end of each treatment period. MAT9001, compared with EPA-EE, resulted in significantly (P < .05) larger reductions from pretreatment levels for TG (-33.2% vs -10.5%), total cholesterol (-9.0% vs -6.2%), non-high-density lipoprotein cholesterol (-8.8% vs -4.6%), very low-density lipoprotein cholesterol (-32.5% vs -8.1%), Apo C3 (-25.5% vs -5.0%), and proprotein convertase subtilisin kexin type 9 (-12.3% vs +8.8%). MAT9001 also produced a significantly (P = .003) larger reduction in Apo A1 (-15.3% vs -10.2%), but responses for high-density lipoprotein cholesterol (-11.3% vs -11.1%), low-density lipoprotein cholesterol (-2.4% vs -4.3%), and Apo B (-3.8% vs -0.7%), respectively, were not significantly different relative to EPA-EE. MAT9001 produced significantly larger reductions than EPA-EE in several lipoprotein-related variables that would be expected to favorably alter cardiovascular disease risk in men and women with hypertriglyceridemia. Copyright © 2016 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Cooperation between MASP-1 and MASP-2 in the generation of C3 convertase through the MBL pathway

DEFF Research Database (Denmark)

Møller-Kristensen, Mette; Thiel, Steffen; Sjöholm, Anders

2007-01-01

The complement system is an important part of the innate immune system. Three pathways, the classical, the alternative and the lectin pathway, lead to the cleavage of complement factor C3, a central event in the activation of the complement system. We investigated the deposition of C3b (solid-pha....... Our results demonstrate a function of the orphan protease MASP-1 by providing evidence that this enzyme collaborates with MASP-2 in the generation of C3 convertase, a process observable at high serum concentration, but not at low serum concentration...

The fsr Quorum-Sensing System and Cognate Gelatinase Orchestrate the Expression and Processing of Proprotein EF_1097 into the Mature Antimicrobial Peptide Enterocin O16.

Science.gov (United States)

Dundar, Halil; Brede, Dag A; La Rosa, Sabina Leanti; El-Gendy, Ahmed Osama; Diep, Dzung B; Nes, Ingolf F

2015-07-01

A novel antimicrobial peptide designated enterocin O16 was purified from Enterococcus faecalis. Mass spectrometry showed a monoisotopic mass of 7,231 Da, and N-terminal Edman degradation identified a 29-amino-acid sequence corresponding to residues 90 to 119 of the EF_1097 protein. Bioinformatic analysis showed that enterocin O16 is composed of the 68 most C-terminal residues of the EF_1097 protein. Introduction of an in-frame isogenic deletion in the ef1097 gene abolished the production of enterocin O16. Enterocin O16 has a narrow inhibitory spectrum, as it inhibits mostly lactobacilli. Apparently, E. faecalis is intrinsically resistant to the antimicrobial peptide, as no immunity connected to the production of enterocin O16 could be identified. ef1097 has previously been identified as one of three loci regulated by the fsr quorum-sensing system. The introduction of a nonsense mutation into fsrB consistently impaired enterocin O16 production, but externally added gelatinase biosynthesis-activating pheromone restored the antimicrobial activity. Functional genetic analysis showed that the EF_1097 proprotein is processed extracellularly into enterocin O16 by the metalloprotease GelE. Thus, it is evident that the fsr quorum-sensing system constitutes the regulatory unit that controls the expression of the EF_1097 precursor protein and the protease GelE and that the latter is required for the formation of enterocin O16. On the basis of these results, this study identified antibacterial antagonism as a novel aspect related to the function of fsr and provides a rationale for why ef1097 is part of the fsr regulon. The fsr quorum-sensing system modulates important physiological functions in E. faecalis via the activity of GelE. The present study presents a new facet of fsr signaling. The system controls the expression of three primary target operons (fsrABCD, gelE-sprE, and ef1097-ef1097b). We demonstrate that the concerted expression of these operons constitutes the

Chemical structure and properties of low-molecular furin inhibitors

Directory of Open Access Journals (Sweden)

T. V. Osadchuk

2016-12-01

Full Text Available The review is devoted to the analysis of the relationship between a chemical structure and properties of low-molecular weight inhibitors of furin, the most studied proprotein convertase, which is involved in the development of some pathologies, such as oncologic diseases, viral and bacterial infections, etc. The latest data concerning the influence of peptides, pseudo-peptides, aromatic and heterocyclic compounds, some natural ones such as flavonoids, coumarins, and others on enzyme inactivation are considered. The power of furin inhibition is shown to rise with the increasing number of positively charged groups in the structure of these compounds. Peptidomimetics (Ki = 5-8 pM are shown to be the most effective furin inhibitors. The synthesized substances, however, have not been used in practical application yet. Nowadays it is very important to find more selective inhibitors, improve their stability, bioavailability and safety for the human organism.

PCSK9: From Basic Science Discoveries to Clinical Trials.

Science.gov (United States)

Shapiro, Michael D; Tavori, Hagai; Fazio, Sergio

2018-05-11

Unknown 15 years ago, PCSK9 (proprotein convertase subtilisin/kexin type 9) is now common parlance among scientists and clinicians interested in prevention and treatment of atherosclerotic cardiovascular disease. What makes this story so special is not its recent discovery nor the fact that it uncovered previously unknown biology but rather that these important scientific insights have been translated into an effective medical therapy in record time. Indeed, the translation of this discovery to novel therapeutic serves as one of the best examples of how genetic insights can be leveraged into intelligent target drug discovery. The PCSK9 saga is unfolding quickly but is far from complete. Here, we review major scientific understandings as they relate to the role of PCSK9 in lipoprotein metabolism and atherosclerotic cardiovascular disease and the impact that therapies designed to inhibit its action are having in the clinical setting. © 2018 American Heart Association, Inc.

Spatiotemporal expression of endogenous opioid processing enzymes in mouse uterus at peri-implantation.

Science.gov (United States)

Wu, Weiwei; Kong, Shuangbo; Wang, Bingyan; Chen, Yongjie; Wang, Haibin

2016-02-01

Successful implantation requires intimate interactions between a competent blastocyst and a receptive uterus. We recently demonstrated that the aberrant activation of opioid signaling by exogenous ligands adversely affects preimplantation embryonic development and subsequent implantation in mice. However, the underlying machinery governing the dynamic homeostasis of the endogenous opioid system in the uterus during early pregnancy remains elusive. We now show that all three major endogenous opioid precursors are spatiotemporally expressed in the uterus during early pregnancy. Moreover, we observe the well-coordinated expression of the synthetic enzyme prohormone convertases 1/3 (PC1/3) at lower levels and of its inhibitor proprotein convertase subtilisin/kexin type 1 inhibitor (Pcsk1n) and the degrading enzyme membrane metallo-endopeptidase (MME) at higher levels in the receptive uterus. Both estrogen and progestin tend to reduce the uterine levels of opioid ligand precursors in the ovariectomized mouse model. This tight regulation of the endogenous opioid system by PC1/3, Pcsk1n and MME has been further confirmed in physiologically related pseudopregnancy and delayed implantation mouse models. The coordinated regulation of opioid precursor biosynthesis and metabolism helps to create appropriate opioid signaling ensuring uterine receptivity for implantation. Thus, endogenous uterine opioid levels are primarily determined by the coordinated expressions of PC1/3, Pcsk1n and MME under the influence of ovarian progestin and estrogen. Our findings raise an additional cautionary note regarding the effects of opioid abuse on early pregnancy events.

Furin is a chemokine-modifying enzyme: in vitro and in vivo processing of CXCL10 generates a C-terminally truncated chemokine retaining full activity.

Science.gov (United States)

Hensbergen, Paul J; Verzijl, Dennis; Balog, Crina I A; Dijkman, Remco; van der Schors, Roel C; van der Raaij-Helmer, Elizabeth M H; van der Plas, Mariena J A; Leurs, Rob; Deelder, André M; Smit, Martine J; Tensen, Cornelis P

2004-04-02

Chemokines comprise a class of structurally related proteins that are involved in many aspects of leukocyte migration under basal and inflammatory conditions. In addition to the large number of genes, limited processing of these proteins by a variety of enzymes enhances the complexity of the total spectrum of chemokine variants. We have recently shown that the native chemokine CXCL10 is processed at the C terminus, thereby shedding the last four amino acids. The present study was performed to elucidate the mechanism in vivo and in vitro and to study the biological activity of this novel isoform of CXCL10. Using a combination of protein purification and mass spectrometric techniques, we show that the production of C-terminally truncated CXCL10 by primary keratinocytes is inhibited in vivo by a specific inhibitor of pro-protein convertases (e.g. furin) but not by inhibition of matrix metalloproteinases. Moreover, CXCL10 is processed by furin in vitro, which is abrogated by a mutation in the furin recognition site. Using GTPgammaS binding, Ca(2+) mobilization, and chemotaxis assays, we demonstrate that the C-terminally truncated CXCL10 variant is a potent ligand for CXCR3. Moreover, the inverse agonist activity on the virally encoded receptor ORF74 and the direct antibacterial activity of CXCL10 are fully retained. Hence, we have identified furin as a novel chemokine-modifying enzyme in vitro and most probably also in vivo, generating a C-terminally truncated CXCL10, which fully retains its (inverse) agonistic properties.

PCSK9: Regulation and Target for Drug Development for Dyslipidemia.

Science.gov (United States)

Burke, Amy C; Dron, Jacqueline S; Hegele, Robert A; Huff, Murray W

2017-01-06

Proprotein convertase subtilisin/kexin type-9 (PCSK9) is a secreted zymogen expressed primarily in the liver. PCSK9 circulates in plasma, binds to cell surface low-density lipoprotein (LDL) receptors, is internalized, and then targets the receptors to lysosomal degradation. Studies of naturally occurring PCSK9 gene variants that caused extreme plasma LDL cholesterol (LDL-C) deviations and altered atherosclerosis risk unleashed a torrent of biological and pharmacological research. Rapid progress in understanding the physiological regulation of PCSK9 was soon translated into commercially available biological inhibitors of PCSK9 that reduced LDL-C levels and likely also cardiovascular outcomes. Here we review the swift evolution of PCSK9 from novel gene to drug target, to animal and human testing, and finally to outcome trials and clinical applications. In addition, we explore how the genetics-guided path to PCSK9 inhibitor development exemplifies a new paradigm in pharmacology. Finally, we consider some potential challenges as PCSK9 inhibition becomes established in the clinic.

Rational Design of a Highly Potent and Selective Peptide Inhibitor of PACE4 by Salt Bridge Interaction with D160 at Position P3.

Science.gov (United States)

Dianati, Vahid; Shamloo, Azar; Kwiatkowska, Anna; Desjardins, Roxane; Soldera, Armand; Day, Robert; Dory, Yves L

2017-08-08

PACE4, a member of the proprotein convertases (PCs) family of serine proteases, is a validated target for prostate cancer. Our group has developed a potent and selective PACE4 inhibitor: Ac-LLLLRVKR-NH 2 . In seeking for modifications to increase the selectivity of this ligand toward PACE4, we replaced one of its P3 Val methyl groups with a basic group capable of forming a salt bridge with D160 of PACE4. The resulting inhibitor is eight times more potent than the P3 Val parent inhibitor and two times more selective over furin, because the equivalent salt bridge with furin E257 is not optimal. Moreover, the β-branched nature of the new P3 residue favors the extended β-sheet conformation usually associated with substrates of proteases. This work provides new insight for better understanding of β-sheet backbone-backbone interactions between serine proteases and their peptidic ligands. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

PCSK9 Inhibitors: Treating the Right Patients in Daily Practice.

Science.gov (United States)

King, Peta; Nicholls, Stephen J

2017-08-01

Monoclonal antibodies that inhibit proprotein convertase subtilisin/kexin type 9 (PCSK9) have emerged as a novel approach to low-density lipoprotein cholesterol (LDL-C) lowering. The potential role of PCSK9 inhibitors in clinical practice will be reviewed. Clinical trials have demonstrated that PCSK9 inhibitors produce robust LDL-C lowering when administered either as monotherapy or in combination with statins. This provides the opportunity to achieve effective lipid lowering in familial hypercholesterolemia, patients with either established atherosclerotic cardiovascular disease or high risk primary prevention and an important opportunity to treat patients with statin intolerance. The findings from plaque imaging and patients with established atherosclerotic cardiovascular disease suggest that PCSK9 inhibition has favorable outcomes beyond improving lipid profiles, which has the opportunity to expand their use. PCSK9 inhibitors represent a new approach to achieving effective cardiovascular risk reduction in a broader number of patients. How these agents will be taken up in clinical practice remains to be determined.

A Quantitative Systems Pharmacology Platform to Investigate the Impact of Alirocumab and Cholesterol-Lowering Therapies on Lipid Profiles and Plaque Characteristics

Directory of Open Access Journals (Sweden)

Jeffrey E Ming

2017-06-01

Full Text Available Reduction in low-density lipoprotein cholesterol (LDL-C is associated with decreased risk for cardiovascular disease. Alirocumab, an antibody to proprotein convertase subtilisin/kexin type 9 (PCSK9, significantly reduces LDL-C. Here, we report development of a quantitative systems pharmacology (QSP model integrating peripheral and liver cholesterol metabolism, as well as PCSK9 function, to examine the mechanisms of action of alirocumab and other lipid-lowering therapies, including statins. The model predicts changes in LDL-C and other lipids that are consistent with effects observed in clinical trials of single or combined treatments of alirocumab and other treatments. An exploratory model to examine the effects of lipid levels on plaque dynamics was also developed. The QSP platform, on further development and qualification, may support dose optimization and clinical trial design for PCSK9 inhibitors and lipid-modulating drugs. It may also improve our understanding of factors affecting therapeutic responses in different phenotypes of dyslipidemia and cardiovascular disease.

PCSK9 R46L Loss-of-Function Mutation Reduces Lipoprotein(a), LDL Cholesterol, and Risk of Aortic Valve Stenosis

DEFF Research Database (Denmark)

Langsted, Anne; Nordestgaard, Børge; Benn, Marianne

2016-01-01

CONTEXT: Novel, low-density lipoprotein (LDL) cholesterol-lowering proprotein convertase subtilisin/kexin type-9 (PCSK9) inhibitors also lower lipoprotein(a) levels, but the effect on aortic valve stenosis and myocardial infarction is unknown. OBJECTIVE: We tested the hypothesis that the PCSK9 R46L...... individuals of Danish descent. PARTICIPANTS: We studied 103 083 individuals from the Copenhagen General Population Study, the Copenhagen City Heart Study, and the Copenhagen Ischemic Heart Disease Study. MAIN OUTCOME MEASURES: Lipoprotein(a), LDL cholesterol, and PCSK9 R46L genotype and diagnoses of aortic...... P = .02). The corresponding values for LDL cholesterol levels were 124 (101-147) mg/dl, 104 (85-132) mg/dl, and 97 (85-128) mg/dl, respectively (trend P = 2 × 10(-52)). PCSK9 R46L carriers vs noncarriers had an age- and sex-adjusted odds ratio of 0.64 (95% confidence interval, 0.44-0.95) for aortic...

Increased half-life and enhanced potency of Fc-modified human PCSK9 monoclonal antibodies in primates.

Directory of Open Access Journals (Sweden)

Yijun Shen

Full Text Available Blocking proprotein convertase subtilisin kexin type 9 (PCSK9 binding to low-density lipoprotein receptor (LDLR can profoundly lower plasma LDL levels. Two anti-PCKS9 monoclonal antibodies (mAbs, alirocumab and evolocumab, were approved by the FDA in 2015. The recommended dose is 75 mg to 150 mg every two weeks for alirocumab and 140mg every two weeks or 420 mg once a month for evolocumab. This study attempted to improve the pharmacokinetic properties of F0016A, an IgG1 anti-PCKS9 mAb, to generate biologically superior molecules. We engineered several variants with two or three amino acid substitutions in the Fc fragment based on prior knowledge. The Fc-modified mAbs exhibited increased binding to FcRn, resulting in prolonged serum half-life and enhanced efficacy in vivo. These results demonstrate that Fc-modified anti-PCKS9 antibodies may enable less frequent or lower dosing of antibodies by improved recycling into the blood.

An encoding device and a method of encoding

DEFF Research Database (Denmark)

2012-01-01

The present invention relates to an encoding device, such as an optical position encoder, for encoding input from an object, and a method for encoding input from an object, for determining a position of an object that interferes with light of the device. The encoding device comprises a light source...... in the area in the space and may interfere with the light, which interference may be encoded into a position or activation....

Hepatic S1P deficiency lowers plasma cholesterol levels in apoB-containing lipoproteins when LDLR function is compromised.

Science.gov (United States)

Basu, Debapriya; Huq, Afroza; Iqbal, Jahangir; Hussain, M Mahmood; Jiang, Xian-Cheng; Jin, Weijun

2015-01-01

Site-1 protease (S1P) is the key enzyme required for activation of the sterol regulatory element binding proteins (SREBPs) that govern lipid synthesis. While S1P has been speculated to influence plasma apoB-containing lipoprotein (Blp) metabolism, there has been little investigative work. LDL receptor (LDLR) is the major receptor for clearing plasma LDL cholesterol (LDL-c). Proprotein convertase subtilisin kexin type 9 (PCSK9) modulates LDL-c through post-translational degradation of the LDLR. A hepatic-specific knockdown (KD) of S1P was achieved using floxed S1P mouse models (S1P(f/f) and LDLR(-/-)S1P(f/f)) and hepatic expression of Cre recombinase. Lipids were measured in total plasma and size fractionated plasma using colorimetric assays. Realtime polymerase chain reaction, western blotting and ELISA were used to determine hepatic expression of key genes/protein. Plasmid mediated overexpression and siRNA mediated knockdown of genes were performed in mouse primary hepatocytes to determine the mechanistic basis of PCSK9 gene regulation. A hepatic-specific KD of S1P resulted in a 45 % and 38 % reduction in plasma total cholesterol and triglyceride levels, respectively. Hepatic S1P KD had a minimal effect on plasma Blp cholesterol (Blp-c) in S1P(f/f) mice, despite significantly reducing VLDL secretion. Notably, hepatic S1P KD decreased the LDL receptor (LDLR) mRNA expression by 50 %. However, the reduction in LDLR protein levels was less than that of mRNA expression, especially under fed conditions. Further assessment of hepatic S1P deficiency revealed that it increased LDLR protein stability in vivo. Mechanistically, hepatic S1P KD was shown to decrease the liver and plasma levels of the protein proprotein convertase subtilisin/kexin type 9 (PCSK9), which degrades LDLR protein. This effect was more prominent in the fed condition and sufficient to account for the discordance in LDLR mRNA and protein levels. Furthermore, hepatic S1P was shown to regulate PCSK9

Processing of high-molecular-weight form adrenocorticotropin in human adrenocorticotropin-secreting tumor cell line (DMS-79) after transfection of prohormone convertase 1/3 gene.

Science.gov (United States)

Tateno, T; Kato, M; Tani, Y; Yoshimoto, T; Oki, Y; Hirata, Y

2010-02-01

Ectopic ACTH-producing tumors preferentially secrete biologically inactive ACTH precursors and ACTH-related fragments. DMS-79 is known to secrete unprocessed high-molecular-weight (HMW) form ACTH. To determine whether prohormone convertase (PC) 1/3 is involved in the abnormal processing of proopiomelanocortin (POMC), we studied whether PC1/3 and 2 genes are expressed in DMS-79, and whether overexpression of PC1/3 gene affects POMC processing pattern. Steady-state mRNA levels of PC1/3 and 2 were determined by real-time RT-PCR. Molecular weights of ACTH-related peptides were determined by chromatographical analyses coupled with ACTH and beta-endorphin (beta-END) radioimmunoassays. PC1/3 gene was transfected into DMS-79 by retrovirus transduction using pMX-IP vector encoding PC1/3 cDNA. The steady-state mRNA levels of PC1/3 and 2 in DMS-79 were lower than those in ACTH-secreting and nonfunctioning pituitary tumors. DMS-79 predominantly secreted HMW form with both ACTH and beta-END immunoreactivities by size-exclusion chromatography. After purification by immunoaffinity chromatography with anti-ACTH antibody, the apparent molecular weight of HMW form ACTH was estimated to be 16 kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis with silver staining. After retroviral transfection of PC1/3 cDNA into DMS-79 and puromycin selection, PC1/3 stably-expressing cell line (DMS-79T) secreted two immunoreactive ACTH components, a major one coeluting with ACTH(1-39) and a minor one as a HMW form as well as two beta- END immunoreactive components coeluting with beta-lipotropic hormone and beta-END, respectively. Thus, we have established PC1/3 stably-expressing cell line (DMS-79T) capable of proteolytically processing ACTH precursor molecule(s) into mature ACTH and beta-END.

Regulation of PCSK9 by nutraceuticals.

Science.gov (United States)

Momtazi, Amir Abbas; Banach, Maciej; Pirro, Matteo; Katsiki, Niki; Sahebkar, Amirhossein

2017-06-01

PCSK9 (proprotein convertase subtilisin kexin type 9) is a liver secretory enzyme that regulates plasma low-density lipoprotein (LDL) cholesterol (LDL-C) levels through modulation of LDL receptor (LDLR) density on the surface of hepatocytes. Inhibition of PCSK9 using monoclonal antibodies can efficiently lower plasma LDL-C, non-high-density lipoprotein cholesterol and lipoprotein (a). PCSK9 inhibition is also an effective adjunct to statin therapy; however, the cost-effectiveness of currently available PCSK9 inhibitors is under question. Nutraceuticals offer a safe and cost-effective option for PCSK9 inhibition. Several nutraceuticals have been reported to modulate PCSK9 levels and exert LDL-lowering activity. Mechanistically, those nutraceuticals that inhibit PCSK9 through a SREBP (sterol-responsive element binding protein)-independent pathway can be more effective in lowering plasma LDL-C levels compared with those inhibiting PCSK9 through the SREBP pathway. The present review aims to collect available data on the nutraceuticals with PCSK9-inhibitory effect and the underlying mechanisms. Copyright © 2017 Elsevier Ltd. All rights reserved.

Antibodies to watch in 2014.

Science.gov (United States)

Reichert, Janice M

2014-01-01

Since 2010, mAbs has documented the biopharmaceutical industry's progress in transitioning antibody therapeutics to first Phase 3 clinical studies and regulatory review, and its success at gaining first marketing approvals for antibody-based products. This installment of the "Antibodies to watch" series outlines events anticipated to occur between December 2013 and the end of 2014, including first regulatory actions on marketing applications for vedolizumab, siltuximab, and ramucirumab, as well as the Fc fusion proteins Factor IX-Fc and Factor VIII-Fc; and the submission of first marketing applications for up to five therapeutics (secukinumab, ch14.18, onartuzumab, necitumumab, gevokizumab). Antibody therapeutics in Phase 3 studies are described, with an emphasis on those with study completion dates in 2014, including antibodies targeting interleukin-17a or the interleukin-17a receptor (secukinumab, ixekizumab, brodalumab), proprotein convertase subtilisin/kexin type 9 (alirocumab, evolocumab, bococizumab), and programmed death 1 receptor (lambrolizumab, nivolumab). Five antibodies with US Food and Drug Administration's Breakthrough Therapy designation (obinutuzumab, ofatumumab, lambrolizumab, bimagrumab, daratumumab) are also discussed.

Compartment-Specific Biosensors Reveal a Complementary Subcellular Distribution of Bioactive Furin and PC7

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Pierpaolo Ginefra

2018-02-01

Full Text Available Furin trafficking, and that of related proprotein convertases (PCs, may regulate which substrates are accessible for endoproteolysis, but tools to directly test this hypothesis have been lacking. Here, we develop targeted biosensors that indicate Furin activity in endosomes is 10-fold less inhibited by decanoyl-RVKR-chloromethylketone and enriched >3-fold in endosomes compared to the trans-Golgi network (TGN. Endogenous PC7, which resists this inhibitor, was active in distinct vesicles. Only overexpressed PC7 activity reached the cell surface, endosomes, and the TGN. A PLC motif in the cytosolic tail of PC7 was dispensable for endosomal activity, but it was specifically required for TGN recycling and to rescue proActivin-A cleavage in Furin-depleted B16F1 melanoma cells. In sharp contrast, PC7 complemented Furin in cleaving Notch1 independently of PLC-mediated TGN access. Our study provides a proof in principle that compartment-specific biosensors can be used to gain insight into the regulation of PC trafficking and to map the tropism of PC-specific inhibitors.

Recent advances in preventing stroke recurrence [version 1; referees: 2 approved

Directory of Open Access Journals (Sweden)

J David Spence

2017-06-01

Full Text Available Recent advances in secondary stroke prevention include new evidence in hypertension, nutrition, anticoagulation, antiplatelet therapy, intracranial stenosis, percutaneous closure of patent foramen ovale, and lipid-lowering therapy. Individualized therapy for hypertension based on phenotyping with plasma renin and aldosterone markedly improves blood pressure control in patients with resistant hypertension. A Mediterranean diet can reduce the risk of stroke by nearly half. The diagnosis and treatment of metabolic vitamin B12 deficiency, and B vitamins to lower homocysteine, can reduce the risk of stroke by approximately 30%. There are problems with clopidogrel that can be overcome by using ticagrelor, and new anticoagulant drugs markedly improve anticoagulation for stroke prevention, particularly in atrial fibrillation. There are pharmacokinetic problems with dabigatran that deserve attention. Intensive medical therapy is better than stenting for intracranial stenosis, and new therapies directed at proprotein convertase subtilisin–kexin type 9 (PCSK9 will revolutionize lipid-lowering therapy. In the past, it was estimated that rational therapy could reduce recurrent stroke by about 80%. With recent advances, we should be able to do even better.

Evolution of sequence-defined highly functionalized nucleic acid polymers

Science.gov (United States)

Chen, Zhen; Lichtor, Phillip A.; Berliner, Adrian P.; Chen, Jonathan C.; Liu, David R.

2018-03-01

The evolution of sequence-defined synthetic polymers made of building blocks beyond those compatible with polymerase enzymes or the ribosome has the potential to generate new classes of receptors, catalysts and materials. Here we describe a ligase-mediated DNA-templated polymerization and in vitro selection system to evolve highly functionalized nucleic acid polymers (HFNAPs) made from 32 building blocks that contain eight chemically diverse side chains on a DNA backbone. Through iterated cycles of polymer translation, selection and reverse translation, we discovered HFNAPs that bind proprotein convertase subtilisin/kexin type 9 (PCSK9) and interleukin-6, two protein targets implicated in human diseases. Mutation and reselection of an active PCSK9-binding polymer yielded evolved polymers with high affinity (KD = 3 nM). This evolved polymer potently inhibited the binding between PCSK9 and the low-density lipoprotein receptor. Structure-activity relationship studies revealed that specific side chains at defined positions in the polymers are required for binding to their respective targets. Our findings expand the chemical space of evolvable polymers to include densely functionalized nucleic acids with diverse, researcher-defined chemical repertoires.

The role of proteolytic processing and the stable signal peptide in expression of the Old World arenavirus envelope glycoprotein ectodomain

International Nuclear Information System (INIS)

Burri, Dominique J.; Pasquato, Antonella; Ramos da Palma, Joel; Igonet, Sebastien; Oldstone, Michael B.A.; Kunz, Stefan

2013-01-01

Maturation of the arenavirus GP precursor (GPC) involves proteolytic processing by cellular signal peptidase and the proprotein convertase subtilisin kexin isozyme 1 (SKI-1)/site 1 protease (S1P), yielding a tripartite complex comprised of a stable signal peptide (SSP), the receptor-binding GP1, and the fusion-active transmembrane GP2. Here we investigated the roles of SKI-1/S1P processing and SSP in the biosynthesis of the recombinant GP ectodomains of lymphocytic choriomeningitis virus (LCMV) and Lassa virus (LASV). When expressed in mammalian cells, the LCMV and LASV GP ectodomains underwent processing by SKI-1/S1P, followed by dissociation of GP1 from GP2. The GP2 ectodomain spontaneously formed trimers as revealed by chemical cross-linking. The endogenous SSP, known to be crucial for maturation and transport of full-length arenavirus GPC was dispensable for processing and secretion of the soluble GP ectodomain, suggesting a specific role of SSP in the stable prefusion conformation and transport of full-length GPC.

The role of proteolytic processing and the stable signal peptide in expression of the Old World arenavirus envelope glycoprotein ectodomain

Energy Technology Data Exchange (ETDEWEB)

Burri, Dominique J.; Pasquato, Antonella; Ramos da Palma, Joel [Institute of Microbiology, University Hospital Center and University of Lausanne, Lausanne CH-1011 (Switzerland); Igonet, Sebastien; Oldstone, Michael B.A. [Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037 (United States); Kunz, Stefan, E-mail: Stefan.Kunz@chuv.ch [Institute of Microbiology, University Hospital Center and University of Lausanne, Lausanne CH-1011 (Switzerland)

2013-02-05

Maturation of the arenavirus GP precursor (GPC) involves proteolytic processing by cellular signal peptidase and the proprotein convertase subtilisin kexin isozyme 1 (SKI-1)/site 1 protease (S1P), yielding a tripartite complex comprised of a stable signal peptide (SSP), the receptor-binding GP1, and the fusion-active transmembrane GP2. Here we investigated the roles of SKI-1/S1P processing and SSP in the biosynthesis of the recombinant GP ectodomains of lymphocytic choriomeningitis virus (LCMV) and Lassa virus (LASV). When expressed in mammalian cells, the LCMV and LASV GP ectodomains underwent processing by SKI-1/S1P, followed by dissociation of GP1 from GP2. The GP2 ectodomain spontaneously formed trimers as revealed by chemical cross-linking. The endogenous SSP, known to be crucial for maturation and transport of full-length arenavirus GPC was dispensable for processing and secretion of the soluble GP ectodomain, suggesting a specific role of SSP in the stable prefusion conformation and transport of full-length GPC.

The Potential Mechanisms of Berberine in the Treatment of Nonalcoholic Fatty Liver Disease

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Xiaopeng Zhu

2016-10-01

Full Text Available Nonalcoholic fatty liver disease (NAFLD is a globally observed metabolic disease with high prevalence both in adults and children. However, there is no efficient medication available yet. Increased evidence indicates that berberine (BBR, a natural plant product, has beneficial effects on NAFLD, though the mechanisms are not completely known. In this review, we briefly summarize the pathogenesis of NAFLD and factors that influence the progression of NAFLD, and focus on the potential mechanisms of BBR in the treatment of NAFLD. Increase of insulin sensitivity, regulation of adenosine monophosphate-activated protein kinase (AMPK pathway, improvement of mitochondrial function, alleviation of oxidative stress, LDLR mRNA stabilization, and regulation of gut microenvironment are the major targets of BBR in the treatment of NAFLD. Additionally, reduction of proprotein convertase subtilisin/kexin 9 (PCSK9 expression and DNA methylation are also involved in pharmacological mechanisms of berberine in the treatment of NAFLD. The immunologic mechanism of BBR in the treatment of NAFLD, development of berberine derivative, drug combinations, delivery routes, and drug dose can be considered in the future research.

SnoVault and encodeD: A novel object-based storage system and applications to ENCODE metadata.

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Benjamin C Hitz

Full Text Available The Encyclopedia of DNA elements (ENCODE project is an ongoing collaborative effort to create a comprehensive catalog of functional elements initiated shortly after the completion of the Human Genome Project. The current database exceeds 6500 experiments across more than 450 cell lines and tissues using a wide array of experimental techniques to study the chromatin structure, regulatory and transcriptional landscape of the H. sapiens and M. musculus genomes. All ENCODE experimental data, metadata, and associated computational analyses are submitted to the ENCODE Data Coordination Center (DCC for validation, tracking, storage, unified processing, and distribution to community resources and the scientific community. As the volume of data increases, the identification and organization of experimental details becomes increasingly intricate and demands careful curation. The ENCODE DCC has created a general purpose software system, known as SnoVault, that supports metadata and file submission, a database used for metadata storage, web pages for displaying the metadata and a robust API for querying the metadata. The software is fully open-source, code and installation instructions can be found at: http://github.com/ENCODE-DCC/snovault/ (for the generic database and http://github.com/ENCODE-DCC/encoded/ to store genomic data in the manner of ENCODE. The core database engine, SnoVault (which is completely independent of ENCODE, genomic data, or bioinformatic data has been released as a separate Python package.

Peptide IC-20, encoded by skin kininogen-1 of the European yellow-bellied toad, Bombina variegata, antagonizes bradykinin-induced arterial smooth muscle relaxation

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Mu Yang

2011-01-01

Full Text Available Objectives: The objectives were to determine if the skin secretion of the European yellow-bellied toad (Bombina variegata, in common with other related species, contains a bradykinin inhibitor peptide and to isolate and structurally characterize this peptide. Materials and Methods: Lyophilized skin secretion obtained from this toad was subjected to reverse phase HPLC fractionation with subsequent bioassay of fractions for antagonism of the bradykinin activity using an isolated rat tail artery smooth muscle preparation. Subsequently, the primary structure of the peptide was established by a combination of microsequencing, mass spectroscopy, and molecular cloning, following which a synthetic replicate was chemically synthesised for bioassay. Results: A single peptide of molecular mass 2300.92 Da was resolved in HPLC fractions of skin secretion and its primary structure determined as IYNAIWP-KH-NK-KPGLL-. Database interrogation with this sequence indicated that this peptide was encoded by skin kininogen-1 previously cloned from B. variegata. The blank cycles were occupied by cysteinyl (C residues and the peptide was located toward the C-terminus of the skin kininogen, and flanked N-terminally by a classical -KR- propeptide convertase processing site. The peptide was named IC-20 in accordance (I = N-terminal isoleucine, C = C-terminal cysteine, 20 = number of residues. Like the natural peptide, its synthetic replicate displayed an antagonism of bradykinin-induced arterial smooth muscle relaxation. Conclusion: IC-20 represents a novel bradykinin antagonizing peptide from amphibian skin secretions and is the third such peptide found to be co-encoded with bradykinins within skin kininogens.

Transcriptomic Analysis of Neuropeptides and Peptide Hormones in the Barnacle Balanus amphitrite: Evidence of Roles in Larval Settlement

Science.gov (United States)

Yan, Xing-Cheng; Chen, Zhang-Fan; Sun, Jin; Matsumura, Kiyotaka; Wu, Rudolf S. S.; Qian, Pei-Yuan

2012-01-01

The barnacle Balanus amphitrite is a globally distributed marine crustacean and has been used as a model species for intertidal ecology and biofouling studies. Its life cycle consists of seven planktonic larval stages followed by a sessile juvenile/adult stage. The transitional processes between larval stages and juveniles are crucial for barnacle development and recruitment. Although some studies have been conducted on the neuroanatomy and neuroactive substances of the barnacle, a comprehensive understanding of neuropeptides and peptide hormones remains lacking. To better characterize barnacle neuropeptidome and its potential roles in larval settlement, an in silico identification of putative transcripts encoding neuropeptides/peptide hormones was performed, based on transcriptome of the barnacle B. amphitrite that has been recently sequenced. Potential cleavage sites andstructure of mature peptides were predicted through homology search of known arthropod peptides. In total, 16 neuropeptide families/subfamilies were predicted from the barnacle transcriptome, and 14 of them were confirmed as genuine neuropeptides by Rapid Amplification of cDNA Ends. Analysis of peptide precursor structures and mature sequences showed that some neuropeptides of B. amphitrite are novel isoforms and shared similar characteristics with their homologs from insects. The expression profiling of predicted neuropeptide genes revealed that pigment dispersing hormone, SIFamide, calcitonin, and B-type allatostatin had the highest expression level in cypris stage, while tachykinin-related peptide was down regulated in both cyprids and juveniles. Furthermore, an inhibitor of proprotein convertase related to peptide maturation effectively delayed larval metamorphosis. Combination of real-time PCR results and bioassay indicated that certain neuropeptides may play an important role in cypris settlement. Overall, new insight into neuropeptides/peptide hormones characterized in this study shall

Transcriptomic analysis of neuropeptides and peptide hormones in the barnacle Balanus amphitrite: evidence of roles in larval settlement.

KAUST Repository

Yan, Xing-Cheng

2012-10-02

The barnacle Balanus amphitrite is a globally distributed marine crustacean and has been used as a model species for intertidal ecology and biofouling studies. Its life cycle consists of seven planktonic larval stages followed by a sessile juvenile/adult stage. The transitional processes between larval stages and juveniles are crucial for barnacle development and recruitment. Although some studies have been conducted on the neuroanatomy and neuroactive substances of the barnacle, a comprehensive understanding of neuropeptides and peptide hormones remains lacking. To better characterize barnacle neuropeptidome and its potential roles in larval settlement, an in silico identification of putative transcripts encoding neuropeptides/peptide hormones was performed, based on transcriptome of the barnacle B. amphitrite that has been recently sequenced. Potential cleavage sites andstructure of mature peptides were predicted through homology search of known arthropod peptides. In total, 16 neuropeptide families/subfamilies were predicted from the barnacle transcriptome, and 14 of them were confirmed as genuine neuropeptides by Rapid Amplification of cDNA Ends. Analysis of peptide precursor structures and mature sequences showed that some neuropeptides of B. amphitrite are novel isoforms and shared similar characteristics with their homologs from insects. The expression profiling of predicted neuropeptide genes revealed that pigment dispersing hormone, SIFamide, calcitonin, and B-type allatostatin had the highest expression level in cypris stage, while tachykinin-related peptide was down regulated in both cyprids and juveniles. Furthermore, an inhibitor of proprotein convertase related to peptide maturation effectively delayed larval metamorphosis. Combination of real-time PCR results and bioassay indicated that certain neuropeptides may play an important role in cypris settlement. Overall, new insight into neuropeptides/peptide hormones characterized in this study shall

Transcriptomic analysis of neuropeptides and peptide hormones in the barnacle Balanus amphitrite: evidence of roles in larval settlement.

Directory of Open Access Journals (Sweden)

Xing-Cheng Yan

Full Text Available The barnacle Balanus amphitrite is a globally distributed marine crustacean and has been used as a model species for intertidal ecology and biofouling studies. Its life cycle consists of seven planktonic larval stages followed by a sessile juvenile/adult stage. The transitional processes between larval stages and juveniles are crucial for barnacle development and recruitment. Although some studies have been conducted on the neuroanatomy and neuroactive substances of the barnacle, a comprehensive understanding of neuropeptides and peptide hormones remains lacking. To better characterize barnacle neuropeptidome and its potential roles in larval settlement, an in silico identification of putative transcripts encoding neuropeptides/peptide hormones was performed, based on transcriptome of the barnacle B. amphitrite that has been recently sequenced. Potential cleavage sites andstructure of mature peptides were predicted through homology search of known arthropod peptides. In total, 16 neuropeptide families/subfamilies were predicted from the barnacle transcriptome, and 14 of them were confirmed as genuine neuropeptides by Rapid Amplification of cDNA Ends. Analysis of peptide precursor structures and mature sequences showed that some neuropeptides of B. amphitrite are novel isoforms and shared similar characteristics with their homologs from insects. The expression profiling of predicted neuropeptide genes revealed that pigment dispersing hormone, SIFamide, calcitonin, and B-type allatostatin had the highest expression level in cypris stage, while tachykinin-related peptide was down regulated in both cyprids and juveniles. Furthermore, an inhibitor of proprotein convertase related to peptide maturation effectively delayed larval metamorphosis. Combination of real-time PCR results and bioassay indicated that certain neuropeptides may play an important role in cypris settlement. Overall, new insight into neuropeptides/peptide hormones characterized in

Transcriptomic analysis of neuropeptides and peptide hormones in the barnacle Balanus amphitrite: evidence of roles in larval settlement.

KAUST Repository

Yan, Xing-Cheng; Chen, Zhang-Fan; Sun, Jin; Matsumura, Kiyotaka; Wu, Rudolf S S; Qian, Pei-Yuan

2012-01-01

The barnacle Balanus amphitrite is a globally distributed marine crustacean and has been used as a model species for intertidal ecology and biofouling studies. Its life cycle consists of seven planktonic larval stages followed by a sessile juvenile/adult stage. The transitional processes between larval stages and juveniles are crucial for barnacle development and recruitment. Although some studies have been conducted on the neuroanatomy and neuroactive substances of the barnacle, a comprehensive understanding of neuropeptides and peptide hormones remains lacking. To better characterize barnacle neuropeptidome and its potential roles in larval settlement, an in silico identification of putative transcripts encoding neuropeptides/peptide hormones was performed, based on transcriptome of the barnacle B. amphitrite that has been recently sequenced. Potential cleavage sites andstructure of mature peptides were predicted through homology search of known arthropod peptides. In total, 16 neuropeptide families/subfamilies were predicted from the barnacle transcriptome, and 14 of them were confirmed as genuine neuropeptides by Rapid Amplification of cDNA Ends. Analysis of peptide precursor structures and mature sequences showed that some neuropeptides of B. amphitrite are novel isoforms and shared similar characteristics with their homologs from insects. The expression profiling of predicted neuropeptide genes revealed that pigment dispersing hormone, SIFamide, calcitonin, and B-type allatostatin had the highest expression level in cypris stage, while tachykinin-related peptide was down regulated in both cyprids and juveniles. Furthermore, an inhibitor of proprotein convertase related to peptide maturation effectively delayed larval metamorphosis. Combination of real-time PCR results and bioassay indicated that certain neuropeptides may play an important role in cypris settlement. Overall, new insight into neuropeptides/peptide hormones characterized in this study shall

Opposite Roles of Furin and PC5A in N-Cadherin Processing

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Deborah Maret

2012-10-01

Full Text Available We recently demonstrated that lack of Furin-processing of the N-cadherin precursor (proNCAD in highly invasive melanoma and brain tumor cells results in the cell-surface expression of a nonadhesive protein favoring cell migration and invasion in vitro. Quantitative polymerase chain reaction analysis of malignant human brain tumor cells revealed that of all proprotein convertases (PCs only the levels of Furin and PC5A are modulated, being inversely (Furin or directly (PC5A correlated with brain tumor invasive capacity. Intriguingly, the N-terminal sequence following the Furin-activated NCAD site (RQKR↓DW161, mouse nomenclature reveals a second putative PC-processing site (RIRSDR↓DK189 located in the first extracellular domain. Cleavage at this site would abolish the adhesive functions of NCAD because of the loss of the critical Trp161. This was confirmed upon analysis of the fate of the endogenous prosegment of proNCAD in human malignant glioma cells expressing high levels of Furin and low levels of PC5A (U343 or high levels of PC5A and negligible Furin levels (U251. Cellular analyses revealed that Furin is the best activating convertase releasing an ∼17-kDa prosegment, whereas PC5A is the major inactivating enzyme resulting in the secretion of an ∼20-kDa product. Like expression of proNCAD at the cell surface, cleavage of the NCAD molecule at RIRSDR↓DK189 renders the U251 cancer cells less adhesive to one another and more migratory. Our work modifies the present view on posttranslational processing and surface expression of classic cadherins and clarifies how NCAD possesses a range of adhesive potentials and plays a critical role in tumor progression.

ERP Correlates of Encoding Success and Encoding Selectivity in Attention Switching

Science.gov (United States)

Yeung, Nick

2016-01-01

Long-term memory encoding depends critically on effective processing of incoming information. The degree to which participants engage in effective encoding can be indexed in electroencephalographic (EEG) data by studying event-related potential (ERP) subsequent memory effects. The current study investigated ERP correlates of memory success operationalised with two different measures—memory selectivity and global memory—to assess whether previously observed ERP subsequent memory effects reflect focused encoding of task-relevant information (memory selectivity), general encoding success (global memory), or both. Building on previous work, the present study combined an attention switching paradigm—in which participants were presented with compound object-word stimuli and switched between attending to the object or the word across trials—with a later recognition memory test for those stimuli, while recording their EEG. Our results provided clear evidence that subsequent memory effects resulted from selective attentional focusing and effective top-down control (memory selectivity) in contrast to more general encoding success effects (global memory). Further analyses addressed the question of whether successful encoding depended on similar control mechanisms to those involved in attention switching. Interestingly, differences in the ERP correlates of attention switching and successful encoding, particularly during the poststimulus period, indicated that variability in encoding success occurred independently of prestimulus demands for top-down cognitive control. These results suggest that while effects of selective attention and selective encoding co-occur behaviourally their ERP correlates are at least partly dissociable. PMID:27907075

Rational redesign of inhibitors of furin/kexin processing proteases by electrostatic mutations.

Science.gov (United States)

Cai, Xiao-hui; Zhang, Qing; Ding, Da-fu

2004-12-01

To model the three-dimensional structure and investigate the interaction mechanism of the proprotein convertase furin/kexin and their inhibitors (eglin c mutants). The three-dimensional complex structures of furin/kexin with its inhibitors, eglin c mutants, were generated by modeller program using the newly published X-ray crystallographical structures of mouse furin and yeast kexin as templates. The electrostatic interaction energy of each complex was calculated and the results were compared with the experimentally determined inhibition constants to find the correlation between them. High quality models of furin/kexin-eglin c mutants were obtained and used for calculation of the electrostatic interaction energies between the proteases and their inhibitors. The calculated electrostatic energies of interaction showed a linear correlation to the experimental inhibition constants. The modeled structures give good explanations of the specificity of eglin c mutants to furin/kexin. The electrostatic interactions play important roles in inhibitory activity of eglin c mutants to furin/kexin. The results presented here provided quantitative structural and functional information concerning the role of the charge-charge interactions in the binding of furin/kexin and their inhibitors.

Enhancement in production of recombinant two-chain Insulin Glargine by over-expression of Kex2 protease in Pichia pastoris.

Science.gov (United States)

Sreenivas, Suma; Krishnaiah, Sateesh M; Govindappa, Nagaraja; Basavaraju, Yogesh; Kanojia, Komal; Mallikarjun, Niveditha; Natarajan, Jayaprakash; Chatterjee, Amarnath; Sastry, Kedarnath N

2015-01-01

Glargine is an analog of Insulin currently being produced by recombinant DNA technology using two different hosts namely Escherichia coli and Pichia pastoris. Production from E. coli involves the steps of extraction of inclusion bodies by cell lysis, refolding, proteolytic cleavage and purification. In P. pastoris, a single-chain precursor with appropriate disulfide bonding is secreted to the medium. Downstream processing currently involves use of trypsin which converts the precursor into two-chain final product. The use of trypsin in the process generates additional impurities due to presence of Lys and Arg residues in the Glargine molecule. In this study, we describe an alternate approach involving over-expression of endogenous Kex2 proprotein convertase, taking advantage of dibasic amino acid sequence (Arg-Arg) at the end of B-chain of Glargine. KEX2 gene over-expression in Pichia was accomplished by using promoters of varying strengths to ensure production of greater levels of fully functional two-chain Glargine product, confirmed by HPLC and mass analysis. In conclusion, this new production process involving Kex2 protease over-expression improves the downstream process efficiency, reduces the levels of impurities generated and decreases the use of raw materials.

[New agents for hypercholesterolemia].

Science.gov (United States)

Pintó, Xavier; García Gómez, María Carmen

2016-02-19

An elevated proportion of high cardiovascular risk patients do not achieve the therapeutic c-LDL goals. This owes to physicians' inappropriate or insufficient use of cholesterol lowering medications or to patients' bad tolerance or therapeutic compliance. Another cause is an insufficient efficacy of current cholesterol lowering drugs including statins and ezetimibe. In addition, proprotein convertase subtilisin kexin type 9 inhibitors are a new cholesterol lowering medications showing safety and high efficacy to reduce c-LDL in numerous already performed or underway clinical trials, potentially allowing an optimal control of hypercholesterolemia in most patients. Agents inhibiting apolipoprotein B synthesis and microsomal transfer protein are also providing a new potential to decrease cholesterol in patients with severe hypercholesterolemia and in particular in homozygote familial hypercholesterolemia. Last, cholesteryl ester transfer protein inhibitors have shown powerful effects on c-HDL and c-LDL, although their efficacy in cardiovascular prevention and safety has not been demonstrated yet. We provide in this article an overview of the main characteristics of therapeutic agents for hypercholesterolemia, which have been recently approved or in an advanced research stage. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

Thyroid hormone reduces PCSK9 and stimulates bile acid synthesis in humans[S

Science.gov (United States)

Bonde, Ylva; Breuer, Olof; Lütjohann, Dieter; Sjöberg, Stefan; Angelin, Bo; Rudling, Mats

2014-01-01

Reduced plasma LDL-cholesterol is a hallmark of hyperthyroidism and is caused by transcriptional stimulation of LDL receptors in the liver. Here, we investigated whether thyroid hormone (TH) actions involve other mechanisms that may also account for the reduction in LDL-cholesterol, including effects on proprotein convertase subtilisin/kexin type 9 (PCSK9) and bile acid synthesis. Twenty hyperthyroid patients were studied before and after clinical normalization, and the responses to hyperthyroidism were compared with those in 14 healthy individuals after 14 days of treatment with the liver-selective TH analog eprotirome. Both hyperthyroidism and eprotirome treatment reduced circulating PCSK9, lipoprotein cholesterol, apoB and AI, and lipoprotein(a), while cholesterol synthesis was stable. Hyperthyroidism, but not eprotirome treatment, markedly increased bile acid synthesis and reduced fibroblast growth factor (FGF) 19 and dietary cholesterol absorption. Eprotirome treatment, but not hyperthyroidism, reduced plasma triglycerides. Neither hyperthyroidism nor eprotirome treatment altered insulin, glucose, or FGF21 levels. TH reduces circulating PSCK9, thereby likely contributing to lower plasma LDL-cholesterol in hyperthyroidism. TH also stimulates bile acid synthesis, although this response is not critical for its LDL-lowering effect. PMID:25172631

Displacement encoder

International Nuclear Information System (INIS)

Hesketh, T.G.

1983-01-01

In an optical encoder, light from an optical fibre input A is encoded by means of the encoding disc and is subsequently collected for transmission via optical fibre B. At some point in the optical path between the fibres A and B, the light is separated into component form by means of a filtering or dispersive system and each colour component is associated with a respective one of the coding channels of the disc. In this way, the significance of each bit of the coded information is represented by a respective colour thereby enabling the components to be re-combined for transmission by the fibre B without loss of information. (author)

Cloud-based uniform ChIP-Seq processing tools for modENCODE and ENCODE.

Science.gov (United States)

Trinh, Quang M; Jen, Fei-Yang Arthur; Zhou, Ziru; Chu, Kar Ming; Perry, Marc D; Kephart, Ellen T; Contrino, Sergio; Ruzanov, Peter; Stein, Lincoln D

2013-07-22

Funded by the National Institutes of Health (NIH), the aim of the Model Organism ENCyclopedia of DNA Elements (modENCODE) project is to provide the biological research community with a comprehensive encyclopedia of functional genomic elements for both model organisms C. elegans (worm) and D. melanogaster (fly). With a total size of just under 10 terabytes of data collected and released to the public, one of the challenges faced by researchers is to extract biologically meaningful knowledge from this large data set. While the basic quality control, pre-processing, and analysis of the data has already been performed by members of the modENCODE consortium, many researchers will wish to reinterpret the data set using modifications and enhancements of the original protocols, or combine modENCODE data with other data sets. Unfortunately this can be a time consuming and logistically challenging proposition. In recognition of this challenge, the modENCODE DCC has released uniform computing resources for analyzing modENCODE data on Galaxy (https://github.com/modENCODE-DCC/Galaxy), on the public Amazon Cloud (http://aws.amazon.com), and on the private Bionimbus Cloud for genomic research (http://www.bionimbus.org). In particular, we have released Galaxy workflows for interpreting ChIP-seq data which use the same quality control (QC) and peak calling standards adopted by the modENCODE and ENCODE communities. For convenience of use, we have created Amazon and Bionimbus Cloud machine images containing Galaxy along with all the modENCODE data, software and other dependencies. Using these resources provides a framework for running consistent and reproducible analyses on modENCODE data, ultimately allowing researchers to use more of their time using modENCODE data, and less time moving it around.

Flipped-Adversarial AutoEncoders

OpenAIRE

Zhang, Jiyi; Dang, Hung; Lee, Hwee Kuan; Chang, Ee-Chien

2018-01-01

We propose a flipped-Adversarial AutoEncoder (FAAE) that simultaneously trains a generative model G that maps an arbitrary latent code distribution to a data distribution and an encoder E that embodies an "inverse mapping" that encodes a data sample into a latent code vector. Unlike previous hybrid approaches that leverage adversarial training criterion in constructing autoencoders, FAAE minimizes re-encoding errors in the latent space and exploits adversarial criterion in the data space. Exp...

a permutation encoding te algorithm solution of reso tation encoding

African Journals Online (AJOL)

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Keywords: Genetic algorithm, resource constrained. 1. INTRODUCTION. 1. .... Nigerian Journal of Technology. Vol. 34, No. 1, January 2015. 128 ... 4. ENCODING OF CHROMOSOME. ENCODING OF CHROMOSOME .... International Multi conference of Engineers and ... method”, Naval Research Logistics, vol 48, issue 2,.

Selecting Operations for Assembler Encoding

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Tomasz Praczyk

2010-04-01

Full Text Available Assembler Encoding is a neuro-evolutionary method in which a neural network is represented in the form of a simple program called Assembler Encoding Program. The task of the program is to create the so-called Network Definition Matrix which maintains all the information necessary to construct the network. To generate Assembler Encoding Programs and the subsequent neural networks evolutionary techniques are used.
The performance of Assembler Encoding strongly depends on operations used in Assembler Encoding Programs. To select the most effective operations, experiments in the optimization and the predator-prey problem were carried out. In the experiments, Assembler Encoding Programs equipped with different types of operations were tested. The results of the tests are presented at the end of the paper.

Bioinformatics-Aided Venomics

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Quentin Kaas

2015-06-01

Full Text Available Venomics is a modern approach that combines transcriptomics and proteomics to explore the toxin content of venoms. This review will give an overview of computational approaches that have been created to classify and consolidate venomics data, as well as algorithms that have helped discovery and analysis of toxin nucleic acid and protein sequences, toxin three-dimensional structures and toxin functions. Bioinformatics is used to tackle specific challenges associated with the identification and annotations of toxins. Recognizing toxin transcript sequences among second generation sequencing data cannot rely only on basic sequence similarity because toxins are highly divergent. Mass spectrometry sequencing of mature toxins is challenging because toxins can display a large number of post-translational modifications. Identifying the mature toxin region in toxin precursor sequences requires the prediction of the cleavage sites of proprotein convertases, most of which are unknown or not well characterized. Tracing the evolutionary relationships between toxins should consider specific mechanisms of rapid evolution as well as interactions between predatory animals and prey. Rapidly determining the activity of toxins is the main bottleneck in venomics discovery, but some recent bioinformatics and molecular modeling approaches give hope that accurate predictions of toxin specificity could be made in the near future.

The Processed Amino-Terminal Fragment of Human TLR7 Acts as a Chaperone To Direct Human TLR7 into Endosomes

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Shepherd, Dawn; Booth, Sarah; Waithe, Dominic; Reis e Sousa, Caetano

2015-01-01

TLR7 mediates innate immune responses to viral RNA in endocytic compartments. Mouse and human (h)TLR7 undergo proteolytic cleavage, resulting in the generation of a C-terminal fragment that accumulates in endosomes and associates with the signaling adaptor MyD88 upon receptor triggering by TLR7 agonists. Although mouse TLR7 is cleaved in endosomes by acidic proteases, hTLR7 processing can occur at neutral pH throughout the secretory pathway through the activity of furin-like proprotein convertases. However, the mechanisms by which cleaved hTLR7 reaches the endosomal compartment remain unclear. In this study, we demonstrate that, after hTLR7 proteolytic processing, the liberated amino (N)-terminal fragment remains bound to the C terminus through disulfide bonds and provides key trafficking information that ensures correct delivery of the complex to endosomal compartments. In the absence of the N-terminal fragment, the C-terminal fragment is redirected to the cell surface, where it is functionally inactive. Our data reveal a novel role for the N terminus of hTLR7 as a molecular chaperone that provides processed hTLR7 with the correct targeting instructions to reach the endosomal compartment, hence ensuring its biological activity and preventing inadvertent cell surface responses to self-RNA. PMID:25917086

PCSK9 and triglyceride-rich lipoprotein metabolism.

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Druce, I; Abujrad, H; Ooi, T C

2015-07-20

Pro-protein convertase subtilisin-kexin 9 (PCSK9) is known to affect low-density lipoprotein (LDL) metabolism, but there are indications from several lines of research that it may also influence the metabolism of other lipoproteins, especially triglyceride-rich lipoproteins (TRL). This review summarizes the current data on this possible role of PCSK9. A link between PCSK9 and TRL has been suggested through the demonstration of (1) a correlation between plasma PCSK9 and triglyceride (TG) levels in health and disease, (2) a correlation between plasma PCSK9 and markers of carbohydrate metabolism, which is closely related to TG metabolism, (3) an effect of TG-lowering fibrate therapy on plasma PCSK9 levels, (4) an effect of PCSK9 on postprandial lipemia, (5) an effect of PCSK9 on adipose tissue biology, (6) an effect of PCSK9 on apolipoprotein B production from the liver and intestines, (7) an effect of PCSK9 on receptors other than low density lipoprotein receptor (LDLR) that are involved in TRL metabolism, and (8) an effect of anti-PCSK9 therapy on serum TG levels. The underlying mechanisms are unclear but starting to emerge. © 2015 the Journal of Biomedical Research. All rights reserved.

Statin non-adherence and residual cardiovascular risk: There is need for substantial improvement.

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Banach, Maciej; Stulc, Tomas; Dent, Ricardo; Toth, Peter P

2016-12-15

Although statin therapy has proven to be the cornerstone for prevention and treatment of cardiovascular disease (CVD), there are many patients for whom long-term therapy remains suboptimal. The aims of this article are to review the current complex issues associated with statin use and to explore when novel treatment approaches should be considered. Statin discontinuation as well as adherence to statin therapy remain two of the greatest challenges for lipidologists. Evidence suggests that between 40 and 75% of patients discontinue their statin therapy within one year after initiation. Furthermore, whilst the reasons for persistence with statin therapy are complex, evidence shows that low-adherence to statins negatively impacts clinical outcomes and residual CV risk remains a major concern. Non-adherence or lack of persistence with long-term statin therapy in real-life may be the main cause of inadequate low density lipoprotein cholesterol lowering with statins. There is a large need for the improvement of the use of statins, which have good safety profiles and are inexpensive. On the other hand, in a non-cost-constrained environment, proprotein convertase subtilisin/kexin type 9 inhibitors should arguably be used more often in those patients in whom treatment with statins remains unsatisfactory. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Thematic review series: patient-oriented research. What we have learned about VLDL and LDL metabolism from human kinetics studies.

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Parhofer, Klaus G; Barrett, P Hugh R

2006-08-01

Lipoprotein metabolism is the result of a complex network of many individual components. Abnormal lipoprotein concentrations can result from changes in the production, conversion, or catabolism of lipoprotein particles. Studies in hypolipoproteinemia and hyperlipoproteinemia have elucidated the processes that control VLDL secretion as well as VLDL and LDL catabolism. Here, we review the current knowledge regarding apolipoprotein B (apoB) metabolism, focusing on selected clinically relevant conditions. In hypobetalipoproteinemia attributable to truncations in apoB, the rate of secretion is closely linked to the length of apoB. On the other hand, in patients with the metabolic syndrome, it appears that substrate, in the form of free fatty acids, coupled to the state of insulin resistance can induce hypersecretion of VLDL-apoB. Studies in patients with familial hypercholesterolemia, familial defective apoB, and mutant forms of proprotein convertase subtilisin/kexin type 9 show that mutations in the LDL receptor, the ligand for the receptor, or an intracellular chaperone for the receptor are the most important determinants in regulating LDL catabolism. This review also demonstrates the variance of results within similar, or even the same, phenotypic conditions. This underscores the sensitivity of metabolic studies to methodological aspects and thus the importance of the inclusion of adequate controls in studies.

Functional and clinical relevance of novel and known PCSK1 variants for childhood obesity and glucose metabolism

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Dennis Löffler

2017-03-01

Full Text Available Objective: Variants in Proprotein Convertase Subtilisin/Kexin Type 1 (PCSK1 may be causative for obesity as suggested by monogenic cases and association studies. Here we assessed the functional relevance in experimental studies and the clinical relevance through detailed metabolic phenotyping of newly identified and known PCSK1 variants in children. Results: In 52 obese children selected for elevated proinsulin levels and/or impaired glucose tolerance, we found eight known variants and two novel heterozygous variants (c.1095 + 1G > A and p.S24C by sequencing the PCSK1 gene. Patients with the new variants presented with extreme obesity, impaired glucose tolerance, and PCOS. Functionally, c.1095 + 1G > A caused skipping of exon8 translation and a complete loss of enzymatic activity. The protein was retained within the endoplasmic reticulum (ER causing ER stress. The p.S24C variant had no functional effect on protein size, cell trafficking, or enzymatic activity. The known variants rs6230, rs35753085, and rs725522 in the 5′ end did not affect PCSK1 promoter activity.In clinical association studies in 1673 lean and obese children, we confirmed associations of rs6232 and rs6234 with BMI-SDS and of rs725522 with glucose stimulated insulin secretion and Matsuda index. We did not find the new variants in any other subjects. Conclusions: We identified and functionally characterized two rare novel PCSK1 variants of which c.1095 + 1G > A caused complete loss of protein function. In addition to confirming rs6232 and rs6234 in PCSK1 as polygenic risk variants for childhood obesity, we describe an association of rs725522 with insulin metabolism. Our results support the contribution of PCSK1 variants to obesity predisposition in children. Keywords: PCSK1, PC1/3, Obesity, Children, Prohormone convertase 1/3

Cleavage of a Neuroinvasive Human Respiratory Virus Spike Glycoprotein by Proprotein Convertases Modulates Neurovirulence and Virus Spread within the Central Nervous System.

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Alain Le Coupanec

Full Text Available Human coronaviruses (HCoV are respiratory pathogens that may be associated with the development of neurological diseases, in view of their neuroinvasive and neurotropic properties. The viral spike (S glycoprotein is a major virulence factor for several coronavirus species, including the OC43 strain of HCoV (HCoV-OC43. In an attempt to study the role of this protein in virus spread within the central nervous system (CNS and neurovirulence, as well as to identify amino acid residues important for such functions, we compared the sequence of the S gene found in the laboratory reference strain HCoV-OC43 ATCC VR-759 to S sequences of viruses detected in clinical isolates from the human respiratory tract. We identified one predominant mutation at amino acid 758 (from RRSR↓ G758 to RRSR↓R758, which introduces a putative furin-like cleavage (↓ site. Using a molecular cDNA infectious clone to generate a corresponding recombinant virus, we show for the first time that such point mutation in the HCoV-OC43 S glycoprotein creates a functional cleavage site between the S1 and S2 portions of the S protein. While the corresponding recombinant virus retained its neuroinvasive properties, this mutation led to decreased neurovirulence while potentially modifying the mode of virus spread, likely leading to a limited dissemination within the CNS. Taken together, these results are consistent with the adaptation of HCoV-OC43 to the CNS environment, resulting from the selection of quasi-species harboring mutations that lead to amino acid changes in viral genes, like the S gene in HCoV-OC43, which may contribute to a more efficient establishment of a less pathogenic but persistent CNS infection. This adaptative mechanism could potentially be associated with human encephalitis or other neurological degenerative pathologies.

Analysing and Comparing Encodability Criteria

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Kirstin Peters

2015-08-01

Full Text Available Encodings or the proof of their absence are the main way to compare process calculi. To analyse the quality of encodings and to rule out trivial or meaningless encodings, they are augmented with quality criteria. There exists a bunch of different criteria and different variants of criteria in order to reason in different settings. This leads to incomparable results. Moreover it is not always clear whether the criteria used to obtain a result in a particular setting do indeed fit to this setting. We show how to formally reason about and compare encodability criteria by mapping them on requirements on a relation between source and target terms that is induced by the encoding function. In particular we analyse the common criteria full abstraction, operational correspondence, divergence reflection, success sensitiveness, and respect of barbs; e.g. we analyse the exact nature of the simulation relation (coupled simulation versus bisimulation that is induced by different variants of operational correspondence. This way we reduce the problem of analysing or comparing encodability criteria to the better understood problem of comparing relations on processes.

Landscape encodings enhance optimization.

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Konstantin Klemm

Full Text Available Hard combinatorial optimization problems deal with the search for the minimum cost solutions (ground states of discrete systems under strong constraints. A transformation of state variables may enhance computational tractability. It has been argued that these state encodings are to be chosen invertible to retain the original size of the state space. Here we show how redundant non-invertible encodings enhance optimization by enriching the density of low-energy states. In addition, smooth landscapes may be established on encoded state spaces to guide local search dynamics towards the ground state.

Landscape Encodings Enhance Optimization

Science.gov (United States)

Klemm, Konstantin; Mehta, Anita; Stadler, Peter F.

2012-01-01

Hard combinatorial optimization problems deal with the search for the minimum cost solutions (ground states) of discrete systems under strong constraints. A transformation of state variables may enhance computational tractability. It has been argued that these state encodings are to be chosen invertible to retain the original size of the state space. Here we show how redundant non-invertible encodings enhance optimization by enriching the density of low-energy states. In addition, smooth landscapes may be established on encoded state spaces to guide local search dynamics towards the ground state. PMID:22496860

Stress as a mnemonic filter: Interactions between medial temporal lobe encoding processes and post-encoding stress.

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Ritchey, Maureen; McCullough, Andrew M; Ranganath, Charan; Yonelinas, Andrew P

2017-01-01

Acute stress has been shown to modulate memory for recently learned information, an effect attributed to the influence of stress hormones on medial temporal lobe (MTL) consolidation processes. However, little is known about which memories will be affected when stress follows encoding. One possibility is that stress interacts with encoding processes to selectively protect memories that had elicited responses in the hippocampus and amygdala, two MTL structures important for memory formation. There is limited evidence for interactions between encoding processes and consolidation effects in humans, but recent studies of consolidation in rodents have emphasized the importance of encoding "tags" for determining the impact of consolidation manipulations on memory. Here, we used functional magnetic resonance imaging in humans to test the hypothesis that the effects of post-encoding stress depend on MTL processes observed during encoding. We found that changes in stress hormone levels were associated with an increase in the contingency of memory outcomes on hippocampal and amygdala encoding responses. That is, for participants showing high cortisol reactivity, memories became more dependent on MTL activity observed during encoding, thereby shifting the distribution of recollected events toward those that had elicited relatively high activation. Surprisingly, this effect was generally larger for neutral, compared to emotionally negative, memories. The results suggest that stress does not uniformly enhance memory, but instead selectively preserves memories tagged during encoding, effectively acting as mnemonic filter. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

A model for visual memory encoding.

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Rodolphe Nenert

Full Text Available Memory encoding engages multiple concurrent and sequential processes. While the individual processes involved in successful encoding have been examined in many studies, a sequence of events and the importance of modules associated with memory encoding has not been established. For this reason, we sought to perform a comprehensive examination of the network for memory encoding using data driven methods and to determine the directionality of the information flow in order to build a viable model of visual memory encoding. Forty healthy controls ages 19-59 performed a visual scene encoding task. FMRI data were preprocessed using SPM8 and then processed using independent component analysis (ICA with the reliability of the identified components confirmed using ICASSO as implemented in GIFT. The directionality of the information flow was examined using Granger causality analyses (GCA. All participants performed the fMRI task well above the chance level (>90% correct on both active and control conditions and the post-fMRI testing recall revealed correct memory encoding at 86.33 ± 5.83%. ICA identified involvement of components of five different networks in the process of memory encoding, and the GCA allowed for the directionality of the information flow to be assessed, from visual cortex via ventral stream to the attention network and then to the default mode network (DMN. Two additional networks involved in this process were the cerebellar and the auditory-insular network. This study provides evidence that successful visual memory encoding is dependent on multiple modules that are part of other networks that are only indirectly related to the main process. This model may help to identify the node(s of the network that are affected by a specific disease processes and explain the presence of memory encoding difficulties in patients in whom focal or global network dysfunction exists.

A model for visual memory encoding.

Science.gov (United States)

Nenert, Rodolphe; Allendorfer, Jane B; Szaflarski, Jerzy P

2014-01-01

Memory encoding engages multiple concurrent and sequential processes. While the individual processes involved in successful encoding have been examined in many studies, a sequence of events and the importance of modules associated with memory encoding has not been established. For this reason, we sought to perform a comprehensive examination of the network for memory encoding using data driven methods and to determine the directionality of the information flow in order to build a viable model of visual memory encoding. Forty healthy controls ages 19-59 performed a visual scene encoding task. FMRI data were preprocessed using SPM8 and then processed using independent component analysis (ICA) with the reliability of the identified components confirmed using ICASSO as implemented in GIFT. The directionality of the information flow was examined using Granger causality analyses (GCA). All participants performed the fMRI task well above the chance level (>90% correct on both active and control conditions) and the post-fMRI testing recall revealed correct memory encoding at 86.33 ± 5.83%. ICA identified involvement of components of five different networks in the process of memory encoding, and the GCA allowed for the directionality of the information flow to be assessed, from visual cortex via ventral stream to the attention network and then to the default mode network (DMN). Two additional networks involved in this process were the cerebellar and the auditory-insular network. This study provides evidence that successful visual memory encoding is dependent on multiple modules that are part of other networks that are only indirectly related to the main process. This model may help to identify the node(s) of the network that are affected by a specific disease processes and explain the presence of memory encoding difficulties in patients in whom focal or global network dysfunction exists.

Encoding of coordination complexes with XML.

Science.gov (United States)

Vinoth, P; Sankar, P

2017-09-01

An in-silico system to encode structure, bonding and properties of coordination complexes is developed. The encoding is achieved through a semantic XML markup frame. Composition of the coordination complexes is captured in terms of central atom and ligands. Structural information of central atom is detailed in terms of electron status of valence electron orbitals. The ligands are encoded with specific reference to the electron environment of ligand centre atoms. Behaviour of ligands to form low or high spin complexes is accomplished by assigning a Ligand Centre Value to every ligand based on the electronic environment of ligand centre atom. Chemical ontologies are used for categorization purpose and to control different hybridization schemes. Complexes formed by the central atoms of transition metal, non-transition elements belonging to s-block, p-block and f-block are encoded with a generic encoding platform. Complexes of homoleptic, heteroleptic and bridged types are also covered by this encoding system. Utility of the encoded system to predict redox electron transfer reaction in the coordination complexes is demonstrated with a simple application. Copyright © 2017 Elsevier Inc. All rights reserved.

Optimal higher-order encoder time-stamping

NARCIS (Netherlands)

Merry, R.J.E.; Molengraft, van de M.J.G.; Steinbuch, M.

2013-01-01

Optical incremental encoders are used to measure the position of motion control systems. The accuracy of the position measurement is determined and bounded by the number of slits on the encoder. The position measurement is affected by quantization errors and encoder imperfections. In this paper, an

Prohormone convertase 2 activity is increased in the hippocampus of Wfs1 knockout mice

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Karin eTein

2015-08-01

Full Text Available BackgroundMutations in WFS1 gene cause Wolfram syndrome, which is a rare autosomal recessive disorder, characterized by diabetes insipidus, diabetes mellitus, optic nerve atrophy and deafness (DIDMOAD. The WFS1 gene product wolframin is located in the endoplasmic reticulum. Mice lacking this gene exhibit disturbances in the processing and secretion of peptides, such as vasopressin and insulin. In the brain, high levels of the wolframin protein have been observed in the hippocampus, amygdala and limbic structures. The aim of this study was to investigate the effect of Wfs1 knockout on peptide processing in mouse hippocampus. A peptidomic approach was used to characterize individual peptides in the hippocampus of wild-type and Wfs1 knockout mice. ResultsWe identified 126 peptides in hippocampal extracts and the levels of 10 peptides differed between Wfs1 KO and wild-type mice at P<0.05. The peptide with the largest alteration was little-LEN, which level was 25 times higher in the hippocampus of Wfs1 KO mice compared to wild-type mice. Processing (cleavage of little-LEN from the Pcsk1n gene product proSAAS involves prohormone convertase 2 (PC2. Thus, PC2 activity was measured in extracts prepared from the hippocampus of Wfs1 knockout mice. The activity of PC2 in Wfs1 mutant mice was significantly higher (149.9±2.3%, p<0.0001, n=8 than in wild-type mice (100.0±7.0%, n=8. However, Western blot analysis showed that protein levels of 7B2, proPC2 and PC2 were same in both groups, and so were gene expression levels.ConclusionsProcessing of proSAAS is altered in the hippocampus of Wfs1-KO mice, which is caused by increased activity of PC2. Increased activity of PC2 in Wfs1 knockout mice is not caused by alteration in the levels of PC2 protein. Our results suggest a functional link between Wfs1 and PC2. Thus, the detailed molecular mechanism of the role of Wfs1 in the regulation of PC2 activity needs further investigation.

Emotional arousal and memory after deep encoding.

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Leventon, Jacqueline S; Camacho, Gabriela L; Ramos Rojas, Maria D; Ruedas, Angelica

2018-05-22

Emotion often enhances long-term memory. One mechanism for this enhancement is heightened arousal during encoding. However, reducing arousal, via emotion regulation (ER) instructions, has not been associated with reduced memory. In fact, the opposite pattern has been observed: stronger memory for emotional stimuli encoded with an ER instruction to reduce arousal. This pattern may be due to deeper encoding required by ER instructions. In the current research, we examine the effects of emotional arousal and deep-encoding on memory across three studies. In Study 1, adult participants completed a writing task (deep-encoding) for encoding negative, neutral, and positive picture stimuli, whereby half the emotion stimuli had the ER instruction to reduce the emotion. Memory was strong across conditions, and no memory enhancement was observed for any condition. In Study 2, adult participants completed the same writing task as Study 1, as well as a shallow-encoding task for one-third of negative, neutral, and positive trials. Memory was strongest for deep vs. shallow encoding trials, with no effects of emotion or ER instruction. In Study 3, adult participants completed a shallow-encoding task for negative, neutral, and positive stimuli, with findings indicating enhanced memory for negative emotional stimuli. Findings suggest that deep encoding must be acknowledged as a source of memory enhancement when examining manipulations of emotion-related arousal. Copyright © 2018. Published by Elsevier B.V.

Tranexamic acid suppresses ultraviolet B eye irradiation-induced melanocyte activation by decreasing the levels of prohormone convertase 2 and alpha-melanocyte-stimulating hormone.

Science.gov (United States)

Hiramoto, Keiichi; Yamate, Yurika; Sugiyama, Daijiro; Takahashi, Yumi; Mafune, Eiichi

2014-12-01

Tranexamic acid (trans-4-aminomethylcyclohexanecarboxylic acid) is a medicinal amino acid used in skin whitening care. This study examined the effects of tranexamic acid on the melanocyte activation of the skin induced by an ultraviolet (UV) B eye irradiation. The eye or ear was locally exposed to UVB at a dose of 1.0 kJ/m(2) using a 20SE sunlamp after covering the remaining body surface with aluminum foil. UVB eye irradiation induced melanocyte activation of the skin, similar to that observed following UVB ear irradiation, which was suppressed by the administration of tranexamic acid treatment. The plasma α-melanocyte-stimulating hormone (α-MSH) content was increased by UVB irradiation of the eye; however, the increase in α-MSH was suppressed by tranexamic acid treatment. In addition, UVB eye irradiation induced the up-regulation of prohormone convertase (PC) 2 in the pituitary gland. Meanwhile, the increase in PC2 induced by UVB eye irradiation was suppressed by tranexamic acid treatment. These results clearly indicate that tranexamic acid decreases the expression of PC2, which cleavages from proopiomelanocortin to α-MSH in the pituitary gland, thereby suppressing melanocyte activation. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Multidimensionally encoded magnetic resonance imaging.

Science.gov (United States)

Lin, Fa-Hsuan

2013-07-01

Magnetic resonance imaging (MRI) typically achieves spatial encoding by measuring the projection of a q-dimensional object over q-dimensional spatial bases created by linear spatial encoding magnetic fields (SEMs). Recently, imaging strategies using nonlinear SEMs have demonstrated potential advantages for reconstructing images with higher spatiotemporal resolution and reducing peripheral nerve stimulation. In practice, nonlinear SEMs and linear SEMs can be used jointly to further improve the image reconstruction performance. Here, we propose the multidimensionally encoded (MDE) MRI to map a q-dimensional object onto a p-dimensional encoding space where p > q. MDE MRI is a theoretical framework linking imaging strategies using linear and nonlinear SEMs. Using a system of eight surface SEM coils with an eight-channel radiofrequency coil array, we demonstrate the five-dimensional MDE MRI for a two-dimensional object as a further generalization of PatLoc imaging and O-space imaging. We also present a method of optimizing spatial bases in MDE MRI. Results show that MDE MRI with a higher dimensional encoding space can reconstruct images more efficiently and with a smaller reconstruction error when the k-space sampling distribution and the number of samples are controlled. Copyright © 2012 Wiley Periodicals, Inc.

Serum PCSK9 Levels Distinguish Individuals Who Do Not Respond to High-Dose Statin Therapy with the Expected Reduction in LDL-C

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Beth A. Taylor

2014-01-01

Full Text Available The purpose of the present report was to examine whether proprotein convertase subtilisin/kexin type 9 (PCSK9 levels differ in individuals who do not exhibit expected reductions in low density lipoprotein cholesterol (LDL-C with statin therapy. Eighteen nonresponder subjects treated with 80 mg atorvastatin treatment for 6 months without substantial reductions in LDL-C (ΔLDL-C: 2.6 ± 11.4% were compared to age- and gender-matched atorvastatin responders (ΔLDL-C: 50.7 ± 8.5% and placebo-treated subjects (ΔLDL-C: 9.9 ± 21.5%. Free PCSK9 was marginally higher in nonresponders at baseline (P=0.07 and significantly higher in atorvastatin responders after 6 months of treatment (P=0.04. The change in free PCSK9 over 6 months with statin treatment was higher (P<0.01 in atorvastatin responders (134.2 ± 131.5 ng/mL post- versus prestudy than in either the nonresponders (39.9 ± 87.8 ng/mL or placebo subjects (27.8 ± 97.6 ng/mL. Drug compliance was not lower in the nonresponders as assessed by pill counts and poststudy plasma atorvastatin levels. Serum PCSK9 levels, both at baseline and in response to statin therapy, may differentiate individuals who do versus those who do not respond to statin treatment.

Inhibition of Lassa virus glycoprotein cleavage and multicycle replication by site 1 protease-adapted alpha(1-antitrypsin variants.

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Anna Maisa

2009-06-01

Full Text Available Proteolytic processing of the Lassa virus envelope glycoprotein precursor GP-C by the host proprotein convertase site 1 protease (S1P is a prerequisite for the incorporation of the subunits GP-1 and GP-2 into viral particles and, hence, essential for infectivity and virus spread. Therefore, we tested in this study the concept of using S1P as a target to block efficient virus replication.We demonstrate that stable cell lines inducibly expressing S1P-adapted alpha(1-antitrypsin variants inhibit the proteolytic maturation of GP-C. Introduction of the S1P recognition motifs RRIL and RRLL into the reactive center loop of alpha(1-antitrypsin resulted in abrogation of GP-C processing by endogenous S1P to a similar level observed in S1P-deficient cells. Moreover, S1P-specific alpha(1-antitrypsins significantly inhibited replication and spread of a replication-competent recombinant vesicular stomatitis virus expressing the Lassa virus glycoprotein GP as well as authentic Lassa virus. Inhibition of viral replication correlated with the ability of the different alpha(1-antitrypsin variants to inhibit the processing of the Lassa virus glycoprotein precursor.Our data suggest that glycoprotein cleavage by S1P is a promising target for the development of novel anti-arenaviral strategies.

Emerging biologic therapies for hypercholesterolaemia.

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Pucci, Giacomo; Cicero, Arrigo F; Borghi, Claudio; Schillaci, Giuseppe

2017-09-01

LDL-cholesterol (LDL-C) is one of the most well-established risk factors for CV disease. Indeed, therapies that decrease LDL-C are proven to effectively reduce the risk of atherosclerotic CV disease. Monoclonal antibodies (mAbs) that target proprotein convertase subtilisin/kexin type 9 (PCSK9) have recently gained traction as a promising therapeutic strategy. Areas covered: In this review, the authors discuss the effectiveness of mAbs against PCSK9 in lowering low-density lipoprotein cholesterol (LDL-C) and other atherogenic lipid fractions. The discontinuation in the development of bococizumab due to efficacy and safety concerns, and the initial promising data about inclisiran, a long-acting small inhibiting RNA molecule against PCSK9 synthesis, is also discussed. Expert opinion: Initial data about cardiovascular (CV) outcomes in large scale, long-term studies suggest a possible further therapeutic pathway for LDL-C reduction, and currently support the notion that further LDL-C reduction, obtained with PCSK9 inhibition on top of best available therapy, provides increased CV protection in subjects at very high CV risk. The development and marketing of mAbs against PCSK9 could help to redefine current therapeutic strategies aimed at reducing cardiovascular (CV) morbidity and risk, through the reduction of LDL-C concentrations. The cost-effectiveness of these emerging drugs is yet to be established.

Genetics of Dyslipidemia and Ischemic Heart Disease.

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Sharma, Kavita; Baliga, Ragavendra R

2017-05-01

Genetic dyslipidemias contribute to the prevalence of ischemic heart disease. The field of genetic dyslipidemias and their influence on atherosclerotic heart disease is rapidly developing and accumulating increasing evidence. The purpose of this review is to describe the current state of knowledge in regard to inherited atherogenic dyslipidemias. The disorders of familial hypercholesterolemia (FH) and elevated lipoprotein(a) will be detailed. Genetic technology has made rapid advancements, leading to new discoveries in inherited atherogenic dyslipidemias, which will be explored in this review, as well as a description of possible future developments. Increasing attention has come upon the genetic disorders of familial hypercholesterolemia and elevated lipoprotein(a). This review includes new knowledge of these disorders including description of these disorders, their method of diagnosis, their prevalence, their genetic underpinnings, and their effect on the development of cardiovascular disease. In addition, it discusses major advances in genetic technology, including the completion of the human genome sequence, next-generation sequencing, and genome-wide association studies. Also discussed are rare variant studies with specific genetic mechanisms involved in inherited dyslipidemias, such as in the proprotein convertase subtilisin/kexin type 9 (PCSK9) enzyme. The field of genetics of dyslipidemia and cardiovascular disease is rapidly growing, which will result in a bright future of novel mechanisms of action and new therapeutics.

Parallel encoders for pixel detectors

International Nuclear Information System (INIS)

Nikityuk, N.M.

1991-01-01

A new method of fast encoding and determining the multiplicity and coordinates of fired pixels is described. A specific example construction of parallel encodes and MCC for n=49 and t=2 is given. 16 refs.; 6 figs.; 2 tabs

An Intensional Concurrent Faithful Encoding of Turing Machines

Directory of Open Access Journals (Sweden)

Thomas Given-Wilson

2014-10-01

Full Text Available The benchmark for computation is typically given as Turing computability; the ability for a computation to be performed by a Turing Machine. Many languages exploit (indirect encodings of Turing Machines to demonstrate their ability to support arbitrary computation. However, these encodings are usually by simulating the entire Turing Machine within the language, or by encoding a language that does an encoding or simulation itself. This second category is typical for process calculi that show an encoding of lambda-calculus (often with restrictions that in turn simulates a Turing Machine. Such approaches lead to indirect encodings of Turing Machines that are complex, unclear, and only weakly equivalent after computation. This paper presents an approach to encoding Turing Machines into intensional process calculi that is faithful, reduction preserving, and structurally equivalent. The encoding is demonstrated in a simple asymmetric concurrent pattern calculus before generalised to simplify infinite terms, and to show encodings into Concurrent Pattern Calculus and Psi Calculi.

Blind encoding into qudits

International Nuclear Information System (INIS)

Shaari, J.S.; Wahiddin, M.R.B.; Mancini, S.

2008-01-01

We consider the problem of encoding classical information into unknown qudit states belonging to any basis, of a maximal set of mutually unbiased bases, by one party and then decoding by another party who has perfect knowledge of the basis. Working with qudits of prime dimensions, we point out a no-go theorem that forbids 'shift' operations on arbitrary unknown states. We then provide the necessary conditions for reliable encoding/decoding

Encoder designed to work in harsh environments

Energy Technology Data Exchange (ETDEWEB)

Toop, L.

2007-05-15

Dynapar has developed the Acuro AX71 absolute encoder for use on offshore or land-based oil rig operations. It provides feedback on the operation of automated systems such as draw works, racking systems, rotary tables and top drives. By ensuring that automated systems function properly, this encoder responds to a need by the oil and gas industry to keep workers safe and improve efficiency, particularly for operations in rugged situations. The encoder provides feedback from motor systems to controllers, giving information about position and speed of downhole drill bits. This newly developed encoder is better than commonly used incremental encoders which are not precise in strong electrical noise environments. Rather, the absolute encoder uses a different method of reporting to the controller. A digital signal is transmitted constantly as the device operates. It is less susceptible to noise issues. It is highly accurate, tolerant of noise and is not affected by power outages. However, the absolute encoder is generally more delicate in drilling applications with high ambient temperatures and shock levels. Dynapar addressed this issue by developing compact stainless steel housing that is useful for corrosion resistance in marine applications. The AX71 absolute encoder can withstand up to 100 G of mechanical shock and ambient temperatures of up to 60 degrees C. The encoder is ATEX certified without barriers, and offers the high resolution feedback of 4,000 counts of multiturn rotation and 16,000 counts of position. 1 fig.

Pituitary adenylate cyclase-activating polypeptide precursor is processed solely by prohormone convertase 4 in the gonads.

Science.gov (United States)

Li, M; Mbikay, M; Arimura, A

2000-10-01

Pituitary adenylate cyclase-activating polypeptide (PACAP) is abundant not only in the brain, but also in the testis. Immunohistochemical studies have shown that PACAP-LI in rat testis is expressed stage specifically in spermatids. This suggests that testicular PACAP participates in the regulatory mechanism of spermatogenesis. Additionally, the ovary contains a relatively small amount of PACAP, conceivably involved in the regulation of folliculogenesis. PACAP is synthesized as a preprohormone and is processed by prohormone convertases, such as PC1, PC2, and PC4. PC4 is expressed only in the testis and ovary, where neither PC1 nor PC2 is expressed. However, whether PC4 is the sole endoprotease for the PACAP precursor in the gonads remains unknown. Recent studies using PC4-transgenic mice revealed that male PC4-null mice exhibited severely impaired fertility, although spermatogenesis appeared to be normal. The female PC4-null mice exhibited delayed folliculogenesis in the ovaries. To examine whether PC4 is the sole processing enzyme for the PACAP precursor in the gonads, we analyzed testicular and ovarian extracts from the PC4-null and wild-type mice for PACAP (PACAP38 and PACAP27) and its messenger RNA using reverse phase HPLC combined with specific RIAs and ribonuclease protection assay, respectively. For RIAs, three different polyclonal antisera with different recognition sites were used to identify PACAP38, PACAP27, and its precursor. Neither the testis nor the ovary from the PC4-null mice expressed PACAP38 or PACAP27, but the levels of PACAP transcripts in the testis and ovary of homozygous PC4-deficient mice were considerably elevated compared with those of the wild-type and heterozygous animals. The findings indicate that PC4 is the sole processing enzyme for the precursor of PACAP in the testis and ovary of mice. The possibility that the absence of bioactive PACAP in the testis and ovary of PC4-null mice caused severely impaired fertility in the males and

Linkage of congenital isolated adrenocorticotropic hormone deficiency to the corticotropin releasing hormone locus using simple sequence repeat polymorphisms

Energy Technology Data Exchange (ETDEWEB)

Kyllo, J.H.; Collins, M.M.; Vetter, K.L. [Univ. of Iowa College of Medicine, Iowa City, IA (United States)] [and others

1996-03-29

Genetic screening techniques using simple sequence repeat polymorphisms were applied to investigate the molecular nature of congenital isolated adrenocorticotropic hormone (ACTH) deficiency. We hypothesize that this rare cause of hypocortisolism shared by a brother and sister with two unaffected sibs and unaffected parents is inherited as an autosomal recessive single gene mutation. Genes involved in the hypothalamic-pituitary axis controlling cortisol sufficiency were investigated for a causal role in this disorder. Southern blotting showed no detectable mutations of the gene encoding pro-opiomelanocortin (POMC), the ACTH precursor. Other candidate genes subsequently considered were those encoding neuroendocrine convertase-1, and neuroendocrine convertase-2 (NEC-1, NEC-2), and corticotropin releasing hormone (CRH). Tests for linkage were performed using polymorphic di- and tetranucleotide simple sequence repeat markers flanking the reported map locations for POMC, NEC-1, NEC-2, and CRH. The chromosomal haplotypes determined by the markers flanking the loci for POMC, NEC-1, and NEC-2 were not compatible with linkage. However, 22 individual markers defining the chromosomal haplotypes flanking CRH were compatible with linkage of the disorder to the immediate area of this gene of chromosome 8. Based on these data, we hypothesize that the ACTH deficiency in this family is due to an abnormality of CRH gene structure or expression. These results illustrate the useful application of high density genetic maps constructed with simple sequence repeat markers for inclusion/exclusion studies of candidate genes in even very small nuclear families segregating for unusual phenotypes. 25 refs., 5 figs., 2 tabs.

Chemical Space of DNA-Encoded Libraries.

Science.gov (United States)

Franzini, Raphael M; Randolph, Cassie

2016-07-28

In recent years, DNA-encoded chemical libraries (DECLs) have attracted considerable attention as a potential discovery tool in drug development. Screening encoded libraries may offer advantages over conventional hit discovery approaches and has the potential to complement such methods in pharmaceutical research. As a result of the increased application of encoded libraries in drug discovery, a growing number of hit compounds are emerging in scientific literature. In this review we evaluate reported encoded library-derived structures and identify general trends of these compounds in relation to library design parameters. We in particular emphasize the combinatorial nature of these libraries. Generally, the reported molecules demonstrate the ability of this technology to afford hits suitable for further lead development, and on the basis of them, we derive guidelines for DECL design.

Video encoder/decoder for encoding/decoding motion compensated images

NARCIS (Netherlands)

1996-01-01

Video encoder and decoder, provided with a motion compensator for motion-compensated video coding or decoding in which a picture is coded or decoded in blocks in alternately horizontal and vertical steps. The motion compensator is provided with addressing means (160) and controlled multiplexers

Negative base encoding in optical linear algebra processors

Science.gov (United States)

Perlee, C.; Casasent, D.

1986-01-01

In the digital multiplication by analog convolution algorithm, the bits of two encoded numbers are convolved to form the product of the two numbers in mixed binary representation; this output can be easily converted to binary. Attention is presently given to negative base encoding, treating base -2 initially, and then showing that the negative base system can be readily extended to any radix. In general, negative base encoding in optical linear algebra processors represents a more efficient technique than either sign magnitude or 2's complement encoding, when the additions of digitally encoded products are performed in parallel.

Encoding entanglement-assisted quantum stabilizer codes

International Nuclear Information System (INIS)

Wang Yun-Jiang; Bai Bao-Ming; Li Zhuo; Xiao He-Ling; Peng Jin-Ye

2012-01-01

We address the problem of encoding entanglement-assisted (EA) quantum error-correcting codes (QECCs) and of the corresponding complexity. We present an iterative algorithm from which a quantum circuit composed of CNOT, H, and S gates can be derived directly with complexity O(n 2 ) to encode the qubits being sent. Moreover, we derive the number of each gate consumed in our algorithm according to which we can design EA QECCs with low encoding complexity. Another advantage brought by our algorithm is the easiness and efficiency of programming on classical computers. (general)

Data Encoding using Periodic Nano-Optical Features

Science.gov (United States)

Vosoogh-Grayli, Siamack

Successful trials have been made through a designed algorithm to quantize, compress and optically encode unsigned 8 bit integer values in the form of images using Nano optical features. The periodicity of the Nano-scale features (Nano-gratings) have been designed and investigated both theoretically and experimentally to create distinct states of variation (three on states and one off state). The use of easy to manufacture and machine readable encoded data in secured authentication media has been employed previously in bar-codes for bi-state (binary) models and in color barcodes for multiple state models. This work has focused on implementing 4 states of variation for unit information through periodic Nano-optical structures that separate an incident wavelength into distinct colors (variation states) in order to create an encoding system. Compared to barcodes and magnetic stripes in secured finite length storage media the proposed system encodes and stores more data. The benefits of multiple states of variation in an encoding unit are 1) increased numerically representable range 2) increased storage density and 3) decreased number of typical set elements for any ergodic or semi-ergodic source that emits these encoding units. A thorough investigation has targeted the effects of the use of multi-varied state Nano-optical features on data storage density and consequent data transmission rates. The results show that use of Nano-optical features for encoding data yields a data storage density of circa 800 Kbits/in2 via the implementation of commercially available high resolution flatbed scanner systems for readout. Such storage density is far greater than commercial finite length secured storage media such as Barcode family with maximum practical density of 1kbits/in2 and highest density magnetic stripe cards with maximum density circa 3 Kbits/in2. The numerically representable range of the proposed encoding unit for 4 states of variation is [0 255]. The number of

Molecular mechanisms for protein-encoded inheritance

Science.gov (United States)

Wiltzius, Jed J. W.; Landau, Meytal; Nelson, Rebecca; Sawaya, Michael R.; Apostol, Marcin I.; Goldschmidt, Lukasz; Soriaga, Angela B.; Cascio, Duilio; Rajashankar, Kanagalaghatta; Eisenberg, David

2013-01-01

Strains are phenotypic variants, encoded by nucleic acid sequences in chromosomal inheritance and by protein “conformations” in prion inheritance and transmission. But how is a protein “conformation” stable enough to endure transmission between cells or organisms? Here new polymorphic crystal structures of segments of prion and other amyloid proteins offer structural mechanisms for prion strains. In packing polymorphism, prion strains are encoded by alternative packings (polymorphs) of β-sheets formed by the same segment of a protein; in a second mechanism, segmental polymorphism, prion strains are encoded by distinct β-sheets built from different segments of a protein. Both forms of polymorphism can produce enduring “conformations,” capable of encoding strains. These molecular mechanisms for transfer of information into prion strains share features with the familiar mechanism for transfer of information by nucleic acid inheritance, including sequence specificity and recognition by non-covalent bonds. PMID:19684598

Beyond initial encoding: Measures of the post-encoding status of memory traces predict long-term recall in infancy

OpenAIRE

Pathman, Thanujeni; Bauer, Patricia J.

2012-01-01

The first years of life are witness to rapid changes in long-term recall ability. In the present research, we contributed to explanation of the changes by testing the absolute and relative contributions to long-term recall of encoding and post-encoding processes. Using elicited imitation, we sampled the status of 16-, 20-, and 24-month-old infants’ memory representations at various time points after experience of events. In Experiment 1, infants were tested immediately, 1 week after encoding,...

Dual beam encoded extended fractional Fourier transform security ...

Indian Academy of Sciences (India)

This paper describes a simple method for making dual beam encoded extended fractional Fourier transform (EFRT) security holograms. The hologram possesses different stages of encoding so that security features are concealed and remain invisible to the counterfeiter. These concealed and encoded anticounterfeit ...

The Arabic Diatessaron Project: Digitalizing, Encoding, Lemmatization

Directory of Open Access Journals (Sweden)

Giuliano Lancioni

2016-04-01

Full Text Available The Arabic Diatessaron Project (henceforth ADP is an international research project in Digital Humanities that aims to collect, digitalise and encode all known manuscripts of the Arabic Diatessaron (henceforth AD, a text that has been relatively neglected in scholarly research. ADP’s final goal is to provide a number of tools that can enable scholars to effectively query, compare and investigate all known variants of the text that will be encoded as far as possible in compliance with the Text Encoding Initiative (TEI guidelines. The paper addresses a number of issues involved in the process of digitalising manuscripts included in the two existing editions (Ciasca 1888 and Marmardji 1935, adding variants in unedited manuscripts, encoding and lemmatising the text. Issues involved in the design of the ADP include presentation of variants, choice of the standard text, applicability of TEI guidelines, automatic translation between different encodings, cross-edition concordances and principles of lemmatisation.

Using XML to encode TMA DES metadata

Directory of Open Access Journals (Sweden)

Oliver Lyttleton

2011-01-01

Full Text Available Background: The Tissue Microarray Data Exchange Specification (TMA DES is an XML specification for encoding TMA experiment data. While TMA DES data is encoded in XML, the files that describe its syntax, structure, and semantics are not. The DTD format is used to describe the syntax and structure of TMA DES, and the ISO 11179 format is used to define the semantics of TMA DES. However, XML Schema can be used in place of DTDs, and another XML encoded format, RDF, can be used in place of ISO 11179. Encoding all TMA DES data and metadata in XML would simplify the development and usage of programs which validate and parse TMA DES data. XML Schema has advantages over DTDs such as support for data types, and a more powerful means of specifying constraints on data values. An advantage of RDF encoded in XML over ISO 11179 is that XML defines rules for encoding data, whereas ISO 11179 does not. Materials and Methods: We created an XML Schema version of the TMA DES DTD. We wrote a program that converted ISO 11179 definitions to RDF encoded in XML, and used it to convert the TMA DES ISO 11179 definitions to RDF. Results: We validated a sample TMA DES XML file that was supplied with the publication that originally specified TMA DES using our XML Schema. We successfully validated the RDF produced by our ISO 11179 converter with the W3C RDF validation service. Conclusions: All TMA DES data could be encoded using XML, which simplifies its processing. XML Schema allows datatypes and valid value ranges to be specified for CDEs, which enables a wider range of error checking to be performed using XML Schemas than could be performed using DTDs.

Using XML to encode TMA DES metadata.

Science.gov (United States)

Lyttleton, Oliver; Wright, Alexander; Treanor, Darren; Lewis, Paul

2011-01-01

The Tissue Microarray Data Exchange Specification (TMA DES) is an XML specification for encoding TMA experiment data. While TMA DES data is encoded in XML, the files that describe its syntax, structure, and semantics are not. The DTD format is used to describe the syntax and structure of TMA DES, and the ISO 11179 format is used to define the semantics of TMA DES. However, XML Schema can be used in place of DTDs, and another XML encoded format, RDF, can be used in place of ISO 11179. Encoding all TMA DES data and metadata in XML would simplify the development and usage of programs which validate and parse TMA DES data. XML Schema has advantages over DTDs such as support for data types, and a more powerful means of specifying constraints on data values. An advantage of RDF encoded in XML over ISO 11179 is that XML defines rules for encoding data, whereas ISO 11179 does not. We created an XML Schema version of the TMA DES DTD. We wrote a program that converted ISO 11179 definitions to RDF encoded in XML, and used it to convert the TMA DES ISO 11179 definitions to RDF. We validated a sample TMA DES XML file that was supplied with the publication that originally specified TMA DES using our XML Schema. We successfully validated the RDF produced by our ISO 11179 converter with the W3C RDF validation service. All TMA DES data could be encoded using XML, which simplifies its processing. XML Schema allows datatypes and valid value ranges to be specified for CDEs, which enables a wider range of error checking to be performed using XML Schemas than could be performed using DTDs.

Using XML to encode TMA DES metadata

Science.gov (United States)

Lyttleton, Oliver; Wright, Alexander; Treanor, Darren; Lewis, Paul

2011-01-01

Background: The Tissue Microarray Data Exchange Specification (TMA DES) is an XML specification for encoding TMA experiment data. While TMA DES data is encoded in XML, the files that describe its syntax, structure, and semantics are not. The DTD format is used to describe the syntax and structure of TMA DES, and the ISO 11179 format is used to define the semantics of TMA DES. However, XML Schema can be used in place of DTDs, and another XML encoded format, RDF, can be used in place of ISO 11179. Encoding all TMA DES data and metadata in XML would simplify the development and usage of programs which validate and parse TMA DES data. XML Schema has advantages over DTDs such as support for data types, and a more powerful means of specifying constraints on data values. An advantage of RDF encoded in XML over ISO 11179 is that XML defines rules for encoding data, whereas ISO 11179 does not. Materials and Methods: We created an XML Schema version of the TMA DES DTD. We wrote a program that converted ISO 11179 definitions to RDF encoded in XML, and used it to convert the TMA DES ISO 11179 definitions to RDF. Results: We validated a sample TMA DES XML file that was supplied with the publication that originally specified TMA DES using our XML Schema. We successfully validated the RDF produced by our ISO 11179 converter with the W3C RDF validation service. Conclusions: All TMA DES data could be encoded using XML, which simplifies its processing. XML Schema allows datatypes and valid value ranges to be specified for CDEs, which enables a wider range of error checking to be performed using XML Schemas than could be performed using DTDs. PMID:21969921

Extreme expansion of NBS-encoding genes in Rosaceae.

Science.gov (United States)

Jia, YanXiao; Yuan, Yang; Zhang, Yanchun; Yang, Sihai; Zhang, Xiaohui

2015-05-03

Nucleotide binding site leucine-rich repeats (NBS-LRR) genes encode a large class of disease resistance (R) proteins in plants. Extensive studies have been carried out to identify and investigate NBS-encoding gene families in many important plant species. However, no comprehensive research into NBS-encoding genes in the Rosaceae has been performed. In this study, five whole-genome sequenced Rosaceae species, including apple, pear, peach, mei, and strawberry, were analyzed to investigate the evolutionary pattern of NBS-encoding genes and to compare them to those of three Cucurbitaceae species, cucumber, melon, and watermelon. Considerable differences in the copy number of NBS-encoding genes were observed between Cucurbitaceae and Rosaceae species. In Rosaceae species, a large number and a high proportion of NBS-encoding genes were observed in peach (437, 1.52%), mei (475, 1.51%), strawberry (346, 1.05%) and pear (617, 1.44%), and apple contained a whopping 1303 (2.05%) NBS-encoding genes, which might be the highest number of R-genes in all of these reported diploid plant. However, no more than 100 NBS-encoding genes were identified in Cucurbitaceae. Many more species-specific gene families were classified and detected with the signature of positive selection in Rosaceae species, especially in the apple genome. Taken together, our findings indicate that NBS-encoding genes in Rosaceae, especially in apple, have undergone extreme expansion and rapid adaptive evolution. Useful information was provided for further research on the evolutionary mode of disease resistance genes in Rosaceae crops.

Aerobic Exercise During Encoding Impairs Hippocampus-Dependent Memory.

Science.gov (United States)

Soga, Keishi; Kamijo, Keita; Masaki, Hiroaki

2017-08-01

We investigated how aerobic exercise during encoding affects hippocampus-dependent memory through a source memory task that assessed hippocampus-independent familiarity and hippocampus-dependent recollection processes. Using a within-participants design, young adult participants performed a memory-encoding task while performing a cycling exercise or being seated. The subsequent retrieval phase was conducted while sitting on a chair. We assessed behavioral and event-related brain potential measures of familiarity and recollection processes during the retrieval phase. Results indicated that source accuracy was lower for encoding with exercise than for encoding in the resting condition. Event-related brain potential measures indicated that the parietal old/new effect, which has been linked to recollection processing, was observed in the exercise condition, whereas it was absent in the rest condition, which is indicative of exercise-induced hippocampal activation. These findings suggest that aerobic exercise during encoding impairs hippocampus-dependent memory, which may be attributed to inefficient source encoding during aerobic exercise.

Convolutional over Recurrent Encoder for Neural Machine Translation

Directory of Open Access Journals (Sweden)

Dakwale Praveen

2017-06-01

Full Text Available Neural machine translation is a recently proposed approach which has shown competitive results to traditional MT approaches. Standard neural MT is an end-to-end neural network where the source sentence is encoded by a recurrent neural network (RNN called encoder and the target words are predicted using another RNN known as decoder. Recently, various models have been proposed which replace the RNN encoder with a convolutional neural network (CNN. In this paper, we propose to augment the standard RNN encoder in NMT with additional convolutional layers in order to capture wider context in the encoder output. Experiments on English to German translation demonstrate that our approach can achieve significant improvements over a standard RNN-based baseline.

Exploring the influence of encoding format on subsequent memory.

Science.gov (United States)

Turney, Indira C; Dennis, Nancy A; Maillet, David; Rajah, M Natasha

2017-05-01

Distinctive encoding is greatly influenced by gist-based processes and has been shown to suffer when highly similar items are presented in close succession. Thus, elucidating the mechanisms underlying how presentation format affects gist processing is essential in determining the factors that influence these encoding processes. The current study utilised multivariate partial least squares (PLS) analysis to identify encoding networks directly associated with retrieval performance in a blocked and intermixed presentation condition. Subsequent memory analysis for successfully encoded items indicated no significant differences between reaction time and retrieval performance and presentation format. Despite no significant behavioural differences, behaviour PLS revealed differences in brain-behaviour correlations and mean condition activity in brain regions associated with gist-based vs. distinctive encoding. Specifically, the intermixed format encouraged more distinctive encoding, showing increased activation of regions associated with strategy use and visual processing (e.g., frontal and visual cortices, respectively). Alternatively, the blocked format exhibited increased gist-based processes, accompanied by increased activity in the right inferior frontal gyrus. Together, results suggest that the sequence that information is presented during encoding affects the degree to which distinctive encoding is engaged. These findings extend our understanding of the Fuzzy Trace Theory and the role of presentation format on encoding processes.

Source-constrained retrieval influences the encoding of new information.

Science.gov (United States)

Danckert, Stacey L; MacLeod, Colin M; Fernandes, Myra A

2011-11-01

Jacoby, Shimizu, Daniels, and Rhodes (Psychonomic Bulletin & Review, 12, 852-857, 2005) showed that new words presented as foils among a list of old words that had been deeply encoded were themselves subsequently better recognized than new words presented as foils among a list of old words that had been shallowly encoded. In Experiment 1, by substituting a deep-versus-shallow imagery manipulation for the levels-of-processing manipulation, we demonstrated that the effect is robust and that it generalizes, also occurring with a different type of encoding. In Experiment 2, we provided more direct evidence for context-related encoding during tests of deeply encoded words, showing enhanced priming for foils presented among deeply encoded targets when participants made the same deep-encoding judgments on those items as had been made on the targets during study. In Experiment 3, we established that the findings from Experiment 2 are restricted to this specific deep judgment task and are not a general consequence of these foils being associated with deeply encoded items. These findings provide support for the source-constrained retrieval hypothesis of Jacoby, Shimizu, Daniels, and Rhodes: New information can be influenced by how surrounding items are encoded and retrieved, as long as the surrounding items recruit a coherent mode of processing.

PCSK9 Antibodies for the Treatment of Hypercholesterolemia

Directory of Open Access Journals (Sweden)

Ioanna Gouni-Berthold

2014-12-01

Full Text Available The serine protease proprotein convertase subtilisin/kexin type 9 (PCSK9 binds to the low-density lipoprotein (LDL receptor (LDLR and directs it to lysosomes for intracellular degradation. This results in decreased numbers of LDLR available on the hepatic cell surface to bind LDL particles and remove them from the circulation and therefore to a subsequent increase in circulating LDL-cholesterol (LDL-C plasma levels. Since 2003, when the role of PCSK9 in LDL-C metabolism was discovered, there have been major efforts to develop efficient and safe methods to inhibit it. Amongst those, monoclonal antibodies against PCSK9 are the furthest in development, with multiple phase 3 trials already published and with cardiovascular endpoint trials currently underway. Two fully human monoclonal antibodies, evolocumab (AMG 145 and alirocumab (REGN727/SAR236553, have been extensively studied in a wide range of subjects, such as those with statin intolerance, as an add-on to statin therapy, as a monotherapy and in patients with familial hypercholesterolemia. PCSK9 antibodies result in a consistent and robust decrease in LDL-C plasma levels ranging from 40% to 70%, either on top of statins or as a monotherapy. If the safety data from the on-going phase 3 trials remain as reassuring as the data available till now, PCSK9 antibodies will offer a novel, powerful therapeutic option to decrease LDL-C plasma levels and, hopefully, cardiovascular risk.

Inhibition of furin results in increased growth, invasiveness and cytokine production of synoviocytes from patients with rheumatoid arthritis.

Science.gov (United States)

Wu, Changshun; Song, Zezhong; Liu, Huiling; Pan, Jihong; Jiang, Huiyu; Liu, Chao; Yan, Zexing; Feng, Hong; Sun, Shui

2017-07-01

Fibroblast-like synoviocytes derived from patients with rheumatoid arthritis play a key role by local production of cytokines and proteolytic enzymes that degrade the extracellular matrix and cartilage. These synoviocytes acquire phenotypic characteristics commonly observed in transformed cells, like anchorage-independent growth, increased proliferation and invasiveness, and insensitivity to apoptosis. Furin is a ubiquitous proprotein convertase that is capable of cleaving precursors of a wide variety of proteins. In patients with rheumatoid arthritis, furin is reported to be highly expressed in the synovial pannus compared with healthy persons. However, the mechanisms are poorly understood. This study is to explore the effect of furin overexpression in rheumatoid synoviocytes. In this study, RNA interference was used to knock down furin expression and to assess the resultant effects on biological behaviors of synoviocytes, such as cell proliferation, invasion, migration, cell cycle and cell apoptosis. In addition, the production of inflammatory cytokines was evaluated. The results showed that the inhibition of furin enhanced proliferation, invasion, and migration of synoviocytes in vitro. Cell cycle was accelerated and cell death was affected by furin knockdown. Also, the inhibition of furin increased interleukin-1β and tumor necrosis factor-α secretion of synoviocytes. Inhibition of furin enhances invasive phenotype of synoviocytes from patients with rheumatoid arthritis, implying a protective role of furin. Agents targeting upregulation of furin may have therapeutic potential for rheumatoid arthritis. Copyright © 2016 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

PCSK9 at the crossroad of cholesterol metabolism and immune function during infections.

Science.gov (United States)

Paciullo, Francesco; Fallarino, Francesca; Bianconi, Vanessa; Mannarino, Massimo R; Sahebkar, Amirhossein; Pirro, Matteo

2017-09-01

Sepsis, a complex and dynamic syndrome resulting from microbial invasion and immune system dysregulation, is associated with an increased mortality, reaching up to 35% worldwide. Cholesterol metabolism is often disturbed during sepsis, with low plasma cholesterol levels being associated with poor prognosis. Proprotein convertase subtilisin/kexin type 9 (PCSK9) promotes degradation of the low-density lipoprotein receptor (LDLR), thus regulating intracellular and plasma cholesterol levels. PCSK9 is often upregulated during sepsis and might have a detrimental effect on immune host response and survival. Accordingly, PCSK9 reduces lipopolysaccharide uptake and clearance by human hepatocytes. Moreover, PCSK9 upregulation exacerbates organ dysfunction and tissue inflammation during sepsis, whereas a protective effect of PCSK9 deficiency has been documented in septic patients. Although a possible detrimental impact of PCSK9 on survival has been described, some beneficial effects of PCSK9 on immune response may be hypothesized. First, PCSK9 is associated with increased plasma cholesterol levels, which might be protective during sepsis. Second, PCSK9, by stimulating LDLR degradation and inhibiting reverse cholesterol transport (RCT), might promote preferential cholesterol accumulation in macrophages and other immune cells; these events might improve lipid raft composition and augment toll-like receptor function thus supporting inflammatory response. Hence, a more clear definition of the role of PCSK9 in septic states might provide additional insight in the understanding of the sepsis-associated immune dysregulation and enhance therapeutic outcomes. © 2017 Wiley Periodicals, Inc.

Circumventing furin enhances factor VIII biological activity and ameliorates bleeding phenotypes in hemophilia models

Science.gov (United States)

Siner, Joshua I.; Samelson-Jones, Benjamin J.; Crudele, Julie M.; French, Robert A.; Lee, Benjamin J.; Zhou, Shanzhen; Merricks, Elizabeth; Raymer, Robin; Camire, Rodney M.; Arruda, Valder R.

2016-01-01

Processing by the proprotein convertase furin is believed to be critical for the biological activity of multiple proteins involved in hemostasis, including coagulation factor VIII (FVIII). This belief prompted the retention of the furin recognition motif (amino acids 1645–1648) in the design of B-domain–deleted FVIII (FVIII-BDD) products in current clinical use and in the drug development pipeline, as well as in experimental FVIII gene therapy strategies. Here, we report that processing by furin is in fact deleterious to FVIII-BDD secretion and procoagulant activity. Inhibition of furin increases the secretion and decreases the intracellular retention of FVIII-BDD protein in mammalian cells. Our new variant (FVIII-ΔF), in which this recognition motif is removed, efficiently circumvents furin. FVIII-ΔF demonstrates increased recombinant protein yields, enhanced clotting activity, and higher circulating FVIII levels after adeno-associated viral vector–based liver gene therapy in a murine model of severe hemophilia A (HA) compared with FVIII-BDD. Moreover, we observed an amelioration of the bleeding phenotype in severe HA dogs with sustained therapeutic FVIII levels after FVIII-ΔF gene therapy at a lower vector dose than previously employed in this model. The immunogenicity of FVIII-ΔF did not differ from that of FVIII-BDD as a protein or a gene therapeutic. Thus, contrary to previous suppositions, FVIII variants that can avoid furin processing are likely to have enhanced translational potential for HA therapy. PMID:27734034

[Recommendations of the European Society of Cardiology and the European Atherosclerosis Society on Cardiovascular Disease Prevention and Management of Dyslipidemias. for the Diagnosis of Atherosclerosis and Dyslipidemia Treatment (2016): Basic S.G.

Science.gov (United States)

Bubnova, M G; Kukharchuk, V V

2017-03-01

This review summarizes the main provisions of the new, issued in 2016, recommendations of the European Society of Cardiology and Atherosclerosis Society in cooperation with the European Association on Cardiovascular Prevention and Rehabilitation on Cardiovascular disease prevention and Management of dyslipidemia. In these recommendations, the following trends can be traced distinctly: priority in primary prevention is given to non-drug methods of influence; targets of hypolipidemic therapy are identified not only for low density lipoprotein (LDL) cholesterol (CH), but also for non-high density lipoprotein (HDL) CH, especially in cases of concomitant hypertriglyceridemia. In the field of therapy, in which statins remain the main tool of correction of hyperlipidemia, it is recommended to more widely resort to the use of combination therapy, especially in cases of familial hypercholesterolemia or intolerance to statins; introduction of a new class of drugs- inhibitors of proprotein convertase subtilisin/kexin type 9 makes it possible to further reduce the level of LDLCH, lipoprotein(a) more than 60%. Regarding the wider application of these drugs there are issues related to the relatively limited experience of their use and the lack of data on long-term results and the incidence of side effects. Much attention is paid to more active correction of dyslipidemia in elderly patients, patients with chronic renal failure, diabetes, and several other diseases. The emergence of new European recommendations will undoubtedly serve as a stimulus to the revision of the Russian recommendations, which remain unchanged from 2012.

Hall effect encoding of brushless dc motors

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Berard, C. A.; Furia, T. J.; Goldberg, E. A.; Greene, R. C.

1970-01-01

Encoding mechanism integral to the motor and using the permanent magnets embedded in the rotor eliminates the need for external devices to encode information relating the position and velocity of the rotating member.

Multichannel compressive sensing MRI using noiselet encoding.

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Kamlesh Pawar

Full Text Available The incoherence between measurement and sparsifying transform matrices and the restricted isometry property (RIP of measurement matrix are two of the key factors in determining the performance of compressive sensing (CS. In CS-MRI, the randomly under-sampled Fourier matrix is used as the measurement matrix and the wavelet transform is usually used as sparsifying transform matrix. However, the incoherence between the randomly under-sampled Fourier matrix and the wavelet matrix is not optimal, which can deteriorate the performance of CS-MRI. Using the mathematical result that noiselets are maximally incoherent with wavelets, this paper introduces the noiselet unitary bases as the measurement matrix to improve the incoherence and RIP in CS-MRI. Based on an empirical RIP analysis that compares the multichannel noiselet and multichannel Fourier measurement matrices in CS-MRI, we propose a multichannel compressive sensing (MCS framework to take the advantage of multichannel data acquisition used in MRI scanners. Simulations are presented in the MCS framework to compare the performance of noiselet encoding reconstructions and Fourier encoding reconstructions at different acceleration factors. The comparisons indicate that multichannel noiselet measurement matrix has better RIP than that of its Fourier counterpart, and that noiselet encoded MCS-MRI outperforms Fourier encoded MCS-MRI in preserving image resolution and can achieve higher acceleration factors. To demonstrate the feasibility of the proposed noiselet encoding scheme, a pulse sequences with tailored spatially selective RF excitation pulses was designed and implemented on a 3T scanner to acquire the data in the noiselet domain from a phantom and a human brain. The results indicate that noislet encoding preserves image resolution better than Fouirer encoding.

Low Complexity HEVC Encoder for Visual Sensor Networks

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Zhaoqing Pan

2015-12-01

Full Text Available Visual sensor networks (VSNs can be widely applied in security surveillance, environmental monitoring, smart rooms, etc. However, with the increased number of camera nodes in VSNs, the volume of the visual information data increases significantly, which becomes a challenge for storage, processing and transmitting the visual data. The state-of-the-art video compression standard, high efficiency video coding (HEVC, can effectively compress the raw visual data, while the higher compression rate comes at the cost of heavy computational complexity. Hence, reducing the encoding complexity becomes vital for the HEVC encoder to be used in VSNs. In this paper, we propose a fast coding unit (CU depth decision method to reduce the encoding complexity of the HEVC encoder for VSNs. Firstly, the content property of the CU is analyzed. Then, an early CU depth decision method and a low complexity distortion calculation method are proposed for the CUs with homogenous content. Experimental results show that the proposed method achieves 71.91% on average encoding time savings for the HEVC encoder for VSNs.

Negative affect promotes encoding of and memory for details at the expense of the gist: affect, encoding, and false memories.

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Storbeck, Justin

2013-01-01

I investigated whether negative affective states enhance encoding of and memory for item-specific information reducing false memories. Positive, negative, and neutral moods were induced, and participants then completed a Deese-Roediger-McDermott (DRM) false-memory task. List items were presented in unique spatial locations or unique fonts to serve as measures for item-specific encoding. The negative mood conditions had more accurate memories for item-specific information, and they also had fewer false memories. The final experiment used a manipulation that drew attention to distinctive information, which aided learning for DRM words, but also promoted item-specific encoding. For the condition that promoted item-specific encoding, false memories were reduced for positive and neutral mood conditions to a rate similar to that of the negative mood condition. These experiments demonstrated that negative affective cues promote item-specific processing reducing false memories. People in positive and negative moods encode events differently creating different memories for the same event.

Evaluation of color encodings for high dynamic range pixels

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Boitard, Ronan; Mantiuk, Rafal K.; Pouli, Tania

2015-03-01

Traditional Low Dynamic Range (LDR) color spaces encode a small fraction of the visible color gamut, which does not encompass the range of colors produced on upcoming High Dynamic Range (HDR) displays. Future imaging systems will require encoding much wider color gamut and luminance range. Such wide color gamut can be represented using floating point HDR pixel values but those are inefficient to encode. They also lack perceptual uniformity of the luminance and color distribution, which is provided (in approximation) by most LDR color spaces. Therefore, there is a need to devise an efficient, perceptually uniform and integer valued representation for high dynamic range pixel values. In this paper we evaluate several methods for encoding colour HDR pixel values, in particular for use in image and video compression. Unlike other studies we test both luminance and color difference encoding in a rigorous 4AFC threshold experiments to determine the minimum bit-depth required. Results show that the Perceptual Quantizer (PQ) encoding provides the best perceptual uniformity in the considered luminance range, however the gain in bit-depth is rather modest. More significant difference can be observed between color difference encoding schemes, from which YDuDv encoding seems to be the most efficient.

Security enhanced BioEncoding for protecting iris codes

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Ouda, Osama; Tsumura, Norimichi; Nakaguchi, Toshiya

2011-06-01

Improving the security of biometric template protection techniques is a key prerequisite for the widespread deployment of biometric technologies. BioEncoding is a recently proposed template protection scheme, based on the concept of cancelable biometrics, for protecting biometric templates represented as binary strings such as iris codes. The main advantage of BioEncoding over other template protection schemes is that it does not require user-specific keys and/or tokens during verification. Besides, it satisfies all the requirements of the cancelable biometrics construct without deteriorating the matching accuracy. However, although it has been shown that BioEncoding is secure enough against simple brute-force search attacks, the security of BioEncoded templates against more smart attacks, such as record multiplicity attacks, has not been sufficiently investigated. In this paper, a rigorous security analysis of BioEncoding is presented. Firstly, resistance of BioEncoded templates against brute-force attacks is revisited thoroughly. Secondly, we show that although the cancelable transformation employed in BioEncoding might be non-invertible for a single protected template, the original iris code could be inverted by correlating several templates used in different applications but created from the same iris. Accordingly, we propose an important modification to the BioEncoding transformation process in order to hinder attackers from exploiting this type of attacks. The effectiveness of adopting the suggested modification is validated and its impact on the matching accuracy is investigated empirically using CASIA-IrisV3-Interval dataset. Experimental results confirm the efficacy of the proposed approach and show that it preserves the matching accuracy of the unprotected iris recognition system.

Deep and shallow encoding effects on face recognition: an ERP study.

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Marzi, Tessa; Viggiano, Maria Pia

2010-12-01

Event related potentials (ERPs) were employed to investigate whether and when brain activity related to face recognition varies according to the processing level undertaken at encoding. Recognition was assessed when preceded by a "shallow" (orientation judgement) or by a "deep" study task (occupation judgement). Moreover, we included a further manipulation by presenting at encoding faces either in the upright or inverted orientation. As expected, deeply encoded faces were recognized more accurately and more quickly with respect to shallowly encoded faces. The ERP showed three main findings: i) as witnessed by more positive-going potentials for deeply encoded faces, at early and later processing stage, face recognition was influenced by the processing strategy adopted during encoding; ii) structural encoding, indexed by the N170, turned out to be "cognitively penetrable" showing repetition priming effects for deeply encoded faces; iii) face inversion, by disrupting configural processing during encoding, influenced memory related processes for deeply encoded faces and impaired the recognition of faces shallowly processed. The present study adds weight to the concept that the depth of processing during memory encoding affects retrieval. We found that successful retrieval following deep encoding involved both familiarity- and recollection-related processes showing from 500 ms a fronto-parietal distribution, whereas shallow encoding affected only earlier processing stages reflecting perceptual priming. Copyright © 2010 Elsevier B.V. All rights reserved.

Review of Random Phase Encoding in Volume Holographic Storage

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Wei-Chia Su

2012-09-01

Full Text Available Random phase encoding is a unique technique for volume hologram which can be applied to various applications such as holographic multiplexing storage, image encryption, and optical sensing. In this review article, we first review and discuss diffraction selectivity of random phase encoding in volume holograms, which is the most important parameter related to multiplexing capacity of volume holographic storage. We then review an image encryption system based on random phase encoding. The alignment of phase key for decryption of the encoded image stored in holographic memory is analyzed and discussed. In the latter part of the review, an all-optical sensing system implemented by random phase encoding and holographic interconnection is presented.

New recombinant bacterium comprises a heterologous gene encoding glycerol dehydrogenase and/or an up-regulated native gene encoding glycerol dehydrogenase, useful for producing ethanol

DEFF Research Database (Denmark)

2010-01-01

dehydrogenase encoding region of the bacterium, or is inserted into a phosphotransacetylase encoding region of the bacterium, or is inserted into an acetate kinase encoding region of the bacterium. It is operably linked to an inducible, a regulated or a constitutive promoter. The up-regulated glycerol......TECHNOLOGY FOCUS - BIOTECHNOLOGY - Preparation (claimed): Producing recombinant bacterium having enhanced ethanol production characteristics when cultivated in growth medium comprising glycerol comprises: (a) transforming a parental bacterium by (i) the insertion of a heterologous gene encoding...... glycerol dehydrogenase; and/or (ii) up-regulating a native gene encoding glycerol dehydrogenase; and (b) obtaining the recombinant bacterium. Preferred Bacterium: In the recombinant bacterium above, the inserted heterologous gene and/or the up-regulated native gene is encoding a glycerol dehydrogenase...

Grammatical constraints on phonological encoding in speech production.

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Heller, Jordana R; Goldrick, Matthew

2014-12-01

To better understand the influence of grammatical encoding on the retrieval and encoding of phonological word-form information during speech production, we examine how grammatical class constraints influence the activation of phonological neighbors (words phonologically related to the target--e.g., MOON, TWO for target TUNE). Specifically, we compare how neighbors that share a target's grammatical category (here, nouns) influence its planning and retrieval, assessed by picture naming latencies, and phonetic encoding, assessed by word productions in picture names, when grammatical constraints are strong (in sentence contexts) versus weak (bare naming). Within-category (noun) neighbors influenced planning time and phonetic encoding more strongly in sentence contexts. This suggests that grammatical encoding constrains phonological processing; the influence of phonological neighbors is grammatically dependent. Moreover, effects on planning times could not fully account for phonetic effects, suggesting that phonological interaction affects articulation after speech onset. These results support production theories integrating grammatical, phonological, and phonetic processes.

Two Pathways to Stimulus Encoding in Category Learning?

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Davis, Tyler; Love, Bradley C.; Maddox, W. Todd

2008-01-01

Category learning theorists tacitly assume that stimuli are encoded by a single pathway. Motivated by theories of object recognition, we evaluate a dual-pathway account of stimulus encoding. The part-based pathway establishes mappings between sensory input and symbols that encode discrete stimulus features, whereas the image-based pathway applies holistic templates to sensory input. Our experiments use rule-plus-exception structures in which one exception item in each category violates a salient regularity and must be distinguished from other items. In Experiment 1, we find that discrete representations are crucial for recognition of exceptions following brief training. Experiments 2 and 3 involve multi-session training regimens designed to encourage either part or image-based encoding. We find that both pathways are able to support exception encoding, but have unique characteristics. We speculate that one advantage of the part-based pathway is the ability to generalize across domains, whereas the image-based pathway provides faster and more effortless recognition. PMID:19460948

Modular verification of chemical reaction network encodings via serializability analysis

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Lakin, Matthew R.; Stefanovic, Darko; Phillips, Andrew

2015-01-01

Chemical reaction networks are a powerful means of specifying the intended behaviour of synthetic biochemical systems. A high-level formal specification, expressed as a chemical reaction network, may be compiled into a lower-level encoding, which can be directly implemented in wet chemistry and may itself be expressed as a chemical reaction network. Here we present conditions under which a lower-level encoding correctly emulates the sequential dynamics of a high-level chemical reaction network. We require that encodings are transactional, such that their execution is divided by a “commit reaction” that irreversibly separates the reactant-consuming phase of the encoding from the product-generating phase. We also impose restrictions on the sharing of species between reaction encodings, based on a notion of “extra tolerance”, which defines species that may be shared between encodings without enabling unwanted reactions. Our notion of correctness is serializability of interleaved reaction encodings, and if all reaction encodings satisfy our correctness properties then we can infer that the global dynamics of the system are correct. This allows us to infer correctness of any system constructed using verified encodings. As an example, we show how this approach may be used to verify two- and four-domain DNA strand displacement encodings of chemical reaction networks, and we generalize our result to the limit where the populations of helper species are unlimited. PMID:27325906

High-Efficient Parallel CAVLC Encoders on Heterogeneous Multicore Architectures

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H. Y. Su

2012-04-01

Full Text Available This article presents two high-efficient parallel realizations of the context-based adaptive variable length coding (CAVLC based on heterogeneous multicore processors. By optimizing the architecture of the CAVLC encoder, three kinds of dependences are eliminated or weaken, including the context-based data dependence, the memory accessing dependence and the control dependence. The CAVLC pipeline is divided into three stages: two scans, coding, and lag packing, and be implemented on two typical heterogeneous multicore architectures. One is a block-based SIMD parallel CAVLC encoder on multicore stream processor STORM. The other is a component-oriented SIMT parallel encoder on massively parallel architecture GPU. Both of them exploited rich data-level parallelism. Experiments results show that compared with the CPU version, more than 70 times of speedup can be obtained for STORM and over 50 times for GPU. The implementation of encoder on STORM can make a real-time processing for 1080p @30fps and GPU-based version can satisfy the requirements for 720p real-time encoding. The throughput of the presented CAVLC encoders is more than 10 times higher than that of published software encoders on DSP and multicore platforms.

Indirect Encoding in Neuroevolutionary Ship Handling

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Miroslaw Lacki

2018-03-01

Full Text Available In this paper the author compares the efficiency of two encoding schemes for artificial intelligence methods used in the neuroevolutionary ship maneuvering system. This may be also be seen as the ship handling system that simulates a learning process of a group of artificial helmsmen - autonomous control units, created with an artificial neural network. The helmsman observes input signals derived form an enfironment and calculates the values of required parameters of the vessel maneuvering in confined waters. In neuroevolution such units are treated as individuals in population of artificial neural networks, which through environmental sensing and evolutionary algorithms learn to perform given task efficiently. The main task of this project is to evolve a population of helmsmen with indirect encoding and compare results of simulation with direct encoding method.

What is a "good" encoding of guarded choice?

DEFF Research Database (Denmark)

Nestmann, Uwe

2000-01-01

into the latter that preserves divergence-freedom and symmetries. This paper argues that there are nevertheless "good" encodings between these calculi. In detail, we present a series of encodings for languages with (1) input-guarded choice, (2) both input and output-guarded choice, and (3) mixed-guarded choice......, and investigate them with respect to compositionality and divergence-freedom. The first and second encoding satisfy all of the above criteria, but various "good" candidates for the third encoding-inspired by an existing distributed implementation-invalidate one or the other criterion, While essentially confirming...... Palamidessi's result, our study suggests that the combination of strong compositionality and divergence-freedom is too strong for more practical purposes. (C) 2000 Academic Press....

Encoding specificity manipulations do affect retrieval from memory.

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Zeelenberg, René

2005-05-01

In a recent article, P.A. Higham (2002) [Strong cues are not necessarily weak: Thomson and Tulving (1970) and the encoding specificity principle revisited. Memory &Cognition, 30, 67-80] proposed a new way to analyze cued recall performance in terms of three separable aspects of memory (retrieval, monitoring, and report bias) by comparing performance under both free-report and forced-report instructions. He used this method to derive estimates of these aspects of memory in an encoding specificity experiment similar to that reported by D.M. Thomson and E. Tulving (1970) [Associative encoding and retrieval: weak and strong cues. Journal of Experimental Psychology, 86, 255-262]. Under forced-report instructions, the encoding specificity manipulation did not affect performance. Higham concluded that the manipulation affected monitoring and report bias, but not retrieval. I argue that this interpretation of the results is problematic because the Thomson and Tulving paradigm is confounded, and show in three experiments using a more appropriate design that encoding specificity manipulations do affect performance in forced-report cued recall. Because in Higham's framework forced-report performance provides a measure of retrieval that is uncontaminated by monitoring and report bias it is concluded that encoding specificity manipulations do affect retrieval from memory.

Encoding of electrophysiology and other signals in MR images

DEFF Research Database (Denmark)

Hanson, Lars G; Lund, Torben E; Hanson, Christian G

2007-01-01

to the "magstripe" technique used for encoding of soundtracks in motion pictures, the electrical signals are in this way encoded as artifacts appearing in the MR images or spectra outside the region of interest. The encoded signals are subsequently reconstructed from the signal recorded by the scanner. RESULTS...

Beyond Initial Encoding: Measures of the Post-Encoding Status of Memory Traces Predict Long-Term Recall during Infancy

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Pathman, Thanujeni; Bauer, Patricia J.

2013-01-01

The first years of life are witness to rapid changes in long-term recall ability. In the current research we contributed to an explanation of the changes by testing the absolute and relative contributions to long-term recall of encoding and post-encoding processes. Using elicited imitation, we sampled the status of 16-, 20-, and 24-month-old…

Incremental phonological encoding during unscripted sentence production

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Florian T Jaeger

2012-11-01

Full Text Available We investigate phonological encoding during unscripted sentence production, focusing on the effect of phonological overlap on phonological encoding. Previous work on this question has almost exclusively employed isolated word production or highly scripted multiword production. These studies have led to conflicting results: some studies found that phonological overlap between two words facilitates phonological encoding, while others found inhibitory effects. One worry with many of these paradigms is that they involve processes that are not typical to everyday language use, which calls into question to what extent their findings speak to the architectures and mechanisms underlying language production. We present a paradigm to investigate the consequences of phonological overlap between words in a sentence while leaving speakers much of the lexical and structural choices typical in everyday language use. Adult native speakers of English described events in short video clips. We annotated the presence of disfluencies and the speech rate at various points throughout the sentence, as well as the constituent order. We find that phonological overlap has an inhibitory effect on phonological encoding. Specifically, if adjacent content words share their phonological onset (e.g., hand the hammer, they are preceded by production difficulty, as reflected in fluency and speech rate. We also find that this production difficulty affects speakers’ constituent order preferences during grammatical encoding. We discuss our results and previous works to isolate the properties of other paradigms that resulted in facilitatory or inhibitory results. The data from our paradigm also speak to questions about the scope of phonological planning in unscripted speech and as to whether phonological and grammatical encoding interact.

Virally encoded 7TM receptors

DEFF Research Database (Denmark)

Rosenkilde, M M; Waldhoer, M; Lüttichau, H R

2001-01-01

expression of this single gene in certain lymphocyte cell lineages leads to the development of lesions which are remarkably similar to Kaposi's sarcoma, a human herpesvirus 8 associated disease. Thus, this and other virally encoded 7TM receptors appear to be attractive future drug targets.......A number of herpes- and poxviruses encode 7TM G-protein coupled receptors most of which clearly are derived from their host chemokine system as well as induce high expression of certain 7TM receptors in the infected cells. The receptors appear to be exploited by the virus for either immune evasion...

Improved entropy encoding for high efficient video coding standard

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B.S. Sunil Kumar

2018-03-01

Full Text Available The High Efficiency Video Coding (HEVC has better coding efficiency, but the encoding performance has to be improved to meet the growing multimedia applications. This paper improves the standard entropy encoding by introducing the optimized weighing parameters, so that higher rate of compression can be accomplished over the standard entropy encoding. The optimization is performed using the recently introduced firefly algorithm. The experimentation is carried out using eight benchmark video sequences and the PSNR for varying rate of data transmission is investigated. Comparative analysis based on the performance statistics is made with the standard entropy encoding. From the obtained results, it is clear that the originality of the decoded video sequence is preserved far better than the proposed method, though the compression rate is increased. Keywords: Entropy, Encoding, HEVC, PSNR, Compression

Accelerated radial Fourier-velocity encoding using compressed sensing

Energy Technology Data Exchange (ETDEWEB)

Hilbert, Fabian; Han, Dietbert [Wuerzburg Univ. (Germany). Inst. of Radiology; Wech, Tobias; Koestler, Herbert [Wuerzburg Univ. (Germany). Inst. of Radiology; Wuerzburg Univ. (Germany). Comprehensive Heart Failure Center (CHFC)

2014-10-01

Purpose:Phase Contrast Magnetic Resonance Imaging (MRI) is a tool for non-invasive determination of flow velocities inside blood vessels. Because Phase Contrast MRI only measures a single mean velocity per voxel, it is only applicable to vessels significantly larger than the voxel size. In contrast, Fourier Velocity Encoding measures the entire velocity distribution inside a voxel, but requires a much longer acquisition time. For accurate diagnosis of stenosis in vessels on the scale of spatial resolution, it is important to know the velocity distribution of a voxel. Our aim was to determine velocity distributions with accelerated Fourier Velocity Encoding in an acquisition time required for a conventional Phase Contrast image. Materials and Methods:We imaged the femoral artery of healthy volunteers with ECG - triggered, radial CINE acquisition. Data acquisition was accelerated by undersampling, while missing data were reconstructed by Compressed Sensing. Velocity spectra of the vessel were evaluated by high resolution Phase Contrast images and compared to spectra from fully sampled and undersampled Fourier Velocity Encoding. By means of undersampling, it was possible to reduce the scan time for Fourier Velocity Encoding to the duration required for a conventional Phase Contrast image. Results:Acquisition time for a fully sampled data set with 12 different Velocity Encodings was 40 min. By applying a 12.6 - fold retrospective undersampling, a data set was generated equal to 3:10 min acquisition time, which is similar to a conventional Phase Contrast measurement. Velocity spectra from fully sampled and undersampled Fourier Velocity Encoded images are in good agreement and show the same maximum velocities as compared to velocity maps from Phase Contrast measurements. Conclusion: Compressed Sensing proved to reliably reconstruct Fourier Velocity Encoded data. Our results indicate that Fourier Velocity Encoding allows an accurate determination of the velocity

Accelerated radial Fourier-velocity encoding using compressed sensing

International Nuclear Information System (INIS)

Hilbert, Fabian; Han, Dietbert

2014-01-01

Purpose:Phase Contrast Magnetic Resonance Imaging (MRI) is a tool for non-invasive determination of flow velocities inside blood vessels. Because Phase Contrast MRI only measures a single mean velocity per voxel, it is only applicable to vessels significantly larger than the voxel size. In contrast, Fourier Velocity Encoding measures the entire velocity distribution inside a voxel, but requires a much longer acquisition time. For accurate diagnosis of stenosis in vessels on the scale of spatial resolution, it is important to know the velocity distribution of a voxel. Our aim was to determine velocity distributions with accelerated Fourier Velocity Encoding in an acquisition time required for a conventional Phase Contrast image. Materials and Methods:We imaged the femoral artery of healthy volunteers with ECG - triggered, radial CINE acquisition. Data acquisition was accelerated by undersampling, while missing data were reconstructed by Compressed Sensing. Velocity spectra of the vessel were evaluated by high resolution Phase Contrast images and compared to spectra from fully sampled and undersampled Fourier Velocity Encoding. By means of undersampling, it was possible to reduce the scan time for Fourier Velocity Encoding to the duration required for a conventional Phase Contrast image. Results:Acquisition time for a fully sampled data set with 12 different Velocity Encodings was 40 min. By applying a 12.6 - fold retrospective undersampling, a data set was generated equal to 3:10 min acquisition time, which is similar to a conventional Phase Contrast measurement. Velocity spectra from fully sampled and undersampled Fourier Velocity Encoded images are in good agreement and show the same maximum velocities as compared to velocity maps from Phase Contrast measurements. Conclusion: Compressed Sensing proved to reliably reconstruct Fourier Velocity Encoded data. Our results indicate that Fourier Velocity Encoding allows an accurate determination of the velocity

Accelerated radial Fourier-velocity encoding using compressed sensing.

Science.gov (United States)

Hilbert, Fabian; Wech, Tobias; Hahn, Dietbert; Köstler, Herbert

2014-09-01

Phase Contrast Magnetic Resonance Imaging (MRI) is a tool for non-invasive determination of flow velocities inside blood vessels. Because Phase Contrast MRI only measures a single mean velocity per voxel, it is only applicable to vessels significantly larger than the voxel size. In contrast, Fourier Velocity Encoding measures the entire velocity distribution inside a voxel, but requires a much longer acquisition time. For accurate diagnosis of stenosis in vessels on the scale of spatial resolution, it is important to know the velocity distribution of a voxel. Our aim was to determine velocity distributions with accelerated Fourier Velocity Encoding in an acquisition time required for a conventional Phase Contrast image. We imaged the femoral artery of healthy volunteers with ECG-triggered, radial CINE acquisition. Data acquisition was accelerated by undersampling, while missing data were reconstructed by Compressed Sensing. Velocity spectra of the vessel were evaluated by high resolution Phase Contrast images and compared to spectra from fully sampled and undersampled Fourier Velocity Encoding. By means of undersampling, it was possible to reduce the scan time for Fourier Velocity Encoding to the duration required for a conventional Phase Contrast image. Acquisition time for a fully sampled data set with 12 different Velocity Encodings was 40 min. By applying a 12.6-fold retrospective undersampling, a data set was generated equal to 3:10 min acquisition time, which is similar to a conventional Phase Contrast measurement. Velocity spectra from fully sampled and undersampled Fourier Velocity Encoded images are in good agreement and show the same maximum velocities as compared to velocity maps from Phase Contrast measurements. Compressed Sensing proved to reliably reconstruct Fourier Velocity Encoded data. Our results indicate that Fourier Velocity Encoding allows an accurate determination of the velocity distribution in vessels in the order of the voxel size. Thus

Multiple-stage pure phase encoding with biometric information

Science.gov (United States)

Chen, Wen

2018-01-01

In recent years, many optical systems have been developed for securing information, and optical encryption/encoding has attracted more and more attention due to the marked advantages, such as parallel processing and multiple-dimensional characteristics. In this paper, an optical security method is presented based on pure phase encoding with biometric information. Biometric information (such as fingerprint) is employed as security keys rather than plaintext used in conventional optical security systems, and multiple-stage phase-encoding-based optical systems are designed for generating several phase-only masks with biometric information. Subsequently, the extracted phase-only masks are further used in an optical setup for encoding an input image (i.e., plaintext). Numerical simulations are conducted to illustrate the validity, and the results demonstrate that high flexibility and high security can be achieved.

MicroRNA-encoding long non-coding RNAs

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Zhu Xiaopeng

2008-05-01

Full Text Available Abstract Background Recent analysis of the mouse transcriptional data has revealed the existence of ~34,000 messenger-like non-coding RNAs (ml-ncRNAs. Whereas the functional properties of these ml-ncRNAs are beginning to be unravelled, no functional information is available for the large majority of these transcripts. Results A few ml-ncRNA have been shown to have genomic loci that overlap with microRNA loci, leading us to suspect that a fraction of ml-ncRNA may encode microRNAs. We therefore developed an algorithm (PriMir for specifically detecting potential microRNA-encoding transcripts in the entire set of 34,030 mouse full-length ml-ncRNAs. In combination with mouse-rat sequence conservation, this algorithm detected 97 (80 of them were novel strong miRNA-encoding candidates, and for 52 of these we obtained experimental evidence for the existence of their corresponding mature microRNA by microarray and stem-loop RT-PCR. Sequence analysis of the microRNA-encoding RNAs revealed an internal motif, whose presence correlates strongly (R2 = 0.9, P-value = 2.2 × 10-16 with the occurrence of stem-loops with characteristics of known pre-miRNAs, indicating the presence of a larger number microRNA-encoding RNAs (from 300 up to 800 in the ml-ncRNAs population. Conclusion Our work highlights a unique group of ml-ncRNAs and offers clues to their functions.

Graph Regularized Auto-Encoders for Image Representation.

Science.gov (United States)

Yiyi Liao; Yue Wang; Yong Liu

2017-06-01

Image representation has been intensively explored in the domain of computer vision for its significant influence on the relative tasks such as image clustering and classification. It is valuable to learn a low-dimensional representation of an image which preserves its inherent information from the original image space. At the perspective of manifold learning, this is implemented with the local invariant idea to capture the intrinsic low-dimensional manifold embedded in the high-dimensional input space. Inspired by the recent successes of deep architectures, we propose a local invariant deep nonlinear mapping algorithm, called graph regularized auto-encoder (GAE). With the graph regularization, the proposed method preserves the local connectivity from the original image space to the representation space, while the stacked auto-encoders provide explicit encoding model for fast inference and powerful expressive capacity for complex modeling. Theoretical analysis shows that the graph regularizer penalizes the weighted Frobenius norm of the Jacobian matrix of the encoder mapping, where the weight matrix captures the local property in the input space. Furthermore, the underlying effects on the hidden representation space are revealed, providing insightful explanation to the advantage of the proposed method. Finally, the experimental results on both clustering and classification tasks demonstrate the effectiveness of our GAE as well as the correctness of the proposed theoretical analysis, and it also suggests that GAE is a superior solution to the current deep representation learning techniques comparing with variant auto-encoders and existing local invariant methods.

Quantum Logical Operations on Encoded Qubits

International Nuclear Information System (INIS)

Zurek, W.H.; Laflamme, R.

1996-01-01

We show how to carry out quantum logical operations (controlled-not and Toffoli gates) on encoded qubits for several encodings which protect against various 1-bit errors. This improves the reliability of these operations by allowing one to correct for 1-bit errors which either preexisted or occurred in the course of operation. The logical operations we consider allow one to carry out the vast majority of the steps in the quantum factoring algorithm. copyright 1996 The American Physical Society

Nucleotide sequences of two genomic DNAs encoding peroxidase of Arabidopsis thaliana.

Science.gov (United States)

Intapruk, C; Higashimura, N; Yamamoto, K; Okada, N; Shinmyo, A; Takano, M

1991-02-15

The peroxidase (EC 1.11.1.7)-encoding gene of Arabidopsis thaliana was screened from a genomic library using a cDNA encoding a neutral isozyme of horseradish, Armoracia rusticana, peroxidase (HRP) as a probe, and two positive clones were isolated. From the comparison with the sequences of the HRP-encoding genes, we concluded that two clones contained peroxidase-encoding genes, and they were named prxCa and prxEa. Both genes consisted of four exons and three introns; the introns had consensus nucleotides, GT and AG, at the 5' and 3' ends, respectively. The lengths of each putative exon of the prxEa gene were the same as those of the HRP-basic-isozyme-encoding gene, prxC3, and coded for 349 amino acids (aa) with a sequence homology of 89% to that encoded by prxC3. The prxCa gene was very close to the HRP-neutral-isozyme-encoding gene, prxC1b, and coded for 354 aa with 91% homology to that encoded by prxC1b. The aa sequence homology was 64% between the two peroxidases encoded by prxCa and prxEa.

Thought probes during prospective memory encoding: Evidence for perfunctory processes

Science.gov (United States)

McDaniel, Mark A.; Dasse, Michelle N.; Lee, Ji hae; Kurinec, Courtney A.; Tami, Claudina; Krueger, Madison L.

2018-01-01

For nearly 50 years, psychologists have studied prospective memory, or the ability to execute delayed intentions. Yet, there remains a gap in understanding as to whether initial encoding of the intention must be elaborative and strategic, or whether some components of successful encoding can occur in a perfunctory, transient manner. In eight studies (N = 680), we instructed participants to remember to press the Q key if they saw words representing fruits (cue) during an ongoing lexical decision task. They then typed what they were thinking and responded whether they encoded fruits as a general category, as specific exemplars, or hardly thought about it at all. Consistent with the perfunctory view, participants often reported mind wandering (42.9%) and hardly thinking about the prospective memory task (22.5%). Even though participants were given a general category cue, many participants generated specific category exemplars (34.5%). Bayesian analyses of encoding durations indicated that specific exemplars came to mind in a perfunctory manner rather than via strategic, elaborative mechanisms. Few participants correctly guessed the research hypotheses and changing from fruit category cues to initial-letter cues eliminated reports of specific exemplar generation, thereby arguing against demand characteristics in the thought probe procedure. In a final experiment, encoding duration was unrelated to prospective memory performance; however, specific-exemplar encoders outperformed general-category encoders with no ongoing task monitoring costs. Our findings reveal substantial variability in intention encoding, and demonstrate that some components of prospective memory encoding can be done “in passing.” PMID:29874277

Impact of a Computer System and the Encoding Staff Organization on the Encoding Stays and on Health Institution Financial Production in France.

Science.gov (United States)

Sarazin, Marianne; El Merini, Amine; Staccini, Pascal

2016-01-01

In France, medicalization of information systems program (PMSI) is an essential tool for the management planning and funding of health. The performance of encoding data inherent to hospital stays has become a major challenge for health institutions. Some studies have highlighted the impact of organizations set up on encoding quality and financial production. The aim of this study is to evaluate a computerized information system and new staff organization impact for treatment of the encoded information.

Color Image Authentication and Recovery via Adaptive Encoding

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Chun-Hung Chen

2014-01-01

Full Text Available We describe an authentication and recovery scheme for color image protection based on adaptive encoding. The image blocks are categorized based on their contents and different encoding schemes are applied according to their types. Such adaptive encoding results in better image quality and more robust image authentication. The approximations of the luminance and chromatic channels are carefully calculated, and for the purpose of reducing the data size, differential coding is used to encode the channels with variable size according to the characteristic of the block. The recovery data which represents the approximation and the detail of the image is embedded for data protection. The necessary data is well protected by using error correcting coding and duplication. The experimental results demonstrate that our technique is able to identify and localize image tampering, while preserving high quality for both watermarked and recovered images.

Theory of multisource crosstalk reduction by phase-encoded statics

KAUST Repository

Schuster, Gerard T.

2011-03-01

Formulas are derived that relate the strength of the crosstalk noise in supergather migration images to the variance of time, amplitude and polarity shifts in encoding functions. A supergather migration image is computed by migrating an encoded supergather, where the supergather is formed by stacking a large number of encoded shot gathers. Analysis reveals that for temporal source static shifts in each shot gather, the crosstalk noise is exponentially reduced with increasing variance of the static shift and the square of source frequency. This is not too surprising because larger time shifts lead to less correlation between traces in different shot gathers, and so should tend to reduce the crosstalk noise. Analysis also reveals that combining both polarity and time statics is a superior encoding strategy compared to using either polarity statics or time statics alone. Signal-to-noise (SNR) estimates show that for a standard migration image and for an image computed by migrating a phase-encoded supergather; here, G is the number of traces in a shot gather, I is the number of stacking iterations in the supergather and S is the number of encoded/blended shot gathers that comprise the supergather. If the supergather can be uniformly divided up into Q unique sub-supergathers, then the resulting SNR of the final image is, which means that we can enhance image quality but at the expense of Q times more cost. The importance of these formulas is that they provide a precise understanding between different phase encoding strategies and image quality. Finally, we show that iterative migration of phase-encoded supergathers is a special case of passive seismic interferometry. We suggest that the crosstalk noise formulas can be helpful in designing optimal strategies for passive seismic interferometry and efficient extraction of Green\\'s functions from simulated supergathers. © 2011 The Authors Geophysical Journal International © 2011 RAS.

Re-engaging with the past: recapitulation of encoding operations during retrieval

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Alexa eMorcom

2014-05-01

Full Text Available Recollection of events is accompanied by selective reactivation of cortical regions which responded to specific sensory and cognitive dimensions of the original events. This reactivation is thought to reflect the reinstatement of stored memory representations and therefore to reflect memory content, but it may also reveal processes which support both encoding and retrieval. The present study used event-related functional magnetic resonance imaging (fMRI to investigate whether regions selectively engaged in encoding face and scene context with studied words are also re-engaged when the context is later retrieved. As predicted, encoding face and scene context with visually presented words elicited activity in distinct, context-selective regions. Retrieval of face and scene context also re-engaged some of the regions which had shown successful encoding effects. However, this recapitulation of encoding activity did not show the same context selectivity observed at encoding. Successful retrieval of both face and scene context re-engaged regions which had been associated with encoding of the other type of context, as well as those associated with encoding the same type of context. This recapitulation may reflect retrieval attempts which are not context-selective, but use shared retrieval cues to re-engage encoding operations in service of recollection.

Wavelength-encoded OCDMA system using opto-VLSI processors.

Science.gov (United States)

Aljada, Muhsen; Alameh, Kamal

2007-07-01

We propose and experimentally demonstrate a 2.5 Gbits/sper user wavelength-encoded optical code-division multiple-access encoder-decoder structure based on opto-VLSI processing. Each encoder and decoder is constructed using a single 1D opto-very-large-scale-integrated (VLSI) processor in conjunction with a fiber Bragg grating (FBG) array of different Bragg wavelengths. The FBG array spectrally and temporally slices the broadband input pulse into several components and the opto-VLSI processor generates codewords using digital phase holograms. System performance is measured in terms of the autocorrelation and cross-correlation functions as well as the eye diagram.

Wavelength-encoded OCDMA system using opto-VLSI processors

Science.gov (United States)

Aljada, Muhsen; Alameh, Kamal

2007-07-01

We propose and experimentally demonstrate a 2.5 Gbits/sper user wavelength-encoded optical code-division multiple-access encoder-decoder structure based on opto-VLSI processing. Each encoder and decoder is constructed using a single 1D opto-very-large-scale-integrated (VLSI) processor in conjunction with a fiber Bragg grating (FBG) array of different Bragg wavelengths. The FBG array spectrally and temporally slices the broadband input pulse into several components and the opto-VLSI processor generates codewords using digital phase holograms. System performance is measured in terms of the autocorrelation and cross-correlation functions as well as the eye diagram.

The new INRIM rotating encoder angle comparator (REAC)

International Nuclear Information System (INIS)

Pisani, Marco; Astrua, Milena

2017-01-01

A novel angle comparator has been built and tested at INRIM. The device is based on a double air bearing structure embedding a continuously rotating encoder, which is read by two heads: one fixed to the base of the comparator and a second fixed to the upper moving part of the comparator. The phase measurement between the two heads’ signals is proportional to the relative angle suspended between them (and, therefore, the angle between the base and the upper, movable part of the comparator). The advantage of this solution is to reduce the encoder graduation errors and to cancel the cyclic errors due to the interpolation of the encoder lines. By using only two pairs of reading heads, we have achieved an intrinsic accuracy of  ±0.04″ (rectangular distribution) that can be reduced through self-calibration. The residual cyclic errors have shown to be less than 0.01″ peak-to-peak. The random fluctuations are less than 0.01″ rms on a 100 s time interval. A further advantage of the rotating encoder is the intrinsic knowledge of the absolute position without the need of a zeroing procedure. Construction details of the rotating encoder angle comparator (REAC), characterization tests, and examples of practical use are given. (paper)

Noise level and MPEG-2 encoder statistics

Science.gov (United States)

Lee, Jungwoo

1997-01-01

Most software in the movie and broadcasting industries are still in analog film or tape format, which typically contains random noise that originated from film, CCD camera, and tape recording. The performance of the MPEG-2 encoder may be significantly degraded by the noise. It is also affected by the scene type that includes spatial and temporal activity. The statistical property of noise originating from camera and tape player is analyzed and the models for the two types of noise are developed. The relationship between the noise, the scene type, and encoder statistics of a number of MPEG-2 parameters such as motion vector magnitude, prediction error, and quant scale are discussed. This analysis is intended to be a tool for designing robust MPEG encoding algorithms such as preprocessing and rate control.

The effect of encoding duration on implicit and explicit eyewitness memory.

Science.gov (United States)

Carol, Rolando N; Schreiber Compo, Nadja

2018-05-01

The present study investigated the effect of encoding duration on implicit and explicit eyewitness memory. Participants (N = 227) viewed a mock crime (brief, 15-s vs. long, 30-s vs. irrelevant/control) and were then tested with both implicit and explicit memory prompts or with explicit memory prompts only. Brief-encoding participants revealed more critical details implicitly than long-encoding or control participants. Further, the number and percentage of accurate details recalled explicitly were higher for long-encoding than for brief-encoding participants. Implicit testing prior to explicit recall-as compared to completing a filler task-was detrimental to free recall performance. Interestingly, brief-encoding participants were significantly more likely to remember critical details implicitly but not explicitly than long-encoding participants. This is the first study to investigate implicit eyewitness memory for a multimodal mock crime. Findings are theoretically consistent with prior research on cognition while expanding upon the extant eyewitness memory and investigative interviewing literature. Published by Elsevier Inc.

Universal Quantum Computing with Arbitrary Continuous-Variable Encoding.

Science.gov (United States)

Lau, Hoi-Kwan; Plenio, Martin B

2016-09-02

Implementing a qubit quantum computer in continuous-variable systems conventionally requires the engineering of specific interactions according to the encoding basis states. In this work, we present a unified formalism to conduct universal quantum computation with a fixed set of operations but arbitrary encoding. By storing a qubit in the parity of two or four qumodes, all computing processes can be implemented by basis state preparations, continuous-variable exponential-swap operations, and swap tests. Our formalism inherits the advantages that the quantum information is decoupled from collective noise, and logical qubits with different encodings can be brought to interact without decoding. We also propose a possible implementation of the required operations by using interactions that are available in a variety of continuous-variable systems. Our work separates the "hardware" problem of engineering quantum-computing-universal interactions, from the "software" problem of designing encodings for specific purposes. The development of quantum computer architecture could hence be simplified.

Encoding plaintext by Fourier transform hologram in double random phase encoding using fingerprint keys

Science.gov (United States)

Takeda, Masafumi; Nakano, Kazuya; Suzuki, Hiroyuki; Yamaguchi, Masahiro

2012-09-01

It has been shown that biometric information can be used as a cipher key for binary data encryption by applying double random phase encoding. In such methods, binary data are encoded in a bit pattern image, and the decrypted image becomes a plain image when the key is genuine; otherwise, decrypted images become random images. In some cases, images decrypted by imposters may not be fully random, such that the blurred bit pattern can be partially observed. In this paper, we propose a novel bit coding method based on a Fourier transform hologram, which makes images decrypted by imposters more random. Computer experiments confirm that the method increases the randomness of images decrypted by imposters while keeping the false rejection rate as low as in the conventional method.

Encoding plaintext by Fourier transform hologram in double random phase encoding using fingerprint keys

International Nuclear Information System (INIS)

Takeda, Masafumi; Nakano, Kazuya; Suzuki, Hiroyuki; Yamaguchi, Masahiro

2012-01-01

It has been shown that biometric information can be used as a cipher key for binary data encryption by applying double random phase encoding. In such methods, binary data are encoded in a bit pattern image, and the decrypted image becomes a plain image when the key is genuine; otherwise, decrypted images become random images. In some cases, images decrypted by imposters may not be fully random, such that the blurred bit pattern can be partially observed. In this paper, we propose a novel bit coding method based on a Fourier transform hologram, which makes images decrypted by imposters more random. Computer experiments confirm that the method increases the randomness of images decrypted by imposters while keeping the false rejection rate as low as in the conventional method. (paper)

Assessment of physicians' awareness and knowledge of familial hypercholesterolemia in Saudi Arabia: Is there a gap?

Science.gov (United States)

Batais, Mohammed Ali; Almigbal, Turky H; Bin Abdulhak, Aref A; Altaradi, Hani B; AlHabib, Khalid F

2017-01-01

The scarcity of familial hypercholesterolemia (FH) cases reported in Saudi Arabia might be indicative of a lack of awareness of this common genetic disease among physicians. To assess physicians' awareness, practice, and knowledge of FH in Saudi Arabia. This is a cross-sectional study conducted among physicians at four tertiary hospitals in Riyadh, Saudi Arabia between March 2016 and May 2016 using a self-administered questionnaire. A total of 294 physicians completed the survey (response rate 90.1%). Overall, 92.9% of the participants have poor knowledge of FH while only 7.1% have acceptable knowledge. The majority (68.7%) of physicians rated their familiarity with FH as average or above average, and these had higher mean knowledge scores than participants with self-reported below average familiarity (mean 3.4 versus 2.6) (P knowledge scores compared to those without FH patients in their care (3.5 versus 2.9) (P = 0.006). In addition, there were statistically significant differences between physicians' mean knowledge scores and their ages, levels of training, and years in practice. Moreover, a substantial deficit was identified in the awareness of various clinical algorithms to diagnose patients with FH, cascade screening, specialist lipid services, and the existence of statin alternatives, such as proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors. A substantial deficit was found in the awareness, knowledge, practice, and detection of FH among physicians in Saudi Arabia. Extensive educational programs are required to raise physician awareness and implement best practices; only then can the impact of these interventions on FH management and patient outcome be assessed.

Determining the binding affinity of therapeutic monoclonal antibodies towards their native unpurified antigens in human serum.

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Christine Bee

Full Text Available Monoclonal antibodies (mAbs are a growing segment of therapeutics, yet their in vitro characterization remains challenging. While it is essential that a therapeutic mAb recognizes the native, physiologically occurring epitope, the generation and selection of mAbs often rely on the use of purified recombinant versions of the antigen that may display non-native epitopes. Here, we present a method to measure both, the binding affinity of a therapeutic mAb towards its native unpurified antigen in human serum, and the antigen's endogenous concentration, by combining the kinetic exclusion assay and Biacore's calibration free concentration analysis. To illustrate the broad utility of our method, we studied a panel of mAbs raised against three disparate soluble antigens that are abundant in the serum of healthy donors: proprotein convertase subtilisin/kexin type 9 (PCSK9, progranulin (PGRN, and fatty acid binding protein (FABP4. We also determined the affinity of each mAb towards its purified recombinant antigen and assessed whether the interactions were pH-dependent. Of the six mAbs studied, three did not appear to discriminate between the serum and recombinant forms of the antigen; one mAb bound serum antigen with a higher affinity than recombinant antigen; and two mAbs displayed a different affinity for serum antigen that could be explained by a pH-dependent interaction. Our results highlight the importance of taking pH into account when measuring the affinities of mAbs towards their serum antigens, since the pH of serum samples becomes increasingly alkaline upon aerobic handling.

Peptide-based anti-PCSK9 vaccines - an approach for long-term LDLc management.

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Gergana Galabova

Full Text Available Low Density Lipoprotein (LDL hypercholesterolemia, and its associated cardiovascular diseases, are some of the leading causes of death worldwide. The ability of proprotein convertase subtilisin/kexin 9 (PCSK9 to modulate circulating LDL cholesterol (LDLc concentrations made it a very attractive target for LDLc management. To date, the most advanced approaches for PCSK9 inhibition are monoclonal antibody (mAb therapies. Although shown to lower LDLc significantly, mAbs face functional limitations because of their relatively short in vivo half-lives necessitating frequent administration. Here, we evaluated the long-term efficacy and safety of PCSK9-specific active vaccines in different preclinical models.PCSK9 peptide-based vaccines were successfully selected by our proprietary technology. To test their efficacy, wild-type (wt mice, Ldlr+/- mice, and rats were immunized with highly immunogenic vaccine candidates. Vaccines induced generation of high-affine PCSK9-specific antibodies in all species. Group mean total cholesterol (TC concentration was reduced by up to 30%, and LDLc up to 50% in treated animals. Moreover, the PCSK9 vaccine-induced humoral immune response persisted for up to one year in mice, and reduced cholesterol levels significantly throughout the study. Finally, the vaccines were well tolerated in all species tested.Peptide-based anti-PCSK9 vaccines induce the generation of antibodies that are persistent, high-affine, and functional for up to one year. They are powerful and safe tools for long-term LDLc management, and thus may represent a novel therapeutic approach for the prevention and/or treatment of LDL hypercholesterolemia-related cardiovascular diseases in humans.

Circulating PCSK9 is lowered acutely following surgery.

Science.gov (United States)

Druce, Irena; Abujrad, Hussein; Chaker, Seham; Meggison, Hilary; Hill, Andrew; Raymond, Angela; Mayne, Janice; Ooi, Teik Chye

2017-11-17

A decrease in serum low-density lipoprotein cholesterol (LDL-C) is well documented after acute stress. Plasma proprotein convertase subtilisin kexin 9 (PCSK9), which promotes degradation of low-density lipoprotein receptor (LDL-R) resulting in reduced plasma clearance of low-density lipoproteins (LDL) and an increase in serum LDL-C, would be predicted to decrease. Yet, a few studies have demonstrated an increase 1-8 days after acute stress. Our objective was to assess the earlier status of plasma PCSK9, within the first 24 hours of onset of stress. We measured serum lipids and plasma PCSK9 in 39 patients before and soon after an elective surgical procedure (abdominal aortic aneurysm (AAA) repair). We observed an early decrease in PCSK9 following surgery, as well as a decrease in total cholesterol (TC), LDL-C, high-density lipoprotein cholesterol (HDL-C), non-high-density lipoprotein cholesterol (non-HDL-C) and triglycerides (TG). Unlike other studies which showed an increase in PCSK9 after the onset of stress, our study detected a fall in PCSK9 following acute surgical stress. The observed difference is likely due to the earlier timing of PCSK9 measurement in our study. Further studies involving serial poststress measurements for several days are needed to determine whether PCSK9 behaves as an acute-phase reactant, whether it displays a biphasic response to acute stress, and whether changes in circulating PCSK9 are responsible for lipoprotein changes observed after surgical stress. (Clinical Trial Registration: ClinicalTrials.gov study ID NCT00493389). © 2017 Wiley Periodicals, Inc.

Mechanism of Folding and Activation of Subtilisin Kexin Isozyme-1 (SKI-1)/Site-1 Protease (S1P)*

Science.gov (United States)

da Palma, Joel Ramos; Cendron, Laura; Seidah, Nabil Georges; Pasquato, Antonella; Kunz, Stefan

2016-01-01

The proprotein convertase subtilisin kexin isozyme-1 (SKI-1)/site-1 protease (S1P) is implicated in lipid homeostasis, the unfolded protein response, and lysosome biogenesis. The protease is further hijacked by highly pathogenic emerging viruses for the processing of their envelope glycoproteins. Zymogen activation of SKI-1/S1P requires removal of an N-terminal prodomain, by a multistep process, generating the mature enzyme. Here, we uncover a modular structure of the human SKI-1/S1P prodomain and define its function in folding and activation. We provide evidence that the N-terminal AB fragment of the prodomain represents an autonomous structural and functional unit that is necessary and sufficient for folding and partial activation. In contrast, the C-terminal BC fragment lacks a defined structure but is crucial for autoprocessing and full catalytic activity. Phylogenetic analysis revealed that the sequence of the AB domain is highly conserved, whereas the BC fragment shows considerable variation and seems even absent in some species. Notably, SKI-1/S1P of arthropods, like the fruit fly Drosophila melanogaster, contains a shorter prodomain comprised of full-length AB and truncated BC regions. Swapping the prodomain fragments between fly and human resulted in a fully mature and active SKI-1/S1P chimera. Our study suggests that primordial SKI-1/S1P likely contained a simpler prodomain consisting of the highly conserved AB fragment that represents an independent folding unit. The BC region appears as a later evolutionary acquisition, possibly allowing more subtle fine-tuning of the maturation process. PMID:26645686

Sample-to-SNP kit: a reliable, easy and fast tool for the detection of HFE p.H63D and p.C282Y variations associated to hereditary hemochromatosis.

Science.gov (United States)

Nielsen, Peter B; Petersen, Maja S; Ystaas, Viviana; Andersen, Rolf V; Hansen, Karin M; Blaabjerg, Vibeke; Refstrup, Mette

2012-10-01

Classical hereditary hemochromatosis involves the HFE-gene and diagnostic analysis of the DNA variants HFE p.C282Y (c.845G>A; rs1800562) and HFE p.H63D (c.187C>G; rs1799945). The affected protein alters the iron homeostasis resulting in iron overload in various tissues. The aim of this study was to validate the TaqMan-based Sample-to-SNP protocol for the analysis of the HFE-p.C282Y and p.H63D variants with regard to accuracy, usefulness and reproducibility compared to an existing SNP protocol. The Sample-to-SNP protocol uses an approach where the DNA template is made accessible from a cell lysate followed by TaqMan analysis. Besides the HFE-SNPs other eight SNPs were used as well. These SNPs were: Coagulation factor II-gene F2 c.20210G>A, Coagulation factor V-gene F5 p.R506Q (c.1517G>A; rs121917732), Mitochondria SNP: mt7028 G>A, Mitochondria SNP: mt12308 A>G, Proprotein convertase subtilisin/kexin type 9-gene PCSK9 p.R46L (c.137G>T), Plutathione S-transferase pi 1-gene GSTP1 p.I105V (c313A>G; rs1695), LXR g.-171 A>G, ZNF202 g.-118 G>T. In conclusion the Sample-to-SNP kit proved to be an accurate, reliable, robust, easy to use and rapid TaqMan-based SNP detection protocol, which could be quickly implemented in a routine diagnostic or research facility. Copyright © 2012. Published by Elsevier B.V.

My Approach to the Patient With Familial Hypercholesterolemia

Science.gov (United States)

Safarova, Maya S.; Kullo, Iftikhar J.

2017-01-01

Familial hypercholesterolemia (FH), a relatively common Mendelian genetic disorder, is associated with a dramatically increased lifetime risk of premature atherosclerotic cardiovascular disease due to elevated plasma low-density lipoprotein cholesterol (LDL-C) levels. The diagnosis of FH is based on clinical presentation or genetic testing. Early identification of patients with FH is of great public health importance because preventive strategies can lower the absolute lifetime cardiovascular risk and screening can detect affected relatives. However, low awareness, detection, and control of FH pose hurdles in the prevention of FH-related cardiovascular events. Of the estimated 0.65 million to 1 million patients with FH in the United States, less than 10% carry a diagnosis of FH. Based on registry data, a substantial proportion of patients with FH are receiving no or inadequate lipid-lowering therapy. Statins remain the mainstay of treatment for patients with FH. Lipoprotein apheresis and newly approved lipid-lowering drugs are valuable adjuncts to statin therapy, particularly when the LDL-C–lowering response is suboptimal. Monoclonal antibodies targeting proprotein convertase subtilisin/kexin type 9 provide an additional approximately 60% lowering of LDL-C levels and are approved for use in patients with FH. For homozygous FH, 2 new drugs that work independent of the LDL receptor pathway are available: an apolipoprotein B antisense oligonucleotide (mipomersen) and a microsomal triglyceride transfer protein inhibitor (lomitapide). This review attempts to critically examine the available data to provide a summary of the current evidence for managing patients with FH, including screening, diagnosis, treatment, and surveillance. PMID:27261867

Critical role of bioanalytical strategies in investigation of clinical PK observations, a Phase I case study

Science.gov (United States)

Peng, Kun; Xu, Keyang; Liu, Luna; Hendricks, Robert; Delarosa, Reginald; Erickson, Rich; Budha, Nageshwar; Leabman, Maya; Song, An; Kaur, Surinder; Fischer, Saloumeh K

2014-01-01

RG7652 is a human immunoglobulin 1 (IgG1) monoclonal antibody (mAb) targeting proprotein convertase subtilisin/kexin type 9 (PCSK9) and is designed for the treatment of hypercholesterolemia. A target-binding enzyme-linked immunosorbent assay (ELISA) was developed to measure RG7652 levels in human serum in a Phase I study. Although target-binding assay formats are generally used to quantify free therapeutic, the actual therapeutic species being measured are affected by assay conditions, such as sample dilution and incubation time, and levels of soluble target in the samples. Therefore, in the presence of high concentrations of circulating target, the choice of reagents and assay conditions can have a significant effect on the observed pharmacokinetic (PK) profiles. Phase I RG7652 PK analysis using the ELISA data resulted in a nonlinear dose normalized exposure. An investigation was conducted to characterize the ELISA to determine whether the assay format and reagents may have contributed to the PK observation. In addition, to confirm the ELISA results, a second orthogonal method, liquid chromatography tandem mass spectrometry (LC-MS/MS) using a signature peptide as surrogate, was developed and implemented. A subset of PK samples, randomly selected from half of the subjects in the 6 single ascending dose (SAD) cohorts in the Phase I clinical study, was analyzed with the LC-MS/MS assay, and the data were found to be comparable to the ELISA data. This paper illustrates the importance of reagent characterization, as well as the benefits of using an orthogonal approach to eliminate bioanalytical contributions when encountering unexpected observations. PMID:25484037

Annexin A2 is a natural extrahepatic inhibitor of the PCSK9-induced LDL receptor degradation.

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Nabil G Seidah

Full Text Available Proprotein convertase subtilisin/kexin-9 (PCSK9 enhances the degradation of hepatic low-density lipoprotein receptor (LDLR. Deletion of PCSK9, and loss-of-function mutants in humans result in lower levels of circulating LDL-cholesterol and a strong protection against coronary heart disease. Accordingly, the quest for PCSK9 inhibitors has major clinical implications. We have previously identified annexin A2 (AnxA2 as an endogenous binding partner and functional inhibitor of PCSK9. Herein, we studied the relevance of AnxA2 in PCSK9 inhibition and lipid metabolism in vivo. Plasma analyses of AnxA2(-/- mice revealed: i a ∼1.4-fold increase in LDL-cholesterol without significant changes in VLDLs or HDLs, and ii a ∼2-fold increase in circulating PCSK9 levels. Western blotting and immunohistochemistry of AnxA2(-/- tissues revealed that the LDLR was decreased by ∼50% in extrahepatic tissues, such as adrenals and colon. We also show that AnxA2-derived synthetic peptides block the PCSK9≡LDLR interaction in vitro, and adenoviral overexpression of AnxA2 in mouse liver increases LDLR protein levels in vivo. These results suggest that AnxA2 acts as an endogenous regulator of LDLR degradation, mostly in extrahepatic tissues. Finally, we identified an AnxA2 coding polymorphism, V98L, that correlates with lower circulating levels of PCSK9 thereby extending our results on the physiological role of AnxA2 in humans.

O-Glycosylation Modulates Proprotein Convertase Activation of Angiopoietin-like Protein 3: POSSIBLE ROLE OF POLYPEPTIDE GalNAc-TRANSFERASE-2 IN REGULATION OF CONCENTRATIONS OF PLASMA LIPIDS

DEFF Research Database (Denmark)

Schjoldager, Katrine Ter-Borch Gram; Vester-Christensen, Malene B; Bennett, Eric Paul

2010-01-01

immediately C-terminal (TT(226)). We developed an in vivo model system in CHO ldlD cells that was used to show that O-glycosylation in the processing site blocked processing of ANGPTL3. Genome-wide SNP association studies have identified the polypeptide GalNAc-transferase gene, GALNT2, as a candidate gene...... for low HDL and high triglyceride blood levels. We hypothesized that the GalNAc-T2 transferase performed critical O-glycosylation of proteins involved in lipid metabolism. Screening of a panel of proteins known to affect lipid metabolism for potential sites glycosylated by GalNAc-T2 led to identification...

Encoded libraries of chemically modified peptides.

Science.gov (United States)

Heinis, Christian; Winter, Greg

2015-06-01

The use of powerful technologies for generating and screening DNA-encoded protein libraries has helped drive the development of proteins as pharmaceutical ligands. However the development of peptides as pharmaceutical ligands has been more limited. Although encoded peptide libraries are typically several orders of magnitude larger than classical chemical libraries, can be more readily screened, and can give rise to higher affinity ligands, their use as pharmaceutical ligands is limited by their intrinsic properties. Two of the intrinsic limitations include the rotational flexibility of the peptide backbone and the limited number (20) of natural amino acids. However these limitations can be overcome by use of chemical modification. For example, the libraries can be modified to introduce topological constraints such as cyclization linkers, or to introduce new chemical entities such as small molecule ligands, fluorophores and photo-switchable compounds. This article reviews the chemistry involved, the properties of the peptide ligands, and the new opportunities offered by chemical modification of DNA-encoded peptide libraries. Copyright © 2015. Published by Elsevier Ltd.

Performance study of large area encoding readout MRPC

Science.gov (United States)

Chen, X. L.; Wang, Y.; Chen, G.; Han, D.; Wang, X.; Zeng, M.; Zeng, Z.; Zhao, Z.; Guo, B.

2018-02-01

Muon tomography system built by the 2-D readout high spatial resolution Multi-gap Resistive Plate Chamber (MRPC) detector is a project of Tsinghua University. An encoding readout method based on the fine-fine configuration has been used to minimize the number of the readout electronic channels resulting in reducing the complexity and the cost of the system. In this paper, we provide a systematic comparison of the MRPC detector performance with and without fine-fine encoding readout. Our results suggest that the application of the fine-fine encoding readout leads us to achieve a detecting system with slightly worse spatial resolution but dramatically reduce the number of electronic channels.

Analysis of Program Obfuscation Schemes with Variable Encoding Technique

Science.gov (United States)

Fukushima, Kazuhide; Kiyomoto, Shinsaku; Tanaka, Toshiaki; Sakurai, Kouichi

Program analysis techniques have improved steadily over the past several decades, and software obfuscation schemes have come to be used in many commercial programs. A software obfuscation scheme transforms an original program or a binary file into an obfuscated program that is more complicated and difficult to analyze, while preserving its functionality. However, the security of obfuscation schemes has not been properly evaluated. In this paper, we analyze obfuscation schemes in order to clarify the advantages of our scheme, the XOR-encoding scheme. First, we more clearly define five types of attack models that we defined previously, and define quantitative resistance to these attacks. Then, we compare the security, functionality and efficiency of three obfuscation schemes with encoding variables: (1) Sato et al.'s scheme with linear transformation, (2) our previous scheme with affine transformation, and (3) the XOR-encoding scheme. We show that the XOR-encoding scheme is superior with regard to the following two points: (1) the XOR-encoding scheme is more secure against a data-dependency attack and a brute force attack than our previous scheme, and is as secure against an information-collecting attack and an inverse transformation attack as our previous scheme, (2) the XOR-encoding scheme does not restrict the calculable ranges of programs and the loss of efficiency is less than in our previous scheme.

Quantum control mechanism analysis through field based Hamiltonian encoding

International Nuclear Information System (INIS)

Mitra, Abhra; Rabitz, Herschel

2006-01-01

Optimal control of quantum dynamics in the laboratory is proving to be increasingly successful. The control fields can be complex, and the mechanisms by which they operate have often remained obscure. Hamiltonian encoding (HE) has been proposed as a method for understanding mechanisms in quantum dynamics. In this context mechanism is defined in terms of the dominant quantum pathways leading to the final state of the controlled system. HE operates by encoding a special modulation into the Hamiltonian and decoding its signature in the dynamics to determine the dominant pathway amplitudes. Earlier work encoded the modulation directly into the Hamiltonian operators. This present work introduces the alternative scheme of field based HE, where the modulation is encoded into the control field and not directly into the Hamiltonian operators. This distinct form of modulation yields a new perspective on mechanism and is computationally faster than the earlier approach. Field based encoding is also an important step towards a laboratory based algorithm for HE as it is the only form of encoding that may be experimentally executed. HE is also extended to cover systems with noise and uncertainty and finally, a hierarchical algorithm is introduced to reveal mechanism in a stepwise fashion of ever increasing detail as desired. This new hierarchical algorithm is an improvement over earlier approaches to HE where the entire mechanism was determined in one stroke. The improvement comes from the use of less complex modulation schemes, which leads to fewer evaluations of Schroedinger's equation. A number of simulations are presented on simple systems to illustrate the new field based encoding technique for mechanism assessment

Effect of tobacco craving cues on memory encoding and retrieval in smokers.

Science.gov (United States)

Heishman, Stephen J; Boas, Zachary P; Hager, Marguerite C; Taylor, Richard C; Singleton, Edward G; Moolchan, Eric T

2006-07-01

Previous studies have shown that cue-elicited tobacco craving disrupted performance on cognitive tasks; however, no study has examined directly the effect of cue-elicited craving on memory encoding and retrieval. A distinction between encoding and retireval has been reported such that memory is more impaired when attention is divided at encoding than at retrieval. This study tested the hypothesis that active imagery of smoking situations would impair encoding processes, but have little effect on retrieval. Imagery scripts (cigarette craving and neutral content) were presented either before presentation of a word list (encoding trials) or before word recall (retrieval trials). A working memory task at encoding and free recall of words were assessed. Results indicated that active imagery disrupted working memory on encoding trials, but not on retrieval trials. There was a trend toward impaired working memory following craving scripts compared with neutral scripts. These data support the hypothesis that the cognitive underpinnings of encoding and retrieval processes are distinct.

Emotion experienced during encoding enhances odor retrieval cue effectiveness.

Science.gov (United States)

Herz, R S

1997-01-01

Emotional potentiation may be a key variable in the formation of odor-associated memory. Two experiments were conducted in which a distinctive ambient odor was present or absent during encoding and retrieval sessions and subjects were in an anxious or neutral mood during encoding. Subjects' mood at retrieval was not manipulated. The laboratory mood induction used in Experiment 1 suggested that anxiety might increase the effectiveness of an odor retrieval cue. This trend was confirmed in Experiment 2 by capturing a naturally stressful situation. Subjects who had an ambient odor cue available and were in a preexam state during encoding recalled more words than subjects in any other group. These data are evidence that heightened emotion experienced during encoding with an ambient odor can enhance the effectiveness of an odor as a cue to memory.

Distinctiveness of Encoding and Memory for Learning Tasks.

Science.gov (United States)

Glover, John A.; And Others

1982-01-01

A distinctiveness of encoding hypothesis, as applied to the facilitative effects that higher order objectives have on readers' prose recall, was evaluated in three experiments. Results suggest that distinctiveness of encoding may offer a theoretical basis for the effects of adjunct aids as well as a guide to their construction. (Author/GK)

A hybrid bit-encoding for SAT planning based on clique-partitioning

Science.gov (United States)

Tapia, Cristóbal; San Segundo, Pablo; Galán, Ramón

2017-09-01

Planning as satisfiability is one of the most efficient ways to solve classic automated planning problems. In SAT planning, the encoding used to convert the problem to a SAT formula is critical for the performance of the SAT solver. This paper presents a novel bit-encoding that reduces the number of bits required to represent actions in a SAT-based automated planning problem. To obtain such encoding we first build a conflict graph, which represents incompatibilities of pairs of actions, and bitwise encode the subsets of actions determined by a clique partition. This reduces the number of Boolean variables and clauses of the SAT encoding, while preserving the possibility of parallel execution of compatible (non-neighbor) actions. The article also describes an appropriate algorithm for selecting the clique partition for this application and compares the new encodings obtained over some standard planning problems.

The herpesvirus 8-encoded chemokine vMIP-II, but not the poxvirus-encoded chemokine MC148, inhibits the CCR10 receptor

DEFF Research Database (Denmark)

Lüttichau, H R; Lewis, I C; Gerstoft, J

2001-01-01

The viral chemokine antagonist vMIP-II encoded by human herpesvirus 8 (HHV8) and MC148 encoded by the poxvirus - Molluscum contagiosum - were tested against the newly identified chemokine receptor CCR10. As the CCR10 ligand ESkine / CCL27 had the highest identity to MC148 and because both...

Quantum-dots-encoded-microbeads based molecularly imprinted polymer.

Science.gov (United States)

Liu, Yixi; Liu, Le; He, Yonghong; He, Qinghua; Ma, Hui

2016-03-15

Quantum dots encoded microbeads have various advantages such as large surface area, superb optical properties and the ability of multiplexing. Molecularly imprinted polymer that can mimic the natural recognition entities has high affinity and selectivity for the specific analyte. Here, the concept of utilizing the quantum dots encoded microbeads as the supporting material and the polydopamine as the functional monomer to form the core-shell molecular imprinted polymer was proposed for the first time. The resulted imprinted polymer can provide various merits: polymerization can complete in aqueous environment; fabrication procedure is facile and universal; the obvious economic advantage; the thickness of the imprinting layer is highly controllable; polydopamine coating can improve the biocompatibility of the quantum dot encoded microbeads. The rabbit IgG binding and flow cytometer experiment result showed the distinct advantages of this strategy: cost-saving, facile and fast preparation procedure. Most importantly, the ability for the multichannel detection, which makes the imprinted polydopamine modified encoded-beads very attractive in protein pre-concentration, recognition, separation and biosensing. Copyright © 2015 Elsevier B.V. All rights reserved.

Human factor H-related protein 2 (CFHR2 regulates complement activation.

Directory of Open Access Journals (Sweden)

Hannes U Eberhardt

Full Text Available Mutations and deletions within the human CFHR gene cluster on chromosome 1 are associated with diseases, such as dense deposit disease, CFHR nephropathy or age-related macular degeneration. Resulting mutant CFHR proteins can affect complement regulation. Here we identify human CFHR2 as a novel alternative pathway complement regulator that inhibits the C3 alternative pathway convertase and terminal pathway assembly. CFHR2 is composed of four short consensus repeat domains (SCRs. Two CFHR2 molecules form a dimer through their N-terminal SCRs, and each of the two C-terminal ends can bind C3b. C3b bound CFHR2 still allows C3 convertase formation but the CFHR2 bound convertases do not cleave the substrate C3. Interestingly CFHR2 hardly competes off factor H from C3b. Thus CFHR2 likely acts in concert with factor H, as CFHR2 inhibits convertases while simultaneously allowing factor H assisted degradation by factor I.

Human Transcriptome and Chromatin Modifications: An ENCODE Perspective

Directory of Open Access Journals (Sweden)

Li Shen

2013-06-01

Full Text Available A decade-long project, led by several international research groups, called the Encyclopedia of DNA Elements (ENCODE, recently released an unprecedented amount of data. The ambitious project covers transcriptome, cistrome, epigenome, and interactome data from more than 1,600 sets of experiments in human. To make use of this valuable resource, it is important to understand the information it represents and the techniques that were used to generate these data. In this review, we introduce the data that ENCODE generated, summarize the observations from the data analysis, and revisit a computational approach that ENCODE used to predict gene expression, with a focus on the human transcriptome and its association with chromatin modifications.

Enzymes and Enzyme Activity Encoded by Nonenveloped Viruses.

Science.gov (United States)

Azad, Kimi; Banerjee, Manidipa; Johnson, John E

2017-09-29

Viruses are obligate intracellular parasites that rely on host cell machineries for their replication and survival. Although viruses tend to make optimal use of the host cell protein repertoire, they need to encode essential enzymatic or effector functions that may not be available or accessible in the host cellular milieu. The enzymes encoded by nonenveloped viruses-a group of viruses that lack any lipid coating or envelope-play vital roles in all the stages of the viral life cycle. This review summarizes the structural, biochemical, and mechanistic information available for several classes of enzymes and autocatalytic activity encoded by nonenveloped viruses. Advances in research and development of antiviral inhibitors targeting specific viral enzymes are also highlighted.

Encoding efficiency of suprathreshold stochastic resonance on stimulus-specific information

Energy Technology Data Exchange (ETDEWEB)

Duan, Fabing, E-mail: fabing.duan@gmail.com [Institute of Complexity Science, Qingdao University, Qingdao 266071 (China); Chapeau-Blondeau, François, E-mail: chapeau@univ-angers.fr [Laboratoire Angevin de Recherche en Ingénierie des Systèmes (LARIS), Université d' Angers, 62 avenue Notre Dame du Lac, 49000 Angers (France); Abbott, Derek, E-mail: derek.abbott@adelaide.edu.au [Centre for Biomedical Engineering (CBME) and School of Electrical & Electronic Engineering, The University of Adelaide, Adelaide, SA 5005 (Australia)

2016-01-08

In this paper, we evaluate the encoding efficiency of suprathreshold stochastic resonance (SSR) based on a local information-theoretic measure of stimulus-specific information (SSI), which is the average specific information of responses associated with a particular stimulus. The theoretical and numerical analyses of SSIs reveal that noise can improve neuronal coding efficiency for a large population of neurons, which leads to produce increased information-rich responses. The SSI measure, in contrast to the global measure of average mutual information, can characterize the noise benefits in finer detail for describing the enhancement of neuronal encoding efficiency of a particular stimulus, which may be of general utility in the design and implementation of a SSR coding scheme. - Highlights: • Evaluating the noise-enhanced encoding efficiency via stimulus-specific information. • New form of stochastic resonance based on the measure of encoding efficiency. • Analyzing neural encoding schemes from suprathreshold stochastic resonance detailedly.

An Information Theoretic Characterisation of Auditory Encoding

Science.gov (United States)

Overath, Tobias; Cusack, Rhodri; Kumar, Sukhbinder; von Kriegstein, Katharina; Warren, Jason D; Grube, Manon; Carlyon, Robert P; Griffiths, Timothy D

2007-01-01

The entropy metric derived from information theory provides a means to quantify the amount of information transmitted in acoustic streams like speech or music. By systematically varying the entropy of pitch sequences, we sought brain areas where neural activity and energetic demands increase as a function of entropy. Such a relationship is predicted to occur in an efficient encoding mechanism that uses less computational resource when less information is present in the signal: we specifically tested the hypothesis that such a relationship is present in the planum temporale (PT). In two convergent functional MRI studies, we demonstrated this relationship in PT for encoding, while furthermore showing that a distributed fronto-parietal network for retrieval of acoustic information is independent of entropy. The results establish PT as an efficient neural engine that demands less computational resource to encode redundant signals than those with high information content. PMID:17958472

The effects of age on the neural correlates of episodic encoding.

Science.gov (United States)

Grady, C L; McIntosh, A R; Rajah, M N; Beig, S; Craik, F I

1999-12-01

Young and old adults underwent positron emission tomographic scans while encoding pictures of objects and words using three encoding strategies: deep processing (a semantic living/nonliving judgement), shallow processing (size judgement) and intentional learning. Picture memory exceeded word memory in both young and old groups, and there was an age-related decrement only in word recognition. During the encoding tasks three brain activity patterns were found that differentiated stimulus type and the different encoding strategies. The stimulus-specific pattern was characterized by greater activity in extrastriate and medial temporal cortices during picture encoding, and greater activity in left prefrontal and temporal cortices during encoding of words. The older adults showed this pattern to a significantly lesser degree. A pattern distinguishing deep processing from intentional learning of words and pictures was identified, characterized mainly by differences in prefrontal cortex, and this pattern also was of significantly lesser magnitude in the old group. A final pattern identified areas with increased activity during deep processing and intentional learning of pictures, including left prefrontal and bilateral medial temporal regions. There was no group difference in this pattern. These results indicate age-related dysfunction in several encoding networks, with sparing of one specifically involved in more elaborate encoding of pictures. These age-related changes appear to affect verbal memory more than picture memory.

Re-engaging with the past: recapitulation of encoding operations during episodic retrieval

Science.gov (United States)

Morcom, Alexa M.

2014-01-01

Recollection of events is accompanied by selective reactivation of cortical regions which responded to specific sensory and cognitive dimensions of the original events. This reactivation is thought to reflect the reinstatement of stored memory representations and therefore to reflect memory content, but it may also reveal processes which support both encoding and retrieval. The present study used event-related functional magnetic resonance imaging to investigate whether regions selectively engaged in encoding face and scene context with studied words are also re-engaged when the context is later retrieved. As predicted, encoding face and scene context with visually presented words elicited activity in distinct, context-selective regions. Retrieval of face and scene context also re-engaged some of the regions which had shown successful encoding effects. However, this recapitulation of encoding activity did not show the same context selectivity observed at encoding. Successful retrieval of both face and scene context re-engaged regions which had been associated with encoding of the other type of context, as well as those associated with encoding the same type of context. This recapitulation may reflect retrieval attempts which are not context-selective, but use shared retrieval cues to re-engage encoding operations in service of recollection. PMID:24904386

Encoding and Retrieval Interference in Sentence Comprehension: Evidence from Agreement

Directory of Open Access Journals (Sweden)

Sandra Villata

2018-01-01

Full Text Available Long-distance verb-argument dependencies generally require the integration of a fronted argument when the verb is encountered for sentence interpretation. Under a parsing model that handles long-distance dependencies through a cue-based retrieval mechanism, retrieval is hampered when retrieval cues also resonate with non-target elements (retrieval interference. However, similarity-based interference may also stem from interference arising during the encoding of elements in memory (encoding interference, an effect that is not directly accountable for by a cue-based retrieval mechanism. Although encoding and retrieval interference are clearly distinct at the theoretical level, it is difficult to disentangle the two on empirical grounds, since encoding interference may also manifest at the retrieval region. We report two self-paced reading experiments aimed at teasing apart the role of each component in gender and number subject-verb agreement in Italian and English object relative clauses. In Italian, the verb does not agree in gender with the subject, thus providing no cue for retrieval. In English, although present tense verbs agree in number with the subject, past tense verbs do not, allowing us to test the role of number as a retrieval cue within the same language. Results from both experiments converge, showing similarity-based interference at encoding, and some evidence for an effect at retrieval. After having pointed out the non-negligible role of encoding in sentence comprehension, and noting that Lewis and Vasishth’s (2005 ACT-R model of sentence processing, the most fully developed cue-based retrieval approach to sentence processing does not predict encoding effects, we propose an augmentation of this model that predicts these effects. We then also propose a self-organizing sentence processing model (SOSP, which has the advantage of accounting for retrieval and encoding interference with a single mechanism.

Encoding and Retrieval Interference in Sentence Comprehension: Evidence from Agreement

Science.gov (United States)

Villata, Sandra; Tabor, Whitney; Franck, Julie

2018-01-01

Long-distance verb-argument dependencies generally require the integration of a fronted argument when the verb is encountered for sentence interpretation. Under a parsing model that handles long-distance dependencies through a cue-based retrieval mechanism, retrieval is hampered when retrieval cues also resonate with non-target elements (retrieval interference). However, similarity-based interference may also stem from interference arising during the encoding of elements in memory (encoding interference), an effect that is not directly accountable for by a cue-based retrieval mechanism. Although encoding and retrieval interference are clearly distinct at the theoretical level, it is difficult to disentangle the two on empirical grounds, since encoding interference may also manifest at the retrieval region. We report two self-paced reading experiments aimed at teasing apart the role of each component in gender and number subject-verb agreement in Italian and English object relative clauses. In Italian, the verb does not agree in gender with the subject, thus providing no cue for retrieval. In English, although present tense verbs agree in number with the subject, past tense verbs do not, allowing us to test the role of number as a retrieval cue within the same language. Results from both experiments converge, showing similarity-based interference at encoding, and some evidence for an effect at retrieval. After having pointed out the non-negligible role of encoding in sentence comprehension, and noting that Lewis and Vasishth’s (2005) ACT-R model of sentence processing, the most fully developed cue-based retrieval approach to sentence processing does not predict encoding effects, we propose an augmentation of this model that predicts these effects. We then also propose a self-organizing sentence processing model (SOSP), which has the advantage of accounting for retrieval and encoding interference with a single mechanism. PMID:29403414

A SSVEP Stimuli Encoding Method Using Trinary Frequency-Shift Keying Encoded SSVEP (TFSK-SSVEP

Directory of Open Access Journals (Sweden)

Xing Zhao

2017-06-01

Full Text Available SSVEP is a kind of BCI technology with advantage of high information transfer rate. However, due to its nature, frequencies could be used as stimuli are scarce. To solve such problem, a stimuli encoding method which encodes SSVEP signal using Frequency Shift–Keying (FSK method is developed. In this method, each stimulus is controlled by a FSK signal which contains three different frequencies that represent “Bit 0,” “Bit 1” and “Bit 2” respectively. Different to common BFSK in digital communication, “Bit 0” and “Bit 1” composited the unique identifier of stimuli in binary bit stream form, while “Bit 2” indicates the ending of a stimuli encoding. EEG signal is acquired on channel Oz, O1, O2, Pz, P3, and P4, using ADS1299 at the sample rate of 250 SPS. Before original EEG signal is quadrature demodulated, it is detrended and then band-pass filtered using FFT-based FIR filtering to remove interference. Valid peak of the processed signal is acquired by calculating its derivative and converted into bit stream using window method. Theoretically, this coding method could implement at least 2n−1 (n is the length of bit command stimulus while keeping the ITR the same. This method is suitable to implement stimuli on a monitor and where the frequency and phase could be used to code stimuli is limited as well as implementing portable BCI devices which is not capable of performing complex calculations.

Noise and neuronal populations conspire to encode simple waveforms reliably

Science.gov (United States)

Parnas, B. R.

1996-01-01

Sensory systems rely on populations of neurons to encode information transduced at the periphery into meaningful patterns of neuronal population activity. This transduction occurs in the presence of intrinsic neuronal noise. This is fortunate. The presence of noise allows more reliable encoding of the temporal structure present in the stimulus than would be possible in a noise-free environment. Simulations with a parallel model of signal processing at the auditory periphery have been used to explore the effects of noise and a neuronal population on the encoding of signal information. The results show that, for a given set of neuronal modeling parameters and stimulus amplitude, there is an optimal amount of noise for stimulus encoding with maximum fidelity.

The effect of encoding strategy on the neural correlates of memory for faces.

Science.gov (United States)

Bernstein, Lori J; Beig, Sania; Siegenthaler, Amy L; Grady, Cheryl L

2002-01-01

Encoding and recognition of unfamiliar faces in young adults were examined using positron emission tomography to determine whether different encoding strategies would lead to encoding/retrieval differences in brain activity. Three types of encoding were compared: a 'deep' task (judging pleasantness/unpleasantness), a 'shallow' task (judging right/left orientation), and an intentional learning task in which subjects were instructed to learn the faces for a subsequent memory test but were not provided with a specific strategy. Memory for all faces was tested with an old/new recognition test. A modest behavioral effect was obtained, with deeply-encoded faces being recognized more accurately than shallowly-encoded or intentionally-learned faces. Regardless of encoding strategy, encoding activated a primarily ventral system including bilateral temporal and fusiform regions and left prefrontal cortices, whereas recognition activated a primarily dorsal set of regions including right prefrontal and parietal areas. Within encoding, the type of strategy produced different brain activity patterns, with deep encoding being characterized by left amygdala and left anterior cingulate activation. There was no effect of encoding strategy on brain activity during the recognition conditions. Posterior fusiform gyrus activation was related to better recognition accuracy in those conditions encouraging perceptual strategies, whereas activity in left frontal and temporal areas correlated with better performance during the 'deep' condition. Results highlight three important aspects of face memory: (1) the effect of encoding strategy was seen only at encoding and not at recognition; (2) left inferior prefrontal cortex was engaged during encoding of faces regardless of strategy; and (3) differential activity in fusiform gyrus was found, suggesting that activity in this area is not only a result of automatic face processing but is modulated by controlled processes.

Upconversion Nanoparticles-Encoded Hydrogel Microbeads-Based Multiplexed Protein Detection

Science.gov (United States)

Shikha, Swati; Zheng, Xiang; Zhang, Yong

2018-06-01

Fluorescently encoded microbeads are in demand for multiplexed applications in different fields. Compared to organic dye-based commercially available Luminex's xMAP technology, upconversion nanoparticles (UCNPs) are better alternatives due to their large anti-Stokes shift, photostability, nil background, and single wavelength excitation. Here, we developed a new multiplexed detection system using UCNPs for encoding poly(ethylene glycol) diacrylate (PEGDA) microbeads as well as for labeling reporter antibody. However, to prepare UCNPs-encoded microbeads, currently used swelling-based encapsulation leads to non-uniformity, which is undesirable for fluorescence-based multiplexing. Hence, we utilized droplet microfluidics to obtain encoded microbeads of uniform size, shape, and UCNPs distribution inside. Additionally, PEGDA microbeads lack functionality for probe antibodies conjugation on their surface. Methods to functionalize the surface of PEGDA microbeads (acrylic acid incorporation, polydopamine coating) reported thus far quench the fluorescence of UCNPs. Here, PEGDA microbeads surface was coated with silica followed by carboxyl modification without compromising the fluorescence intensity of UCNPs. In this study, droplet microfluidics-assisted UCNPs-encoded microbeads of uniform shape, size, and fluorescence were prepared. Multiple color codes were generated by mixing UCNPs emitting red and green colors at different ratios prior to encapsulation. UCNPs emitting blue color were used to label the reporter antibody. Probe antibodies were covalently immobilized on red UCNPs-encoded microbeads for specific capture of human serum albumin (HSA) as a model protein. The system was also demonstrated for multiplexed detection of both human C-reactive protein (hCRP) and HSA protein by immobilizing anti-hCRP antibodies on green UCNPs.

Latency Performance of Encoding with Random Linear Network Coding

DEFF Research Database (Denmark)

Nielsen, Lars; Hansen, René Rydhof; Lucani Rötter, Daniel Enrique

2018-01-01

the encoding process can be parallelized based on system requirements to reduce data access time within the system. Using a counting argument, we focus on predicting the effect of changes of generation (number of original packets) and symbol size (number of bytes per data packet) configurations on the encoding...... latency on full vector and on-the-fly algorithms. We show that the encoding latency doubles when either the generation size or the symbol size double and confirm this via extensive simulations. Although we show that the theoretical speed gain of on-the-fly over full vector is two, our measurements show...

On The Designed And Constructed Feedback Shift-Register Encoder

African Journals Online (AJOL)

An encoder capable of cyclical shifting of data, and which can therefore be used for Bose-Chaudhuri and Hocquenghem (BCH) coding, has been designed and constructed using discrete components. It comprises basically four bistable multivibrators and an exclusive-OR device. On completion, the encoder performed ...

ENCODE whole-genome data in the UCSC genome browser (2011 update).

Science.gov (United States)

Raney, Brian J; Cline, Melissa S; Rosenbloom, Kate R; Dreszer, Timothy R; Learned, Katrina; Barber, Galt P; Meyer, Laurence R; Sloan, Cricket A; Malladi, Venkat S; Roskin, Krishna M; Suh, Bernard B; Hinrichs, Angie S; Clawson, Hiram; Zweig, Ann S; Kirkup, Vanessa; Fujita, Pauline A; Rhead, Brooke; Smith, Kayla E; Pohl, Andy; Kuhn, Robert M; Karolchik, Donna; Haussler, David; Kent, W James

2011-01-01

The ENCODE project is an international consortium with a goal of cataloguing all the functional elements in the human genome. The ENCODE Data Coordination Center (DCC) at the University of California, Santa Cruz serves as the central repository for ENCODE data. In this role, the DCC offers a collection of high-throughput, genome-wide data generated with technologies such as ChIP-Seq, RNA-Seq, DNA digestion and others. This data helps illuminate transcription factor-binding sites, histone marks, chromatin accessibility, DNA methylation, RNA expression, RNA binding and other cell-state indicators. It includes sequences with quality scores, alignments, signals calculated from the alignments, and in most cases, element or peak calls calculated from the signal data. Each data set is available for visualization and download via the UCSC Genome Browser (http://genome.ucsc.edu/). ENCODE data can also be retrieved using a metadata system that captures the experimental parameters of each assay. The ENCODE web portal at UCSC (http://encodeproject.org/) provides information about the ENCODE data and links for access.

Dynamic Information Encoding With Dynamic Synapses in Neural Adaptation

Science.gov (United States)

Li, Luozheng; Mi, Yuanyuan; Zhang, Wenhao; Wang, Da-Hui; Wu, Si

2018-01-01

Adaptation refers to the general phenomenon that the neural system dynamically adjusts its response property according to the statistics of external inputs. In response to an invariant stimulation, neuronal firing rates first increase dramatically and then decrease gradually to a low level close to the background activity. This prompts a question: during the adaptation, how does the neural system encode the repeated stimulation with attenuated firing rates? It has been suggested that the neural system may employ a dynamical encoding strategy during the adaptation, the information of stimulus is mainly encoded by the strong independent spiking of neurons at the early stage of the adaptation; while the weak but synchronized activity of neurons encodes the stimulus information at the later stage of the adaptation. The previous study demonstrated that short-term facilitation (STF) of electrical synapses, which increases the synchronization between neurons, can provide a mechanism to realize dynamical encoding. In the present study, we further explore whether short-term plasticity (STP) of chemical synapses, an interaction form more common than electrical synapse in the cortex, can support dynamical encoding. We build a large-size network with chemical synapses between neurons. Notably, facilitation of chemical synapses only enhances pair-wise correlations between neurons mildly, but its effect on increasing synchronization of the network can be significant, and hence it can serve as a mechanism to convey the stimulus information. To read-out the stimulus information, we consider that a downstream neuron receives balanced excitatory and inhibitory inputs from the network, so that the downstream neuron only responds to synchronized firings of the network. Therefore, the response of the downstream neuron indicates the presence of the repeated stimulation. Overall, our study demonstrates that STP of chemical synapse can serve as a mechanism to realize dynamical neural

Least-squares reverse time migration of marine data with frequency-selection encoding

KAUST Repository

Dai, Wei; Huang, Yunsong; Schuster, Gerard T.

2013-01-01

The phase-encoding technique can sometimes increase the efficiency of the least-squares reverse time migration (LSRTM) by more than one order of magnitude. However, traditional random encoding functions require all the encoded shots to share

BANDWIDTH AND EFFICIENT ENCODING SCHEME COMBINING TCM-UGM TO STBC

OpenAIRE

ABDELMOUNAIM MOULAY LAKHDAR; MOHAMMED BELADGHAM; ABDESSELAM BASSOU,; MOHAMED BENAISSA

2011-01-01

In this paper, a bandwidth efficient encoding scheme is proposed. It combines the modified version of trellis coded-modulation (called trellis coded-modulation with Ungerboeck-Gray mapping, TCM-UGM) to space-time block code (STBC). The performance of this encoding scheme is investigated over memoryless Rayleigh fading (MRF) channel for throughput 2 bits/s/Hz. The simulation result, using 2/3 rate 16-state TCM-UGM encoder, two transmit antennas and two receive antennas, shows clearly that the ...

Encoding, training and retrieval in ferroelectric tunnel junctions

Science.gov (United States)

Xu, Hanni; Xia, Yidong; Xu, Bo; Yin, Jiang; Yuan, Guoliang; Liu, Zhiguo

2016-05-01

Ferroelectric tunnel junctions (FTJs) are quantum nanostructures that have great potential in the hardware basis for future neuromorphic applications. Among recently proposed possibilities, the artificial cognition has high hopes, where encoding, training, memory solidification and retrieval constitute a whole chain that is inseparable. However, it is yet envisioned but experimentally unconfirmed. The poor retention or short-term store of tunneling electroresistance, in particular the intermediate states, is still a key challenge in FTJs. Here we report the encoding, training and retrieval in BaTiO3 FTJs, emulating the key features of information processing in terms of cognitive neuroscience. This is implemented and exemplified through processing characters. Using training inputs that are validated by the evolution of both barrier profile and domain configuration, accurate recalling of encoded characters in the retrieval stage is demonstrated.

DNA-encoded chemical libraries - achievements and remaining challenges.

Science.gov (United States)

Favalli, Nicholas; Bassi, Gabriele; Scheuermann, Jörg; Neri, Dario

2018-04-23

DNA-encoded chemical libraries (DECLs) are collections of compounds, individually coupled to DNA tags serving as amplifiable identification barcodes. Since individual compounds can be identified by the associated DNA tag, they can be stored as a mixture, allowing the synthesis and screening of combinatorial libraries of unprecedented size, facilitated by the implementation of split-and-pool synthetic procedures or other experimental methodologies. In this review, we briefly present relevant concepts and technologies, which are required for the implementation and interpretation of screening procedures with DNA-encoded chemical libraries. Moreover, we illustrate some success stories, detailing how novel ligands were discovered from encoded libraries. Finally, we critically review what can realistically be achieved with the technology at the present time, highlighting challenges and opportunities for the future. © 2018 Federation of European Biochemical Societies.

The role of depth of encoding in attentional capture

NARCIS (Netherlands)

Sasin, Edyta; Nieuwenstein, Mark; Johnson, Addie

2015-01-01

The aim of the current study was to examine whether depth of encoding influences attentional capture by recently attended objects. In Experiment 1, participants first had to judge whether a word referred to a living or a nonliving thing (deep encoding condition) or whether the word was written in

Decoding and Encoding Facial Expressions in Preschool-Age Children.

Science.gov (United States)

Zuckerman, Miron; Przewuzman, Sylvia J.

1979-01-01

Preschool-age children drew, decoded, and encoded facial expressions depicting five different emotions. Accuracy of drawing, decoding and encoding each of the five emotions was consistent across the three tasks; decoding ability was correlated with drawing ability among female subjects, but neither of these abilities was correlated with encoding…

Optical encoder based on a nondiffractive beam

International Nuclear Information System (INIS)

Lutenberg, Ariel; Perez-Quintian, Fernando; Rebollo, Maria A.

2008-01-01

Optical encoders are used in industrial and laboratory motion equipment to measure rotations and linear displacements. We introduce a design of an optical encoder based on a nondiffractive beam. We expect that the invariant profile and radial symmetry of the nondiffractive beam provide the design with remarkable tolerance to mechanical perturbations. We experimentally demonstrate that the proposed design generates a suitable output sinusoidal signal with low harmonic distortion. Moreover, we present a numerical model of the system based on the angular spectrum approximation whose predictions are in excellent agreement with the experimental results

Dissociable effects of top-down and bottom-up attention during episodic encoding

Science.gov (United States)

Uncapher, Melina R.; Hutchinson, J. Benjamin; Wagner, Anthony D.

2011-01-01

It is well established that the formation of memories for life’s experiences—episodic memory—is influenced by how we attend to those experiences, yet the neural mechanisms by which attention shapes episodic encoding are still unclear. We investigated how top-down and bottom-up attention contribute to memory encoding of visual objects in humans by manipulating both types of attention during functional magnetic resonance imaging (fMRI) of episodic memory formation. We show that dorsal parietal cortex—specifically, intraparietal sulcus (IPS)—was engaged during top-down attention and was also recruited during the successful formation of episodic memories. By contrast, bottom-up attention engaged ventral parietal cortex—specifically, temporoparietal junction (TPJ)—and was also more active during encoding failure. Functional connectivity analyses revealed further dissociations in how top-down and bottom-up attention influenced encoding: while both IPS and TPJ influenced activity in perceptual cortices thought to represent the information being encoded (fusiform/lateral occipital cortex), they each exerted opposite effects on memory encoding. Specifically, during a preparatory period preceding stimulus presentation, a stronger drive from IPS was associated with a higher likelihood that the subsequently attended stimulus would be encoded. By contrast, during stimulus processing, stronger connectivity with TPJ was associated with a lower likelihood the stimulus would be successfully encoded. These findings suggest that during encoding of visual objects into episodic memory, top-down and bottom-up attention can have opposite influences on perceptual areas that subserve visual object representation, suggesting that one manner in which attention modulates memory is by altering the perceptual processing of to-be-encoded stimuli. PMID:21880922

Minimal-memory realization of pearl-necklace encoders of general quantum convolutional codes

International Nuclear Information System (INIS)

Houshmand, Monireh; Hosseini-Khayat, Saied

2011-01-01

Quantum convolutional codes, like their classical counterparts, promise to offer higher error correction performance than block codes of equivalent encoding complexity, and are expected to find important applications in reliable quantum communication where a continuous stream of qubits is transmitted. Grassl and Roetteler devised an algorithm to encode a quantum convolutional code with a ''pearl-necklace'' encoder. Despite their algorithm's theoretical significance as a neat way of representing quantum convolutional codes, it is not well suited to practical realization. In fact, there is no straightforward way to implement any given pearl-necklace structure. This paper closes the gap between theoretical representation and practical implementation. In our previous work, we presented an efficient algorithm to find a minimal-memory realization of a pearl-necklace encoder for Calderbank-Shor-Steane (CSS) convolutional codes. This work is an extension of our previous work and presents an algorithm for turning a pearl-necklace encoder for a general (non-CSS) quantum convolutional code into a realizable quantum convolutional encoder. We show that a minimal-memory realization depends on the commutativity relations between the gate strings in the pearl-necklace encoder. We find a realization by means of a weighted graph which details the noncommutative paths through the pearl necklace. The weight of the longest path in this graph is equal to the minimal amount of memory needed to implement the encoder. The algorithm has a polynomial-time complexity in the number of gate strings in the pearl-necklace encoder.

Dissociative effects of true and false recall as a function of different encoding strategies.

Science.gov (United States)

Goodwin, Kerri A

2007-01-01

Goodwin, Meissner, and Ericsson (2001) proposed a path model in which elaborative encoding predicted the likelihood of verbalisation of critical, nonpresented words at encoding, which in turn predicted the likelihood of false recall. The present study tested this model of false recall experimentally with a manipulation of encoding strategy and the implementation of the process-tracing technique of protocol analysis. Findings indicated that elaborative encoding led to more verbalisations of critical items during encoding than rote rehearsal of list items, but false recall rates were reduced under elaboration conditions (Experiment 2). Interestingly, false recall was more likely to occur when items were verbalised during encoding than not verbalised (Experiment 1), and participants tended to reinstate their encoding strategies during recall, particularly after elaborative encoding (Experiment 1). Theoretical implications for the interplay of encoding and retrieval processes of false recall are discussed.

Prefrontal activity and impaired memory encoding strategies in schizophrenia.

Science.gov (United States)

Guimond, Synthia; Hawco, Colin; Lepage, Martin

2017-08-01

Schizophrenia patients have significant memory difficulties that have far-reaching implications in their daily life. These impairments are partly attributed to an inability to self-initiate effective memory encoding strategies, but its core neurobiological correlates remain unknown. The current study addresses this critical gap in our knowledge of episodic memory impairments in schizophrenia. Schizophrenia patients (n = 35) and healthy controls (n = 23) underwent a Semantic Encoding Memory Task (SEMT) during an fMRI scan. Brain activity was examined for conditions where participants were a) prompted to use semantic encoding strategies, or b) not prompted but required to self-initiate such strategies. When prompted to use semantic encoding strategies, schizophrenia patients exhibited similar recognition performance and brain activity as healthy controls. However, when required to self-initiate these strategies, patients had significant reduced recognition performance and brain activity in the left dorsolateral prefrontal cortex, as well as in the left temporal gyrus, left superior parietal lobule, and cerebellum. When patients were divided based on performance on the SEMT, the subgroup with more severe deficits in self-initiation also showed greater reduction in left dorsolateral prefrontal activity. These results suggest that impaired self-initiation of elaborative encoding strategies is a driving feature of memory deficits in schizophrenia. We also identified the neural correlates of impaired self-initiation of semantic encoding strategies, in which a failure to activate the left dorsolateral prefrontal cortex plays a key role. These findings provide important new targets in the development of novel treatments aiming to improve memory and ultimately patients' outcome. Copyright © 2017. Published by Elsevier Ltd.

Least-squares reverse time migration of marine data with frequency-selection encoding

KAUST Repository

Dai, Wei

2013-06-24

The phase-encoding technique can sometimes increase the efficiency of the least-squares reverse time migration (LSRTM) by more than one order of magnitude. However, traditional random encoding functions require all the encoded shots to share the same receiver locations, thus limiting the usage to seismic surveys with a fixed spread geometry. We implement a frequency-selection encoding strategy that accommodates data with a marine streamer geometry. The encoding functions are delta functions in the frequency domain, so that all the encoded shots have unique nonoverlapping frequency content, and the receivers can distinguish the wavefield from each shot with a unique frequency band. Because the encoding functions are orthogonal to each other, there will be no crosstalk between different shots during modeling and migration. With the frequency-selection encoding method, the computational efficiency of LSRTM is increased so that its cost is comparable to conventional RTM for the Marmousi2 model and a marine data set recorded in the Gulf of Mexico. With more iterations, the LSRTM image quality is further improved by suppressing migration artifacts, balancing reflector amplitudes, and enhancing the spatial resolution. We conclude that LSRTM with frequency-selection is an efficient migration method that can sometimes produce more focused images than conventional RTM. © 2013 Society of Exploration Geophysicists.

Validation of a Real-time AVS Encoder on FPGA

Directory of Open Access Journals (Sweden)

Qun Fang Yuan

2014-01-01

Full Text Available A whole I frame AVS real-time video encoder is designed and implemented on FPGA platform in this paper. The system uses the structure of the flow calculation, coupled with a dual-port RAM memory between/among the various functional modules. Reusable design and pipeline design are used to optimize various encoding module and to ensure the efficient operation of the pipeline. Through the simulation of ISE software and the verification of Xilinx Vritex-4 pro platform, it can be seen that the highest working frequency can be up to 110 MHz, meeting the requirements of the whole I frame real- time encoding of AVS in CIF resolution.

A Neural Signature Encoding Decisions under Perceptual Ambiguity.

Science.gov (United States)

Sun, Sai; Yu, Rongjun; Wang, Shuo

2017-01-01

People often make perceptual decisions with ambiguous information, but it remains unclear whether the brain has a common neural substrate that encodes various forms of perceptual ambiguity. Here, we used three types of perceptually ambiguous stimuli as well as task instructions to examine the neural basis for both stimulus-driven and task-driven perceptual ambiguity. We identified a neural signature, the late positive potential (LPP), that encoded a general form of stimulus-driven perceptual ambiguity. In addition to stimulus-driven ambiguity, the LPP was also modulated by ambiguity in task instructions. To further specify the functional role of the LPP and elucidate the relationship between stimulus ambiguity, behavioral response, and the LPP, we employed regression models and found that the LPP was specifically associated with response latency and confidence rating, suggesting that the LPP encoded decisions under perceptual ambiguity. Finally, direct behavioral ratings of stimulus and task ambiguity confirmed our neurophysiological findings, which could not be attributed to differences in eye movements either. Together, our findings argue for a common neural signature that encodes decisions under perceptual ambiguity but is subject to the modulation of task ambiguity. Our results represent an essential first step toward a complete neural understanding of human perceptual decision making.

Encoding and decoding messages with chaotic lasers

International Nuclear Information System (INIS)

Alsing, P.M.; Gavrielides, A.; Kovanis, V.; Roy, R.; Thornburg, K.S. Jr.

1997-01-01

We investigate the structure of the strange attractor of a chaotic loss-modulated solid-state laser utilizing return maps based on a combination of intensity maxima and interspike intervals, as opposed to those utilizing Poincare sections defined by the intensity maxima of the laser (I=0,Ie<0) alone. We find both experimentally and numerically that a simple, intrinsic relationship exists between an intensity maximum and the pair of preceding and succeeding interspike intervals. In addition, we numerically investigate encoding messages on the output of a chaotic transmitter laser and its subsequent decoding by a similar receiver laser. By exploiting the relationship between the intensity maxima and the interspike intervals, we demonstrate that the method utilized to encode the message is vital to the system close-quote s ability to hide the signal from unwanted deciphering. In this work alternative methods are studied in order to encode messages by modulating the magnitude of pumping of the transmitter laser and also by driving its loss modulation with more than one frequency. copyright 1997 The American Physical Society

Encoding Effects on First-Graders' Use of Manipulatives

Science.gov (United States)

Osana, Helena P.; Przednowek, Katarzyna; Cooperman, Allyson; Adrien, Emmanuelle

2018-01-01

The effects of prior encodings of manipulatives (red and blue plastic chips) on children's ability to use them as representations of quantity were tested. First graders (N = 73) were assigned to four conditions in which the encoding of plastic chips was experimentally manipulated. All children then participated in an addition activity that relied…

On The Designed And Constructed Feedback Shift-Register Encoder

African Journals Online (AJOL)

Information transmission in noisy channels can be achieved with vanishingly small probability of error by proper coding of the information as long as the encoding rate is less than the channel capacity. An encoder capable of cyclical shifting of data, and which can therefore be used for Bose-Chaudhuri and Hocquenghem ...

Audiovisual semantic congruency during encoding enhances memory performance.

Science.gov (United States)

Heikkilä, Jenni; Alho, Kimmo; Hyvönen, Heidi; Tiippana, Kaisa

2015-01-01

Studies of memory and learning have usually focused on a single sensory modality, although human perception is multisensory in nature. In the present study, we investigated the effects of audiovisual encoding on later unisensory recognition memory performance. The participants were to memorize auditory or visual stimuli (sounds, pictures, spoken words, or written words), each of which co-occurred with either a semantically congruent stimulus, incongruent stimulus, or a neutral (non-semantic noise) stimulus in the other modality during encoding. Subsequent memory performance was overall better when the stimulus to be memorized was initially accompanied by a semantically congruent stimulus in the other modality than when it was accompanied by a neutral stimulus. These results suggest that semantically congruent multisensory experiences enhance encoding of both nonverbal and verbal materials, resulting in an improvement in their later recognition memory.

Quantum Darwinism Requires an Extra-Theoretical Assumption of Encoding Redundancy

Science.gov (United States)

Fields, Chris

2010-10-01

Observers restricted to the observation of pointer states of apparatus cannot conclusively demonstrate that the pointer of an apparatus mathcal{A} registers the state of a system of interest S without perturbing S. Observers cannot, therefore, conclusively demonstrate that the states of a system S are redundantly encoded by pointer states of multiple independent apparatus without destroying the redundancy of encoding. The redundancy of encoding required by quantum Darwinism must, therefore, be assumed from outside the quantum-mechanical formalism and without the possibility of experimental demonstration.

Universal Quantum Computing with Arbitrary Continuous-Variable Encoding

OpenAIRE

Lau, Hoi-Kwan; Plenio, Martin B.

2016-01-01

Implementing a qubit quantum computer in continuous-variable systems conventionally requires the engineering of specific interactions according to the encoding basis states. In this work, we present a unified formalism to conduct universal quantum computation with a fixed set of operations but arbitrary encoding. By storing a qubit in the parity of two or four qumodes, all computing processes can be implemented by basis state preparations, continuous-variable exponential-swap operations, and ...

Design and implementation of parallel video encoding strategies using divisible load analysis

NARCIS (Netherlands)

Li, Ping; Veeravalli, Bharadwaj; Kassim, A.A.

2005-01-01

The processing time needed for motion estimation usually accounts for a significant part of the overall processing time of the video encoder. To improve the video encoding speed, reducing the execution time for motion estimation process is essential. Parallel implementation of video encoding systems

On the number of encoder states for a type of RLL codes

NARCIS (Netherlands)

Cai, K.; Schouhamer Immink, K.A.

2006-01-01

The relationship between the number of encoder states and the probable size of certain runlength-limited (RLL) codes is derived analytically. By associating the number of encoder states with (generalized) Fibonacci numbers, the minimum number of encoder states is obtained, which maximizes the rate

Towards an Automatic Parameter-Tuning Framework for Cost Optimization on Video Encoding Cloud

Directory of Open Access Journals (Sweden)

Xiaowei Li

2012-01-01

Full Text Available The emergence of cloud encoding services facilitates many content owners, such as the online video vendors, to transcode their digital videos without infrastructure setup. Such service provider charges the customers only based on their resource consumption. For both the service provider and customers, lowering the resource consumption while maintaining the quality is valuable and desirable. Thus, to choose a cost-effective encoding parameter, configuration is essential and challenging due to the tradeoff between bitrate, encoding speed, and resulting quality. In this paper, we explore the feasibility of an automatic parameter-tuning framework, based on which the above objective can be achieved. We introduce a simple service model, which combines the bitrate and encoding speed into a single value: encoding cost. Then, we conduct an empirical study to examine the relationship between the encoding cost and various parameter settings. Our experiment is based on the one-pass Constant Rate Factor method in x264, which can achieve relatively stable perceptive quality, and we vary each parameter we choose to observe how the encoding cost changes. The experiment results show that the tested parameters can be independently tuned to minimize the encoding cost, which makes the automatic parameter-tuning framework feasible and promising for optimizing the cost on video encoding cloud.

Interaction Between Encoding and Retrieval Operations in Cued Recall

Science.gov (United States)

Fisher, Ronald P.; Craik, Fergus I. M.

1977-01-01

Three experiments are described in which the qualitative nature of memorial processing was manipulated at both input (encoding) and output (retrieval). As in earlier research, it was found that retention levels were highest when the same type of information was used as a retrieval cue. Concludes that the notions of encoding specificity and depth…

Least-squares reverse time migration of marine data with frequency-selection encoding

KAUST Repository

Dai, Wei

2013-08-20

The phase-encoding technique can sometimes increase the efficiency of the least-squares reverse time migration (LSRTM) by more than one order of magnitude. However, traditional random encoding functions require all the encoded shots to share the same receiver locations, thus limiting the usage to seismic surveys with a fixed spread geometry. We implement a frequency-selection encoding strategy that accommodates data with a marine streamer geometry. The encoding functions are delta functions in the frequency domain, so that all the en- coded shots have unique non-overlapping frequency content, and the receivers can distinguish the wavefield from each shot with a unique frequency band. Since the encoding functions are orthogonal to each other, there will be no crosstalk between different shots during modeling and migration. With the frequency-selection encoding method, the computational efficiency of LSRTM is increased so that its cost is compara- ble to conventional RTM for both the Marmousi2 model and a marine data set recorded in the Gulf of Mexico. With more iterations, the LSRTM image quality is further improved. We conclude that LSRTM with frequency-selection is an efficient migration method that can sometimes produce more focused images than conventional RTM.

Role of Virus-Encoded microRNAs in Avian Viral Diseases

Directory of Open Access Journals (Sweden)

Yongxiu Yao

2014-03-01

Full Text Available With total dependence on the host cell, several viruses have adopted strategies to modulate the host cellular environment, including the modulation of microRNA (miRNA pathway through virus-encoded miRNAs. Several avian viruses, mostly herpesviruses, have been shown to encode a number of novel miRNAs. These include the highly oncogenic Marek’s disease virus-1 (26 miRNAs, avirulent Marek’s disease virus-2 (36 miRNAs, herpesvirus of turkeys (28 miRNAs, infectious laryngotracheitis virus (10 miRNAs, duck enteritis virus (33 miRNAs and avian leukosis virus (2 miRNAs. Despite the closer antigenic and phylogenetic relationship among some of the herpesviruses, miRNAs encoded by different viruses showed no sequence conservation, although locations of some of the miRNAs were conserved within the repeat regions of the genomes. However, some of the virus-encoded miRNAs showed significant sequence homology with host miRNAs demonstrating their ability to serve as functional orthologs. For example, mdv1-miR-M4-5p, a functional ortholog of gga-miR-155, is critical for the oncogenicity of Marek’s disease virus. Additionally, we also describe the potential association of the recently described avian leukosis virus subgroup J encoded E (XSR miRNA in the induction of myeloid tumors in certain genetically-distinct chicken lines. In this review, we describe the advances in our understanding on the role of virus-encoded miRNAs in avian diseases.

Encoding information into precipitation structures

International Nuclear Information System (INIS)

Martens, Kirsten; Bena, Ioana; Droz, Michel; Rácz, Zoltan

2008-01-01

Material design at submicron scales would be profoundly affected if the formation of precipitation patterns could be easily controlled. It would allow the direct building of bulk structures, in contrast to traditional techniques which consist of removing material in order to create patterns. Here, we discuss an extension of our recent proposal of using electrical currents to control precipitation bands which emerge in the wake of reaction fronts in A + + B – → C reaction–diffusion processes. Our main result, based on simulating the reaction–diffusion–precipitation equations, is that the dynamics of the charged agents can be guided by an appropriately designed time-dependent electric current so that, in addition to the control of the band spacing, the width of the precipitation bands can also be tuned. This makes straightforward the encoding of information into precipitation patterns and, as an amusing example, we demonstrate the feasibility by showing how to encode a musical rhythm

Power calculation of linear and angular incremental encoders

Science.gov (United States)

Prokofev, Aleksandr V.; Timofeev, Aleksandr N.; Mednikov, Sergey V.; Sycheva, Elena A.

2016-04-01

Automation technology is constantly expanding its role in improving the efficiency of manufacturing and testing processes in all branches of industry. More than ever before, the mechanical movements of linear slides, rotary tables, robot arms, actuators, etc. are numerically controlled. Linear and angular incremental photoelectric encoders measure mechanical motion and transmit the measured values back to the control unit. The capabilities of these systems are undergoing continual development in terms of their resolution, accuracy and reliability, their measuring ranges, and maximum speeds. This article discusses the method of power calculation of linear and angular incremental photoelectric encoders, to find the optimum parameters for its components, such as light emitters, photo-detectors, linear and angular scales, optical components etc. It analyzes methods and devices that permit high resolutions in the order of 0.001 mm or 0.001°, as well as large measuring lengths of over 100 mm. In linear and angular incremental photoelectric encoders optical beam is usually formulated by a condenser lens passes through the measuring unit changes its value depending on the movement of a scanning head or measuring raster. Past light beam is converting into an electrical signal by the photo-detecter's block for processing in the electrical block. Therefore, for calculating the energy source is a value of the desired value of the optical signal at the input of the photo-detecter's block, which reliably recorded and processed in the electronic unit of linear and angular incremental optoelectronic encoders. Automation technology is constantly expanding its role in improving the efficiency of manufacturing and testing processes in all branches of industry. More than ever before, the mechanical movements of linear slides, rotary tables, robot arms, actuators, etc. are numerically controlled. Linear and angular incremental photoelectric encoders measure mechanical motion and

Information transfer via implicit encoding with delay time modulation in a time-delay system

Energy Technology Data Exchange (ETDEWEB)

Kye, Won-Ho, E-mail: whkye@kipo.go.kr [Korean Intellectual Property Office, Government Complex Daejeon Building 4, 189, Cheongsa-ro, Seo-gu, Daejeon 302-701 (Korea, Republic of)

2012-08-20

A new encoding scheme for information transfer with modulated delay time in a time-delay system is proposed. In the scheme, the message is implicitly encoded into the modulated delay time. The information transfer rate as a function of encoding redundancy in various noise scales is presented and it is analyzed that the implicit encoding scheme (IES) has stronger resistance against channel noise than the explicit encoding scheme (EES). In addition, its advantages in terms of secure communication and feasible applications are discussed. -- Highlights: ► We propose new encoding scheme with delay time modulation. ► The message is implicitly encoded with modulated delay time. ► The proposed scheme shows stronger resistance against channel noise.

Low Complexity Encoder of High Rate Irregular QC-LDPC Codes for Partial Response Channels

Directory of Open Access Journals (Sweden)

IMTAWIL, V.

2011-11-01

Full Text Available High rate irregular QC-LDPC codes based on circulant permutation matrices, for efficient encoder implementation, are proposed in this article. The structure of the code is an approximate lower triangular matrix. In addition, we present two novel efficient encoding techniques for generating redundant bits. The complexity of the encoder implementation depends on the number of parity bits of the code for the one-stage encoding and the length of the code for the two-stage encoding. The advantage of both encoding techniques is that few XOR-gates are used in the encoder implementation. Simulation results on partial response channels also show that the BER performance of the proposed code has gain over other QC-LDPC codes.

Molecular cloning and functional analysis of the gene encoding ...

African Journals Online (AJOL)

Here we report for the first time the cloning of a full-length cDNA encoding GGPPS (Jc-GGPPS) from Jatropha curcas L. The full-length cDNA was 1414 base pair (bp), with an 1110-bp open reading frame (ORF) encoding a 370- amino-acids polypeptide. Bioinformatic analysis revealed that Jc-GGPPS is a member of the ...

A 10 Gbit/s OCDMA system based on electric encoding and optical transmission

Science.gov (United States)

Li, Chuan-qi; Hu, Jin-lin; He, Dong-dong; Chen, Mei-juan; Wang, Da-chi; Chen, Yan

2013-11-01

An electric encoded/optical transmission system of code division multiple access (CDMA) is proposed. It encodes the user signal in electric domain, and transfers the different code slice signals via the different wavelengths of light. This electric domain encoder/decoder is compared with current traditional encoder/decoder. Four-user modulation/demodulation optical CDMA (OCDMA) system with rate of 2.5 Gbit/s is simulated, which is based on the optical orthogonal code (OCC) designed in our laboratory. The results show that the structure of electric encoding/optical transmission can encode/decode signal correctly, and can achieve the chip rate equal to the user data rate. It can overcome the rate limitation of electronic bottleneck, and bring some potential applications in the electro-optical OCDMA system.

Divided attention reduces resistance to distraction at encoding but not retrieval.

Science.gov (United States)

Weeks, Jennifer C; Hasher, Lynn

2017-08-01

Older adults show implicit memory for previously seen distraction, an effect attributed to poor attentional control. It is unclear whether this effect results from lack of control over encoding during the distraction task, lack of retrieval constraint during the test task, or both. In the present study, we simulated poor distraction control in young adults using divided attention at encoding, at retrieval, at both times, or not at all. The encoding task was a 1-back task on pictures with distracting superimposed letter strings, some of which were words. The retrieval task was a word fragment completion task testing implicit memory for the distracting words. Attention was divided using an auditory odd digit detection task. Dividing attention at encoding, but not at retrieval, resulted in significant priming for distraction, which suggests that control over encoding processes is a primary determinant of distraction transfer in populations with low inhibitory control (e.g. older adults).

Factors affecting reorganisation of memory encoding networks in temporal lobe epilepsy

Science.gov (United States)

Sidhu, M.K.; Stretton, J.; Winston, G.P.; Symms, M.; Thompson, P.J.; Koepp, M.J.; Duncan, J.S.

2015-01-01

Summary Aims In temporal lobe epilepsy (TLE) due to hippocampal sclerosis reorganisation in the memory encoding network has been consistently described. Distinct areas of reorganisation have been shown to be efficient when associated with successful subsequent memory formation or inefficient when not associated with successful subsequent memory. We investigated the effect of clinical parameters that modulate memory functions: age at onset of epilepsy, epilepsy duration and seizure frequency in a large cohort of patients. Methods We studied 53 patients with unilateral TLE and hippocampal sclerosis (29 left). All participants performed a functional magnetic resonance imaging memory encoding paradigm of faces and words. A continuous regression analysis was used to investigate the effects of age at onset of epilepsy, epilepsy duration and seizure frequency on the activation patterns in the memory encoding network. Results Earlier age at onset of epilepsy was associated with left posterior hippocampus activations that were involved in successful subsequent memory formation in left hippocampal sclerosis patients. No association of age at onset of epilepsy was seen with face encoding in right hippocampal sclerosis patients. In both left hippocampal sclerosis patients during word encoding and right hippocampal sclerosis patients during face encoding, shorter duration of epilepsy and lower seizure frequency were associated with medial temporal lobe activations that were involved in successful memory formation. Longer epilepsy duration and higher seizure frequency were associated with contralateral extra-temporal activations that were not associated with successful memory formation. Conclusion Age at onset of epilepsy influenced verbal memory encoding in patients with TLE due to hippocampal sclerosis in the speech-dominant hemisphere. Shorter duration of epilepsy and lower seizure frequency were associated with less disruption of the efficient memory encoding network whilst

Task-selective memory effects for successfully implemented encoding strategies.

Science.gov (United States)

Leshikar, Eric D; Duarte, Audrey; Hertzog, Christopher

2012-01-01

Previous behavioral evidence suggests that instructed strategy use benefits associative memory formation in paired associate tasks. Two such effective encoding strategies--visual imagery and sentence generation--facilitate memory through the production of different types of mediators (e.g., mental images and sentences). Neuroimaging evidence suggests that regions of the brain support memory reflecting the mental operations engaged at the time of study. That work, however, has not taken into account self-reported encoding task success (i.e., whether participants successfully generated a mediator). It is unknown, therefore, whether task-selective memory effects specific to each strategy might be found when encoding strategies are successfully implemented. In this experiment, participants studied pairs of abstract nouns under either visual imagery or sentence generation encoding instructions. At the time of study, participants reported their success at generating a mediator. Outside of the scanner, participants further reported the quality of the generated mediator (e.g., images, sentences) for each word pair. We observed task-selective memory effects for visual imagery in the left middle occipital gyrus, the left precuneus, and the lingual gyrus. No such task-selective effects were observed for sentence generation. Intriguingly, activity at the time of study in the left precuneus was modulated by the self-reported quality (vividness) of the generated mental images with greater activity for trials given higher ratings of quality. These data suggest that regions of the brain support memory in accord with the encoding operations engaged at the time of study.

Direct encoding of orientation variance in the visual system.

Science.gov (United States)

Norman, Liam J; Heywood, Charles A; Kentridge, Robert W

2015-01-01

Our perception of regional irregularity, an example of which is orientation variance, seems effortless when we view two patches of texture that differ in this attribute. Little is understood, however, of how the visual system encodes a regional statistic like orientation variance, but there is some evidence to suggest that it is directly encoded by populations of neurons tuned broadly to high or low levels. The present study shows that selective adaptation to low or high levels of variance results in a perceptual aftereffect that shifts the perceived level of variance of a subsequently viewed texture in the direction away from that of the adapting stimulus (Experiments 1 and 2). Importantly, the effect is durable across changes in mean orientation, suggesting that the encoding of orientation variance is independent of global first moment orientation statistics (i.e., mean orientation). In Experiment 3 it was shown that the variance-specific aftereffect did not show signs of being encoded in a spatiotopic reference frame, similar to the equivalent aftereffect of adaptation to the first moment orientation statistic (the tilt aftereffect), which is represented in the primary visual cortex and exists only in retinotopic coordinates. Experiment 4 shows that a neuropsychological patient with damage to ventral areas of the cortex but spared intact early areas retains sensitivity to orientation variance. Together these results suggest that orientation variance is encoded directly by the visual system and possibly at an early cortical stage.

Feedback-tuned, noise resilient gates for encoded spin qubits

Science.gov (United States)

Bluhm, Hendrik

Spin 1/2 particles form native two level systems and thus lend themselves as a natural qubit implementation. However, encoding a single qubit in several spins entails benefits, such as reducing the resources necessary for qubit control and protection from certain decoherence channels. While several varieties of such encoded spin qubits have been implemented, accurate control remains challenging, and leakage out of the subspace of valid qubit states is a potential issue. Optimal performance typically requires large pulse amplitudes for fast control, which is prone to systematic errors and prohibits standard control approaches based on Rabi flopping. Furthermore, the exchange interaction typically used to electrically manipulate encoded spin qubits is inherently sensitive to charge noise. I will discuss all-electrical, high-fidelity single qubit operations for a spin qubit encoded in two electrons in a GaAs double quantum dot. Starting from a set of numerically optimized control pulses, we employ an iterative tuning procedure based on measured error syndromes to remove systematic errors.Randomized benchmarking yields an average gate fidelity exceeding 98 % and a leakage rate into invalid states of 0.2 %. These gates exhibit a certain degree of resilience to both slow charge and nuclear spin fluctuations due to dynamical correction analogous to a spin echo. Furthermore, the numerical optimization minimizes the impact of fast charge noise. Both types of noise make relevant contributions to gate errors. The general approach is also adaptable to other qubit encodings and exchange based two-qubit gates.

Nonlinear inversion of potential-field data using a hybrid-encoding genetic algorithm

Science.gov (United States)

Chen, C.; Xia, J.; Liu, J.; Feng, G.

2006-01-01

Using a genetic algorithm to solve an inverse problem of complex nonlinear geophysical equations is advantageous because it does not require computer gradients of models or "good" initial models. The multi-point search of a genetic algorithm makes it easier to find the globally optimal solution while avoiding falling into a local extremum. As is the case in other optimization approaches, the search efficiency for a genetic algorithm is vital in finding desired solutions successfully in a multi-dimensional model space. A binary-encoding genetic algorithm is hardly ever used to resolve an optimization problem such as a simple geophysical inversion with only three unknowns. The encoding mechanism, genetic operators, and population size of the genetic algorithm greatly affect search processes in the evolution. It is clear that improved operators and proper population size promote the convergence. Nevertheless, not all genetic operations perform perfectly while searching under either a uniform binary or a decimal encoding system. With the binary encoding mechanism, the crossover scheme may produce more new individuals than with the decimal encoding. On the other hand, the mutation scheme in a decimal encoding system will create new genes larger in scope than those in the binary encoding. This paper discusses approaches of exploiting the search potential of genetic operations in the two encoding systems and presents an approach with a hybrid-encoding mechanism, multi-point crossover, and dynamic population size for geophysical inversion. We present a method that is based on the routine in which the mutation operation is conducted in the decimal code and multi-point crossover operation in the binary code. The mix-encoding algorithm is called the hybrid-encoding genetic algorithm (HEGA). HEGA provides better genes with a higher probability by a mutation operator and improves genetic algorithms in resolving complicated geophysical inverse problems. Another significant

An electrophysiological investigation of memory encoding, depth of processing, and word frequency in humans.

Science.gov (United States)

Guo, Chunyan; Zhu, Ying; Ding, Jinhong; Fan, Silu; Paller, Ken A

2004-02-12

Memory encoding can be studied by monitoring brain activity correlated with subsequent remembering. To understand brain potentials associated with encoding, we compared multiple factors known to affect encoding. Depth of processing was manipulated by requiring subjects to detect animal names (deep encoding) or boldface (shallow encoding) in a series of Chinese words. Recognition was more accurate with deep than shallow encoding, and for low- compared to high-frequency words. Potentials were generally more positive for subsequently recognized versus forgotten words; for deep compared to shallow processing; and, for remembered words only, for low- than for high-frequency words. Latency and topographic differences between these potentials suggested that several factors influence the effectiveness of encoding and can be distinguished using these methods, even with Chinese logographic symbols.

Error-free holographic frames encryption with CA pixel-permutation encoding algorithm

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Li, Xiaowei; Xiao, Dan; Wang, Qiong-Hua

2018-01-01

The security of video data is necessary in network security transmission hence cryptography is technique to make video data secure and unreadable to unauthorized users. In this paper, we propose a holographic frames encryption technique based on the cellular automata (CA) pixel-permutation encoding algorithm. The concise pixel-permutation algorithm is used to address the drawbacks of the traditional CA encoding methods. The effectiveness of the proposed video encoding method is demonstrated by simulation examples.

Fluorescence-Based Multiplex Protein Detection Using Optically Encoded Microbeads

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Dae Hong Jeong

2012-03-01

Full Text Available Potential utilization of proteins for early detection and diagnosis of various diseases has drawn considerable interest in the development of protein-based multiplex detection techniques. Among the various techniques for high-throughput protein screening, optically-encoded beads combined with fluorescence-based target monitoring have great advantages over the planar array-based multiplexing assays. This review discusses recent developments of analytical methods of screening protein molecules on microbead-based platforms. These include various strategies such as barcoded microbeads, molecular beacon-based techniques, and surface-enhanced Raman scattering-based techniques. Their applications for label-free protein detection are also addressed. Especially, the optically-encoded beads such as multilayer fluorescence beads and SERS-encoded beads are successful for generating a large number of coding.

Rapid duplication and loss of nbs-encoding genes in eurosids II

International Nuclear Information System (INIS)

Si, W.; Gu, L.; Yang, S.; Zhang, X.; Memon, S.

2015-01-01

Eurosids basically evolved from the core Eudicots Rosids. The Rosids consist of two large assemblages, Eurosids I (Fabids) and Eurosids II (Malvids), which belong to the largest group of Angiosperms, comprising of >40,000 and ∼ 15,000 species, respectively. Although the evolutionary patterns of the largest class of disease resistance genes consisting of a nucleotide binding site (NBS) and leucine-rich repeats (LRRs) have been studied in many species, systemic research of NBS-encoding genes has not been performed in different orders of Eurosids II. Here, five Eurosids II species, Gossypium raimondii, Theobroma cacao, Carica papaya, Citrus clementina, and Arabidopsis thaliana, distributing in three orders, were used to gain insights into the evolutionary patterns of the NBS-encoding genes. Our data showed that frequent copy number variations of NBS-encoding genes were found among these species. Phylogenetic tree analysis and the numbers of the NBS-encoding genes in the common ancestor of these species showed that species-specific NBS clades, including multi-copy and single copy numbers are dominant among these genes. However, not a single clade was found with only five copies, which come from all of the five species, respectively, suggesting rapid turn-over with birth and death of the NBS-encoding genes among Eurosids II species. In addition, a strong positive correlation was observed between the Toll/interleukin receptor (TIR)) type NBS-encoding genes and species-specific genes, indicating rapid gene loss and duplication. Whereas, non- TIR type NBS-encoding genes in these five species showed two distinct evolutionary patterns. (author)

Genetic spectrum of low density lipoprotein receptor gene variations in South Indian population.

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ArulJothi, K N; Suruthi Abirami, B; Devi, Arikketh

2018-03-01

Low density lipoprotein receptor (LDLR) is a membrane bound receptor maintaining cholesterol homeostasis along with Apolipoprotein B (APOB), Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) and other genes of lipid metabolism. Any pathogenic variation in these genes alters the function of the receptor and leads to Familial Hypercholesterolemia (FH) and other cardiovascular diseases. This study was aimed at screening the LDLR, APOB and PCSK9 genes in Hypercholesterolemic patients to define the genetic spectrum of FH in Indian population. Familial Hypercholesterolemia patients (n=78) of South Indian Tamil population with LDL cholesterol and Total cholesterol levels above 4.9mmol/l and 7.5mmol/l with family history of Myocardial infarction were involved. DNA was isolated by organic extraction method from blood samples and LDLR, APOB and PCSK9 gene exons were amplified using primers that cover exon-intron boundaries. The amplicons were screened using High Resolution Melt (HRM) Analysis and the screened samples were sequenced after purification. This study reports 20 variations in South Indian population for the first time. In this set of variations 9 are novel variations which are reported for the first time, 11 were reported in other studies also. The in silico analysis for all the variations detected in this study were done to predict the probabilistic effect in pathogenicity of FH. This study adds 9 novel variations and 11 recurrent variations to the spectrum of LDLR gene mutations in Indian population. All these variations are reported for the first time in Indian population. This spectrum of variations was different from the variations of previous Indian reports. Copyright © 2017 Elsevier B.V. All rights reserved.

Phytosterols, Phytostanols, and Lipoprotein Metabolism

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Helena Gylling

2015-09-01

Full Text Available The efficacy of phytosterols and phytostanols added to foods and food supplements to obtain significant non-pharmacologic serum and low density lipoprotein (LDL cholesterol reduction is well documented. Irrespective of age, gender, ethnic background, body weight, background diet, or the cause of hypercholesterolemia and, even added to statin treatment, phytosterols and phytostanols at 2 g/day significantly lower LDL cholesterol concentration by 8%–10%. They do not affect the concentrations of high density lipoprotein cholesterol, lipoprotein (a or serum proprotein convertase subtilisin/kexin type 9. In some studies, phytosterols and phytostanols have modestly reduced serum triglyceride levels especially in subjects with slightly increased baseline concentrations. Phytosterols and phytostanols lower LDL cholesterol by displacing cholesterol from mixed micelles in the small intestine so that cholesterol absorption is partially inhibited. Cholesterol absorption and synthesis have been carefully evaluated during phytosterol and phytostanol supplementation. However, only a few lipoprotein kinetic studies have been performed, and they revealed that LDL apoprotein B-100 transport rate was reduced. LDL particle size was unchanged, but small dense LDL cholesterol concentration was reduced. In subjects with metabolic syndrome and moderate hypertriglyceridemia, phytostanols reduced not only non- high density lipoprotein (HDL cholesterol concentration but also serum triglycerides by 27%, and reduced the large and medium size very low density lipoprotein particle concentrations. In the few postprandial studies, the postprandial lipoproteins were reduced, but detailed studies with apoprotein B-48 are lacking. In conclusion, more kinetic studies are required to obtain a more complete understanding of the fasting and postprandial lipoprotein metabolism caused by phytosterols and phytostanols. It seems obvious, however, that the most atherogenic lipoprotein

Phytosterols, Phytostanols, and Lipoprotein Metabolism.

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Gylling, Helena; Simonen, Piia

2015-09-17

The efficacy of phytosterols and phytostanols added to foods and food supplements to obtain significant non-pharmacologic serum and low density lipoprotein (LDL) cholesterol reduction is well documented. Irrespective of age, gender, ethnic background, body weight, background diet, or the cause of hypercholesterolemia and, even added to statin treatment, phytosterols and phytostanols at 2 g/day significantly lower LDL cholesterol concentration by 8%-10%. They do not affect the concentrations of high density lipoprotein cholesterol, lipoprotein (a) or serum proprotein convertase subtilisin/kexin type 9. In some studies, phytosterols and phytostanols have modestly reduced serum triglyceride levels especially in subjects with slightly increased baseline concentrations. Phytosterols and phytostanols lower LDL cholesterol by displacing cholesterol from mixed micelles in the small intestine so that cholesterol absorption is partially inhibited. Cholesterol absorption and synthesis have been carefully evaluated during phytosterol and phytostanol supplementation. However, only a few lipoprotein kinetic studies have been performed, and they revealed that LDL apoprotein B-100 transport rate was reduced. LDL particle size was unchanged, but small dense LDL cholesterol concentration was reduced. In subjects with metabolic syndrome and moderate hypertriglyceridemia, phytostanols reduced not only non- high density lipoprotein (HDL) cholesterol concentration but also serum triglycerides by 27%, and reduced the large and medium size very low density lipoprotein particle concentrations. In the few postprandial studies, the postprandial lipoproteins were reduced, but detailed studies with apoprotein B-48 are lacking. In conclusion, more kinetic studies are required to obtain a more complete understanding of the fasting and postprandial lipoprotein metabolism caused by phytosterols and phytostanols. It seems obvious, however, that the most atherogenic lipoprotein particles will be

Mechanism of Folding and Activation of Subtilisin Kexin Isozyme-1 (SKI-1)/Site-1 Protease (S1P).

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da Palma, Joel Ramos; Cendron, Laura; Seidah, Nabil Georges; Pasquato, Antonella; Kunz, Stefan

2016-01-29

The proprotein convertase subtilisin kexin isozyme-1 (SKI-1)/site-1 protease (S1P) is implicated in lipid homeostasis, the unfolded protein response, and lysosome biogenesis. The protease is further hijacked by highly pathogenic emerging viruses for the processing of their envelope glycoproteins. Zymogen activation of SKI-1/S1P requires removal of an N-terminal prodomain, by a multistep process, generating the mature enzyme. Here, we uncover a modular structure of the human SKI-1/S1P prodomain and define its function in folding and activation. We provide evidence that the N-terminal AB fragment of the prodomain represents an autonomous structural and functional unit that is necessary and sufficient for folding and partial activation. In contrast, the C-terminal BC fragment lacks a defined structure but is crucial for autoprocessing and full catalytic activity. Phylogenetic analysis revealed that the sequence of the AB domain is highly conserved, whereas the BC fragment shows considerable variation and seems even absent in some species. Notably, SKI-1/S1P of arthropods, like the fruit fly Drosophila melanogaster, contains a shorter prodomain comprised of full-length AB and truncated BC regions. Swapping the prodomain fragments between fly and human resulted in a fully mature and active SKI-1/S1P chimera. Our study suggests that primordial SKI-1/S1P likely contained a simpler prodomain consisting of the highly conserved AB fragment that represents an independent folding unit. The BC region appears as a later evolutionary acquisition, possibly allowing more subtle fine-tuning of the maturation process. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Current treatment of dyslipidaemia: PCSK9 inhibitors and statin intolerance.

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Koskinas, Konstantinos; Wilhelm, Matthias; Windecker, Stephan

2016-01-01

Statins are the cornerstone of the management of dyslipidaemias and prevention of cardiovascular disease. Although statins are, overall, safe and well tolerated, adverse events can occur and constitute an important barrier to maintaining long-term adherence to statin treatment. In patients who cannot tolerate statins, alternative treatments include switch to another statin, intermittent-dosage regimens and non-statin lipid-lowering medications. Nonetheless, a high proportion of statin-intolerant patients are unable to achieve recommended low-density lipoprotein (LDL) cholesterol goals, thereby resulting in substantial residual cardiovascular risk. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a protease implicated in LDL receptor degradation and plays a central role in cholesterol metabolism. In recent studies, PCSK9 inhibition by means of monoclonal antibodies achieved LDL cholesterol reductions of 50% to 70% across various patient populations and background lipid-lowering therapies, while maintaining a favourable safety profile. The efficacy and safety of the monoclonal antibodies alirocumab and evolocumab were confirmed in statin-intolerant patients, indicating that PCSK9 inhibitors represent an attractive treatment option in this challenging clinical setting. PCSK9 inhibitors recently received regulatory approval for clinical use and may be considered in properly selected patients according to current consensus documents, including patients with statin intolerance. In this review we summarise current evidence regarding diagnostic evaluation of statin-related adverse events, particularly statin-associated muscle symptoms, and we discuss current recommendations on the management of statin-intolerant patients. In view of emerging evidence of the efficacy and safety of PCSK9 inhibitors, we further discuss the role of monoclonal PCSK9 antibodies in the management of statin-intolerant hypercholesterolaemic patients.

Upregulation of CPE promotes cell proliferation and tumorigenicity in colorectal cancer

International Nuclear Information System (INIS)

Liang, Xing-Hua; He, Wen-guang; Huang, Yan-Nian; Zeng, Xian-Cheng; Li, Ling-ling; Wu, Geng-Gang; Xie, Yi-Cheng; Zhang, Guang-Xian; Chen, Wei; Yang, Hai-Feng; Liu, Qi-Long; Li, Wen-Hong

2013-01-01

Colorectal cancer (CRC) is one of the most common cancers worldwide and a leading cause of cancer related death. Although the mortality rate of CRC is decreasing, finding novel targets for its therapy remains urgent. Carboxypeptidase E (CPE), a member of the pro-protein convertases, which are involved in the maturation of protein precursors, has recently been reported as elevated in many types of cancer. However, its role and mechanisms in tumor progression are poorly understood. In the present study, we investigated expression of CPE in CRC cell lines and tumor tissues using Western blot and real-time qRT-PCR. Plasmids for overexpression and depletion of CPE were constructed and analyzed by Western blot, MTT and colony formation assays and bromodeoxyuridine incorporation assays. The relative expression of p21, p27, and cyclin D1 were analyzed by Real-time qRT-PCR in the indicated cells. Our study showed that CPE was significantly upregulated in CRC cell lines and tumor tissues. MTT and colony formation assays indicated that overexpression of CPE enhanced cell growth rates. BrdU incorporation and flow-cytometry assays showed that ectopic expression of CPE increased the S-phase fraction cells. Soft agar assay proved enhanced tumorigenicity activity in CPE over-expressing CRC cells. Further studies of the molecular mechanisms of CPE indicated that is promoted cell proliferation and tumorigenicity through downregulation of p21 and p27, and upregulation of cyclin D1. Taken together, these data suggest that CPE plays an important role in cell cycle regulation and tumorigenicity, and may serve as a potential target for CRC therapeutics

Circulating PCSK9 affects serum LDL and cholesterol levels more than SREBP-2 expression.

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Mohammadi, Asghar; Shabani, Mohamad; Naseri, Faezeh; Hosseni, Bita; Soltanmohammadi, Elham; Piran, Sadegh; Najafi, Mohammad

2017-07-01

Cholesterol homeostasis is dependent upon the sterol regulatory element binding protein 2 (SREBP-2) regulatory system and the functioning of plasma proprotein convertase subtilisin/kexin type 9 (PCSK9). Many studies have also reported that low density lipoprotein receptor (LDLR) levels in cellular membranes are related to the functioning of these proteins. The aim of this study was to investigate the association of lipid profiles with circulating PCSK9 protein values and SREBP-2 expression levels in normal subjects. The study involved 120 randomly chosen healthy subjects. Their lipid profiles were measured using routine laboratory techniques, and the plasma PCSK9 protein and SREBP-2 expression levels were determined by ELISA and real time quantitative PCR methods, respectively. A statistical analysis was carried out using a statistical software package. Linear regression analyses showed a significant correlation between total cholesterol and PCSK9 (3.54 ± 1.31 ng/mL), as well as between total cholesterol and SREBP-2 (0.1-35.38) (p = 0.002 and p = 0.02, respectively). Furthermore, multiple regression analyses showed strict correlations between PCSK9 and cholesterol-related parameters especially the total cholesterol/HDL-C ratio (β = 3.53, p = 0.001). There was no significant correlation between circulating PCSK9 and SREBP-2 expression levels (r = 1.2, p = 0.3). The study results revealed that serum cholesterol-related parameters are strictly associated with plasma PCSK9 values, suggesting that PCSK9 function has a greater effect on serum total cholesterol levels than SREBP-2 expression does. Furthermore, the total cholesterol/HDL-C ratio was a better indicator for evaluating PCSK9 level than total cholesterol.

The biology of PCSK9 from the endoplasmic reticulum to lysosomes: new and emerging therapeutics to control low-density lipoprotein cholesterol

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Poirier S

2013-10-01

Full Text Available Steve Poirier,1,2 Gaétan Mayer1–31Laboratory of Molecular Cell Biology, Montreal Heart Institute, Montréal, QC, Canada; 2Départements de Pharmacologie, 3Médecine, Faculté de Médecine, Université de Montréal, Montréal, QC, CanadaAbstract: Proprotein convertase subtilisin/kexin type 9 (PCSK9 directly binds to the epidermal growth factor-like repeat A domain of low-density lipoprotein receptor and induces its degradation, thereby controlling circulating low-density lipoprotein cholesterol (LDL-C concentration. Heterozygous loss-of-function mutations in PCSK9 can decrease the incidence of coronary heart disease by up to 88%, owing to lifelong reduction of LDL-C. Moreover, two subjects with PCSK9 loss-of-function mutations on both alleles, resulting in a total absence of functional PCSK9, were found to have extremely low circulating LDL-C levels without other apparent abnormalities. Accordingly, PCSK9 could represent a safe and effective pharmacological target to increase clearance of LDL-C and to reduce the risk of coronary heart disease. Recent clinical trials using anti-PCSK9 monoclonal antibodies that block the PCSK9:low-density lipoprotein receptor interaction were shown to considerably reduce LDL-C levels by up to 65% when given alone and by up to 72% in patients already receiving statin therapy. In this review, we will discuss how major scientific breakthroughs in PCSK9 cell biology have led to the development of new and forthcoming LDL-C-lowering pharmacological agents.Keywords: PCSK9, LDLR, LDL-cholesterol, lipoproteins, coronary heart disease, inhibitors, monoclonal antibody therapy

Age-related effects on perceptual and semantic encoding in memory.

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Kuo, M C C; Liu, K P Y; Ting, K H; Chan, C C H

2014-03-07

This study examined the age-related subsequent memory effect (SME) in perceptual and semantic encoding using event-related potentials (ERPs). Seventeen younger adults and 17 older adults studied a series of Chinese characters either perceptually (by inspecting orthographic components) or semantically (by determining whether the depicted object makes sounds). The two tasks had similar levels of difficulty. The participants made studied or unstudied judgments during the recognition phase. Younger adults performed better in both conditions, with significant SMEs detected in the time windows of P2, N3, P550, and late positive component (LPC). In the older group, SMEs were observed in the P2 and N3 latencies in both conditions but were only detected in the P550 in the semantic condition. Between-group analyses showed larger frontal and central SMEs in the younger sample in the LPC latency regardless of encoding type. Aging effect appears to be stronger on influencing perceptual than semantic encoding processes. The effects seem to be associated with a decline in updating and maintaining representations during perceptual encoding. The age-related decline in the encoding function may be due in part to changes in frontal lobe function. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

Attention promotes episodic encoding by stabilizing hippocampal representations

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Aly, Mariam; Turk-Browne, Nicholas B.

2016-01-01

Attention influences what is later remembered, but little is known about how this occurs in the brain. We hypothesized that behavioral goals modulate the attentional state of the hippocampus to prioritize goal-relevant aspects of experience for encoding. Participants viewed rooms with paintings, attending to room layouts or painting styles on different trials during high-resolution functional MRI. We identified template activity patterns in each hippocampal subfield that corresponded to the attentional state induced by each task. Participants then incidentally encoded new rooms with art while attending to the layout or painting style, and memory was subsequently tested. We found that when task-relevant information was better remembered, the hippocampus was more likely to have been in the correct attentional state during encoding. This effect was specific to the hippocampus, and not found in medial temporal lobe cortex, category-selective areas of the visual system, or elsewhere in the brain. These findings provide mechanistic insight into how attention transforms percepts into memories. PMID:26755611

Distinctiveness and encoding effects in online sentence comprehension

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Philip eHofmeister

2014-12-01

Full Text Available In explicit memory recall and recognition tasks, elaboration and contextual isolation both facilitate memory performance. Here, we investigate these effects in the context of sentence processing: targets for retrieval during online sentence processing of English object relative clause constructions differ in the amount of elaboration associated with the target noun phrase, or the homogeneity of superficial features (text color. Experiment 1 shows that greater elaboration for targets during the encoding phase reduces reading times at retrieval sites, but elaboration of non-targets has considerably weaker effects. Experiment 2 illustrates that processing isolated superficial features of target noun phrases --- here, a green word in a sentence with words colored white --- does not lead to enhanced memory performance, despite triggering longer encoding times. These results are interpreted in the light of the memory models of Nairne 1990, 2001, 2006, which state that encoding remnants contribute to the set of retrieval cues that provide the basis for similarity-based interference effects.

Automatic Encoding and Language Detection in the GSDL

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Otakar Pinkas

2014-10-01

Full Text Available Automatic detection of encoding and language of the text is part of the Greenstone Digital Library Software (GSDL for building and distributing digital collections. It is developed by the University of Waikato (New Zealand in cooperation with UNESCO. The automatic encoding and language detection in Slavic languages is difficult and it sometimes fails. The aim is to detect cases of failure. The automatic detection in the GSDL is based on n-grams method. The most frequent n-grams for Czech are presented. The whole process of automatic detection in the GSDL is described. The input documents to test collections are plain texts encoded in ISO-8859-1, ISO-8859-2 and Windows-1250. We manually evaluated the quality of automatic detection. To the causes of errors belong the improper language model predominance and the incorrect switch to Windows-1250. We carried out further tests on documents that were more complex.

Encoding information using laguerre gaussian modes

CSIR Research Space (South Africa)

Trichili, A

2015-08-01

Full Text Available The authors experimentally demonstrate an information encoding protocol using the two degrees of freedom of Laguerre Gaussian modes having different radial and azimuthal components. A novel method, based on digital holography, for information...

Extraordinarily Adaptive Properties of the Genetically Encoded Amino Acids

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Ilardo, Melissa; Meringer, Markus; Freeland, Stephen; Rasulev, Bakhtiyor; Cleaves II, H. James

2015-01-01

Using novel advances in computational chemistry, we demonstrate that the set of 20 genetically encoded amino acids, used nearly universally to construct all coded terrestrial proteins, has been highly influenced by natural selection. We defined an adaptive set of amino acids as one whose members thoroughly cover relevant physico-chemical properties, or “chemistry space.” Using this metric, we compared the encoded amino acid alphabet to random sets of amino acids. These random sets were drawn from a computationally generated compound library containing 1913 alternative amino acids that lie within the molecular weight range of the encoded amino acids. Sets that cover chemistry space better than the genetically encoded alphabet are extremely rare and energetically costly. Further analysis of more adaptive sets reveals common features and anomalies, and we explore their implications for synthetic biology. We present these computations as evidence that the set of 20 amino acids found within the standard genetic code is the result of considerable natural selection. The amino acids used for constructing coded proteins may represent a largely global optimum, such that any aqueous biochemistry would use a very similar set. PMID:25802223

Extraordinarily adaptive properties of the genetically encoded amino acids.

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Ilardo, Melissa; Meringer, Markus; Freeland, Stephen; Rasulev, Bakhtiyor; Cleaves, H James

2015-03-24

Using novel advances in computational chemistry, we demonstrate that the set of 20 genetically encoded amino acids, used nearly universally to construct all coded terrestrial proteins, has been highly influenced by natural selection. We defined an adaptive set of amino acids as one whose members thoroughly cover relevant physico-chemical properties, or "chemistry space." Using this metric, we compared the encoded amino acid alphabet to random sets of amino acids. These random sets were drawn from a computationally generated compound library containing 1913 alternative amino acids that lie within the molecular weight range of the encoded amino acids. Sets that cover chemistry space better than the genetically encoded alphabet are extremely rare and energetically costly. Further analysis of more adaptive sets reveals common features and anomalies, and we explore their implications for synthetic biology. We present these computations as evidence that the set of 20 amino acids found within the standard genetic code is the result of considerable natural selection. The amino acids used for constructing coded proteins may represent a largely global optimum, such that any aqueous biochemistry would use a very similar set.

Parametric fMRI analysis of visual encoding in the human medial temporal lobe.

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Rombouts, S A; Scheltens, P; Machielson, W C; Barkhof, F; Hoogenraad, F G; Veltman, D J; Valk, J; Witter, M P

1999-01-01

A number of functional brain imaging studies indicate that the medial temporal lobe system is crucially involved in encoding new information into memory. However, most studies were based on differences in brain activity between encoding of familiar vs. novel stimuli. To further study the underlying cognitive processes, we applied a parametric design of encoding. Seven healthy subjects were instructed to encode complex color pictures into memory. Stimuli were presented in a parametric fashion at different rates, thus representing different loads of encoding. Functional magnetic resonance imaging (fMRI) was used to assess changes in brain activation. To determine the number of pictures successfully stored into memory, recognition scores were determined afterwards. During encoding, brain activation occurred in the medial temporal lobe, comparable to the results obtained by others. Increasing the encoding load resulted in an increase in the number of successfully stored items. This was reflected in a significant increase in brain activation in the left lingual gyrus, in the left and right parahippocampal gyrus, and in the right inferior frontal gyrus. This study shows that fMRI can detect changes in brain activation during variation of one aspect of higher cognitive tasks. Further, it strongly supports the notion that the human medial temporal lobe is involved in encoding novel visual information into memory.

Key management of the double random-phase-encoding method using public-key encryption

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Saini, Nirmala; Sinha, Aloka

2010-03-01

Public-key encryption has been used to encode the key of the encryption process. In the proposed technique, an input image has been encrypted by using the double random-phase-encoding method using extended fractional Fourier transform. The key of the encryption process have been encoded by using the Rivest-Shamir-Adelman (RSA) public-key encryption algorithm. The encoded key has then been transmitted to the receiver side along with the encrypted image. In the decryption process, first the encoded key has been decrypted using the secret key and then the encrypted image has been decrypted by using the retrieved key parameters. The proposed technique has advantage over double random-phase-encoding method because the problem associated with the transmission of the key has been eliminated by using public-key encryption. Computer simulation has been carried out to validate the proposed technique.

Toward a Better Compression for DNA Sequences Using Huffman Encoding.

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Al-Okaily, Anas; Almarri, Badar; Al Yami, Sultan; Huang, Chun-Hsi

2017-04-01

Due to the significant amount of DNA data that are being generated by next-generation sequencing machines for genomes of lengths ranging from megabases to gigabases, there is an increasing need to compress such data to a less space and a faster transmission. Different implementations of Huffman encoding incorporating the characteristics of DNA sequences prove to better compress DNA data. These implementations center on the concepts of selecting frequent repeats so as to force a skewed Huffman tree, as well as the construction of multiple Huffman trees when encoding. The implementations demonstrate improvements on the compression ratios for five genomes with lengths ranging from 5 to 50 Mbp, compared with the standard Huffman tree algorithm. The research hence suggests an improvement on all such DNA sequence compression algorithms that use the conventional Huffman encoding. The research suggests an improvement on all DNA sequence compression algorithms that use the conventional Huffman encoding. Accompanying software is publicly available (AL-Okaily, 2016 ).

Task-selective memory effects for successfully implemented encoding strategies.

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Eric D Leshikar

Full Text Available Previous behavioral evidence suggests that instructed strategy use benefits associative memory formation in paired associate tasks. Two such effective encoding strategies--visual imagery and sentence generation--facilitate memory through the production of different types of mediators (e.g., mental images and sentences. Neuroimaging evidence suggests that regions of the brain support memory reflecting the mental operations engaged at the time of study. That work, however, has not taken into account self-reported encoding task success (i.e., whether participants successfully generated a mediator. It is unknown, therefore, whether task-selective memory effects specific to each strategy might be found when encoding strategies are successfully implemented. In this experiment, participants studied pairs of abstract nouns under either visual imagery or sentence generation encoding instructions. At the time of study, participants reported their success at generating a mediator. Outside of the scanner, participants further reported the quality of the generated mediator (e.g., images, sentences for each word pair. We observed task-selective memory effects for visual imagery in the left middle occipital gyrus, the left precuneus, and the lingual gyrus. No such task-selective effects were observed for sentence generation. Intriguingly, activity at the time of study in the left precuneus was modulated by the self-reported quality (vividness of the generated mental images with greater activity for trials given higher ratings of quality. These data suggest that regions of the brain support memory in accord with the encoding operations engaged at the time of study.

AN ENCODING METHOD FOR COMPRESSING GEOGRAPHICAL COORDINATES IN 3D SPACE

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C. Qian

2017-09-01

Full Text Available This paper proposed an encoding method for compressing geographical coordinates in 3D space. By the way of reducing the length of geographical coordinates, it helps to lessen the storage size of geometry information. In addition, the encoding algorithm subdivides the whole space according to octree rules, which enables progressive transmission and loading. Three main steps are included in this method: (1 subdividing the whole 3D geographic space based on octree structure, (2 resampling all the vertices in 3D models, (3 encoding the coordinates of vertices with a combination of Cube Index Code (CIC and Geometry Code. A series of geographical 3D models were applied to evaluate the encoding method. The results showed that this method reduced the storage size of most test data by 90 % or even more under the condition of a speed of encoding and decoding. In conclusion, this method achieved a remarkable compression rate in vertex bit size with a steerable precision loss. It shall be of positive meaning to the web 3d map storing and transmission.

Low-complexity video encoding method for wireless image transmission in capsule endoscope.

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Takizawa, Kenichi; Hamaguchi, Kiyoshi

2010-01-01

This paper presents a low-complexity video encoding method applicable for wireless image transmission in capsule endoscopes. This encoding method is based on Wyner-Ziv theory, in which side information available at a transmitter is treated as side information at its receiver. Therefore complex processes in video encoding, such as estimation of the motion vector, are moved to the receiver side, which has a larger-capacity battery. As a result, the encoding process is only to decimate coded original data through channel coding. We provide a performance evaluation for a low-density parity check (LDPC) coding method in the AWGN channel.

Similar patterns of neural activity predict memory function during encoding and retrieval.

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Kragel, James E; Ezzyat, Youssef; Sperling, Michael R; Gorniak, Richard; Worrell, Gregory A; Berry, Brent M; Inman, Cory; Lin, Jui-Jui; Davis, Kathryn A; Das, Sandhitsu R; Stein, Joel M; Jobst, Barbara C; Zaghloul, Kareem A; Sheth, Sameer A; Rizzuto, Daniel S; Kahana, Michael J

2017-07-15

Neural networks that span the medial temporal lobe (MTL), prefrontal cortex, and posterior cortical regions are essential to episodic memory function in humans. Encoding and retrieval are supported by the engagement of both distinct neural pathways across the cortex and common structures within the medial temporal lobes. However, the degree to which memory performance can be determined by neural processing that is common to encoding and retrieval remains to be determined. To identify neural signatures of successful memory function, we administered a delayed free-recall task to 187 neurosurgical patients implanted with subdural or intraparenchymal depth electrodes. We developed multivariate classifiers to identify patterns of spectral power across the brain that independently predicted successful episodic encoding and retrieval. During encoding and retrieval, patterns of increased high frequency activity in prefrontal, MTL, and inferior parietal cortices, accompanied by widespread decreases in low frequency power across the brain predicted successful memory function. Using a cross-decoding approach, we demonstrate the ability to predict memory function across distinct phases of the free-recall task. Furthermore, we demonstrate that classifiers that combine information from both encoding and retrieval states can outperform task-independent models. These findings suggest that the engagement of a core memory network during either encoding or retrieval shapes the ability to remember the past, despite distinct neural interactions that facilitate encoding and retrieval. Copyright © 2017 Elsevier Inc. All rights reserved.

Semantic Congruence Accelerates the Onset of the Neural Signals of Successful Memory Encoding.

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Packard, Pau A; Rodríguez-Fornells, Antoni; Bunzeck, Nico; Nicolás, Berta; de Diego-Balaguer, Ruth; Fuentemilla, Lluís

2017-01-11

As the stream of experience unfolds, our memory system rapidly transforms current inputs into long-lasting meaningful memories. A putative neural mechanism that strongly influences how input elements are transformed into meaningful memory codes relies on the ability to integrate them with existing structures of knowledge or schemas. However, it is not yet clear whether schema-related integration neural mechanisms occur during online encoding. In the current investigation, we examined the encoding-dependent nature of this phenomenon in humans. We showed that actively integrating words with congruent semantic information provided by a category cue enhances memory for words and increases false recall. The memory effect of such active integration with congruent information was robust, even with an interference task occurring right after each encoding word list. In addition, via electroencephalography, we show in 2 separate studies that the onset of the neural signals of successful encoding appeared early (∼400 ms) during the encoding of congruent words. That the neural signals of successful encoding of congruent and incongruent information followed similarly ∼200 ms later suggests that this earlier neural response contributed to memory formation. We propose that the encoding of events that are congruent with readily available contextual semantics can trigger an accelerated onset of the neural mechanisms, supporting the integration of semantic information with the event input. This faster onset would result in a long-lasting and meaningful memory trace for the event but, at the same time, make it difficult to distinguish it from plausible but never encoded events (i.e., related false memories). Conceptual or schema congruence has a strong influence on long-term memory. However, the question of whether schema-related integration neural mechanisms occur during online encoding has yet to be clarified. We investigated the neural mechanisms reflecting how the active

Asymmetric synthesis using chiral-encoded metal

Science.gov (United States)

Yutthalekha, Thittaya; Wattanakit, Chularat; Lapeyre, Veronique; Nokbin, Somkiat; Warakulwit, Chompunuch; Limtrakul, Jumras; Kuhn, Alexander

2016-08-01

The synthesis of chiral compounds is of crucial importance in many areas of society and science, including medicine, biology, chemistry, biotechnology and agriculture. Thus, there is a fundamental interest in developing new approaches for the selective production of enantiomers. Here we report the use of mesoporous metal structures with encoded geometric chiral information for inducing asymmetry in the electrochemical synthesis of mandelic acid as a model molecule. The chiral-encoded mesoporous metal, obtained by the electrochemical reduction of platinum salts in the presence of a liquid crystal phase and the chiral template molecule, perfectly retains the chiral information after removal of the template. Starting from a prochiral compound we demonstrate enantiomeric excess of the (R)-enantiomer when using (R)-imprinted electrodes and vice versa for the (S)-imprinted ones. Moreover, changing the amount of chiral cavities in the material allows tuning the enantioselectivity.

Physical exercise during encoding improves vocabulary learning in young female adults: a neuroendocrinological study.

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Schmidt-Kassow, Maren; Deusser, Marie; Thiel, Christian; Otterbein, Sascha; Montag, Christian; Reuter, Martin; Banzer, Winfried; Kaiser, Jochen

2013-01-01

Acute physical activity has been repeatedly shown to improve various cognitive functions. However, there have been no investigations comparing the effects of exercise during verbal encoding versus exercise prior to encoding on long-term memory performance. In this current psychoneuroendocrinological study we aim to test whether light to moderate ergometric bicycling during vocabulary encoding enhances subsequent recall compared to encoding during physical rest and encoding after being physically active. Furthermore, we examined the kinetics of brain-derived neurotrophic factor (BDNF) in serum which has been previously shown to correlate with learning performance. We also controlled for the BDNF val66met polymorphism. We found better vocabulary test performance for subjects that were physically active during the encoding phase compared to sedentary subjects. Post-hoc tests revealed that this effect was particularly present in initially low performers. BDNF in serum and BDNF genotype failed to account for the current result. Our data indicates that light to moderate simultaneous physical activity during encoding, but not prior to encoding, is beneficial for subsequent recall of new items.

Low-dose Propofol–induced Amnesia Is Not due to a Failure of Encoding

OpenAIRE

Veselis, Robert A.; Pryor, Kane O.; Reinsel, Ruth A.; Mehta, Meghana; Pan, Hong; Johnson, Ray

2008-01-01

Background—Propofol may produce amnesia by affecting encoding. The hypothesis that propofol weakens encoding was tested by measuring regional cerebral blood flow during verbal encoding. Methods—17 volunteer participants (12 M, 30.4±6.5 years old) had regional cerebral blood flow measured using H2O15 positron emission tomography during complex and simple encoding tasks (deep vs. shallow level of processing), to identify a region of interest in the left inferior prefrontal cortex...

The Contribution of Encoding and Retrieval Processes to Proactive Interference

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Kliegl, Oliver; Pastötter, Bernhard; Bäuml, Karl-Heinz T.

2015-01-01

Proactive interference (PI) refers to the finding that memory for recently studied (target) material can be impaired by the prior study of other (nontarget) material. Previous accounts of PI differed in whether they attributed PI to impaired retrieval or impaired encoding. Here, we suggest an integrated encoding-retrieval account, which assigns a…

Yeast PAH1-encoded phosphatidate phosphatase controls the expression of CHO1-encoded phosphatidylserine synthase for membrane phospholipid synthesis.

Science.gov (United States)

Han, Gil-Soo; Carman, George M

2017-08-11

The PAH1 -encoded phosphatidate phosphatase (PAP), which catalyzes the committed step for the synthesis of triacylglycerol in Saccharomyces cerevisiae , exerts a negative regulatory effect on the level of phosphatidate used for the de novo synthesis of membrane phospholipids. This raises the question whether PAP thereby affects the expression and activity of enzymes involved in phospholipid synthesis. Here, we examined the PAP-mediated regulation of CHO1 -encoded phosphatidylserine synthase (PSS), which catalyzes the committed step for the synthesis of major phospholipids via the CDP-diacylglycerol pathway. The lack of PAP in the pah1 Δ mutant highly elevated PSS activity, exhibiting a growth-dependent up-regulation from the exponential to the stationary phase of growth. Immunoblot analysis showed that the elevation of PSS activity results from an increase in the level of the enzyme encoded by CHO1 Truncation analysis and site-directed mutagenesis of the CHO1 promoter indicated that Cho1 expression in the pah1 Δ mutant is induced through the inositol-sensitive upstream activation sequence (UAS INO ), a cis -acting element for the phosphatidate-controlled Henry (Ino2-Ino4/Opi1) regulatory circuit. The abrogation of Cho1 induction and PSS activity by a CHO1 UAS INO mutation suppressed pah1 Δ effects on lipid synthesis, nuclear/endoplasmic reticulum membrane morphology, and lipid droplet formation, but not on growth at elevated temperature. Loss of the DGK1 -encoded diacylglycerol kinase, which converts diacylglycerol to phosphatidate, partially suppressed the pah1 Δ-mediated induction of Cho1 and PSS activity. Collectively, these data showed that PAP activity controls the expression of PSS for membrane phospholipid synthesis. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Identification and validation of human papillomavirus encoded microRNAs.

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Kui Qian

Full Text Available We report here identification and validation of the first papillomavirus encoded microRNAs expressed in human cervical lesions and cell lines. We established small RNA libraries from ten human papillomavirus associated cervical lesions including cancer and two human papillomavirus harboring cell lines. These libraries were sequenced using SOLiD 4 technology. We used the sequencing data to predict putative viral microRNAs and discovered nine putative papillomavirus encoded microRNAs. Validation was performed for five candidates, four of which were successfully validated by qPCR from cervical tissue samples and cell lines: two were encoded by HPV 16, one by HPV 38 and one by HPV 68. The expression of HPV 16 microRNAs was further confirmed by in situ hybridization, and colocalization with p16INK4A was established. Prediction of cellular target genes of HPV 16 encoded microRNAs suggests that they may play a role in cell cycle, immune functions, cell adhesion and migration, development, and cancer. Two putative viral target sites for the two validated HPV 16 miRNAs were mapped to the E5 gene, one in the E1 gene, two in the L1 gene and one in the LCR region. This is the first report to show that papillomaviruses encode their own microRNA species. Importantly, microRNAs were found in libraries established from human cervical disease and carcinoma cell lines, and their expression was confirmed in additional tissue samples. To our knowledge, this is also the first paper to use in situ hybridization to show the expression of a viral microRNA in human tissue.

Encoding color information for visual tracking: Algorithms and benchmark.

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Liang, Pengpeng; Blasch, Erik; Ling, Haibin

2015-12-01

While color information is known to provide rich discriminative clues for visual inference, most modern visual trackers limit themselves to the grayscale realm. Despite recent efforts to integrate color in tracking, there is a lack of comprehensive understanding of the role color information can play. In this paper, we attack this problem by conducting a systematic study from both the algorithm and benchmark perspectives. On the algorithm side, we comprehensively encode 10 chromatic models into 16 carefully selected state-of-the-art visual trackers. On the benchmark side, we compile a large set of 128 color sequences with ground truth and challenge factor annotations (e.g., occlusion). A thorough evaluation is conducted by running all the color-encoded trackers, together with two recently proposed color trackers. A further validation is conducted on an RGBD tracking benchmark. The results clearly show the benefit of encoding color information for tracking. We also perform detailed analysis on several issues, including the behavior of various combinations between color model and visual tracker, the degree of difficulty of each sequence for tracking, and how different challenge factors affect the tracking performance. We expect the study to provide the guidance, motivation, and benchmark for future work on encoding color in visual tracking.

Neutral details associated with emotional events are encoded: evidence from a cued recall paradigm.

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Mickley Steinmetz, Katherine R; Knight, Aubrey G; Kensinger, Elizabeth A

2016-11-01

Enhanced emotional memory often comes at the cost of memory for surrounding background information. Narrowed-encoding theories suggest that this is due to narrowed attention for emotional information at encoding, leading to impaired encoding of background information. Recent work has suggested that an encoding-based theory may be insufficient. Here, we examined whether cued recall-instead of previously used recognition memory tasks-would reveal evidence that non-emotional information associated with emotional information was effectively encoded. Participants encoded positive, negative, or neutral objects on neutral backgrounds. At retrieval, they were given either the item or the background as a memory cue and were asked to recall the associated scene element. Counter to narrowed-encoding theories, emotional items were more likely than neutral items to trigger recall of the associated background. This finding suggests that there is a memory trace of this contextual information and that emotional cues may facilitate retrieval of this information.

Encoding, storage and judgment of experienced frequency and duration

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Tilmann Betsch

2010-08-01

Full Text Available This paper examines conditions that do or do not lead to accurate judgments of frequency (JOF and judgments of duration (JOD. In three experiments, duration and frequency of visually presented stimuli are varied orthogonally in a within-subjects design. Experiment 1 reveals an asymmetric judgment pattern. JOFs reflected actual presentation frequency quite accurately and were unbiased by exposure duration. Conversely, JODs were almost insensitive to actual exposure duration and were systematically biased by presentation frequency. We show, however, that a tendency towards a symmetric judgment pattern can be obtained by manipulating encoding conditions. Sustaining attention during encoding (Experiment 2 or enhancing richness of the encoded stimuli (Experiment 3 increases judgment sensitivity in JOD and yields biases in both directions (JOF biased by exposure duration, JOD biased by presentation frequency. The implications of these findings for underlying memory mechanisms are discussed.

Effects of deoxycycline induced lentivirus encoding FasL gene on ...

African Journals Online (AJOL)

Abstract. Fas/Fas ligand (FasL)-mediated apoptosis plays a critical role in deletion of activated T cells. This study aimed to construct the lentivirus encoding FasL gene induced by deoxycycline and evaluate its effects on apoptosis of Th1 cells. A plasmid expression system encoding FasL was constructed through utilizing the ...

ENCODE: A Sourcebook of Epigenomes and Chromatin Language

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Maryam Yavartanoo

2013-03-01

Full Text Available Until recently, since the Human Genome Project, the general view has been that the majority of the human genome is composed of junk DNA and has little or no selective advantage to the organism. Now we know that this conclusion is an oversimplification. In April 2003, the National Human Genome Research Institute (NHGRI launched an international research consortium called Encyclopedia of DNA Elements (ENCODE to uncover non-coding functional elements in the human genome. The result of this project has identified a set of new DNA regulatory elements, based on novel relationships among chromatin accessibility, histone modifications, nucleosome positioning, DNA methylation, transcription, and the occupancy of sequence-specific factors. The project gives us new insights into the organization and regulation of the human genome and epigenome. Here, we sought to summarize particular aspects of the ENCODE project and highlight the features and data that have recently been released. At the end of this review, we have summarized a case study we conducted using the ENCODE epigenome data.

DNA-Encoded Dynamic Combinatorial Chemical Libraries.

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Reddavide, Francesco V; Lin, Weilin; Lehnert, Sarah; Zhang, Yixin

2015-06-26

Dynamic combinatorial chemistry (DCC) explores the thermodynamic equilibrium of reversible reactions. Its application in the discovery of protein binders is largely limited by difficulties in the analysis of complex reaction mixtures. DNA-encoded chemical library (DECL) technology allows the selection of binders from a mixture of up to billions of different compounds; however, experimental results often show low a signal-to-noise ratio and poor correlation between enrichment factor and binding affinity. Herein we describe the design and application of DNA-encoded dynamic combinatorial chemical libraries (EDCCLs). Our experiments have shown that the EDCCL approach can be used not only to convert monovalent binders into high-affinity bivalent binders, but also to cause remarkably enhanced enrichment of potent bivalent binders by driving their in situ synthesis. We also demonstrate the application of EDCCLs in DNA-templated chemical reactions. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Encoding of QC-LDPC Codes of Rank Deficient Parity Matrix

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Mohammed Kasim Mohammed Al-Haddad

2016-05-01

Full Text Available the encoding of long low density parity check (LDPC codes presents a challenge compared to its decoding. The Quasi Cyclic (QC LDPC codes offer the advantage for reducing the complexity for both encoding and decoding due to its QC structure. Most QC-LDPC codes have rank deficient parity matrix and this introduces extra complexity over the codes with full rank parity matrix. In this paper an encoding scheme of QC-LDPC codes is presented that is suitable for codes with full rank parity matrix and rank deficient parity matrx. The extra effort required by the codes with rank deficient parity matrix over the codes of full rank parity matrix is investigated.

The influence of encoding strategy on episodic memory and cortical activity in schizophrenia.

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Bonner-Jackson, Aaron; Haut, Kristen; Csernansky, John G; Barch, Deanna M

2005-07-01

Recent work suggests that episodic memory deficits in schizophrenia may be related to disturbances of encoding or retrieval. Schizophrenia patients appear to benefit from instruction in episodic memory strategies. We tested the hypothesis that providing effective encoding strategies to schizophrenia patients enhances encoding-related brain activity and recognition performance. Seventeen schizophrenia patients and 26 healthy comparison subjects underwent functional magnetic resonance imaging scans while performing incidental encoding tasks of words and faces. Subjects were required to make either deep (abstract/concrete) or shallow (alphabetization) judgments for words and deep (gender) judgments for faces, followed by subsequent recognition tests. Schizophrenia and comparison subjects recognized significantly more words encoded deeply than shallowly, activated regions in inferior frontal cortex (Brodmann area 45/47) typically associated with deep and successful encoding of words, and showed greater left frontal activation for the processing of words compared with faces. However, during deep encoding and material-specific processing (words vs. faces), participants with schizophrenia activated regions not activated by control subjects, including several in prefrontal cortex. Our findings suggest that a deficit in use of effective strategies influences episodic memory performance in schizophrenia and that abnormalities in functional brain activation persist even when such strategies are applied.

Encoding circuit for transform coding of a picture signal and decoding circuit for encoding said signal

NARCIS (Netherlands)

1991-01-01

Encoding circuit for transforming a picture signal into blocks of, for example, 8*8 coefficients, in which each block of coefficients is read motion-adaptively. In the case of motion within a sub-picture, the block of coefficients is read in such an order that the obtained series of coefficients

Development and Synthesis of DNA-Encoded Benzimidazole Library.

Science.gov (United States)

Ding, Yun; Chai, Jing; Centrella, Paolo A; Gondo, Chenaimwoyo; DeLorey, Jennifer L; Clark, Matthew A

2018-04-25

Encoded library technology (ELT) is an effective approach to the discovery of novel small-molecule ligands for biological targets. A key factor for the success of the technology is the chemical diversity of the libraries. Here we report the development of DNA-conjugated benzimidazoles. Using 4-fluoro-3-nitrobenzoic acid as a key synthon, we synthesized a 320 million-member DNA-encoded benzimidazole library using Fmoc-protected amino acids, amines and aldehydes as diversity elements. Affinity selection of the library led to the discovery of a novel, potent and specific antagonist of the NK3 receptor.

Non-deterministic quantum CNOT gate with double encoding

Science.gov (United States)

Gueddana, Amor; Attia, Moez; Chatta, Rihab

2013-09-01

We define an Asymmetric Partially Polarizing Beam Splitter (APPBS) to be a linear optical component having different reflectivity (transmittance) coefficients, on the upper and the lower arms, for horizontally and vertically Polarized incident photons. Our CNOT model is composed by two APPBSs, one Half Wave Plate (HWP), two Polarizing Beam Splitters (PBSs), a Beam Splitter (BS) and a -phase rotator for specific wavelength. Control qubit operates with dual rail encoding while target qubit is based on polarization encoding. To perform CNOT operation in 4/27 of the cases, input and target incoming photons are injected with different wavelengths.

Nucleic acid compositions and the encoding proteins

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Preston, III, James F.; Chow, Virginia; Nong, Guang; Rice, John D.; St. John, Franz J.

2014-09-02

The subject invention provides at least one nucleic acid sequence encoding an aldouronate-utilization regulon isolated from Paenibacillus sp. strain JDR-2, a bacterium which efficiently utilizes xylan and metabolizes aldouronates (methylglucuronoxylosaccharides). The subject invention also provides a means for providing a coordinately regulated process in which xylan depolymerization and product assimilation are coupled in Paenibacillus sp. strain JDR-2 to provide a favorable system for the conversion of lignocellulosic biomass to biobased products. Additionally, the nucleic acid sequences encoding the aldouronate-utilization regulon can be used to transform other bacteria to form organisms capable of producing a desired product (e.g., ethanol, 1-butanol, acetoin, 2,3-butanediol, 1,3-propanediol, succinate, lactate, acetate, malate or alanine) from lignocellulosic biomass.

DS-OCDMA Encoder/Decoder Performance Analysis Using Optical Low-Coherence Reflectometry

Science.gov (United States)

Fsaifes, Ihsan; Lepers, Catherine; Obaton, Anne-Francoise; Gallion, Philippe

2006-08-01

Direct-sequence optical code-division multiple-access (DS-OCDMA) encoder/decoder based on sampled fiber Bragg gratings (S-FBGs) is characterized using phase-sensitive optical low-coherence reflectometry (OLCR). The OLCR technique allows localized measurements of FBG wavelength and physical length inside one S-FBG. This paper shows how the discrepancies between specifications and measurements of the different FBGs have some impact on spectral and temporal pulse responses of the OCDMA encoder/decoder. The FBG physical lengths lower than the specified ones are shown to affect the mean optical power reflected by the OCDMA encoder/decoder. The FBG wavelengths that are detuned from each other induce some modulations of S-FBG reflectivity resulting in encoder/decoder sensitivity to laser wavelength drift of the OCDMA system. Finally, highlighted by this OLCR study, some solutions to overcome limitations in performance with the S-FBG technology are suggested.

High-performance fluorescence-encoded magnetic microbeads as microfluidic protein chip supports for AFP detection

Energy Technology Data Exchange (ETDEWEB)

Gong, Xiaoqun [School of Life Sciences, Tianjin Engineering Center of Micro-Nano Biomaterials and Detection-Treatment Technology, Collaborative Innovation Center of Chemical Science and Engineering, Tianjin University, Tianjin 300072 (China); Yan, Huan; Yang, Jiumin [Department of Laboratory Medicine, Tianjin Medical University General Hospital, Tianjin, 300052 (China); Wu, Yudong; Zhang, Jian; Yao, Yingyi [School of Life Sciences, Tianjin Engineering Center of Micro-Nano Biomaterials and Detection-Treatment Technology, Collaborative Innovation Center of Chemical Science and Engineering, Tianjin University, Tianjin 300072 (China); Liu, Ping [Bioscience (Tianjin) Diagnostic Technology CO., LTD, Tianjin, 300300 (China); Wang, Huiquan [Department of Biomedical Engineering, School of Electronics and Information Engineering, Tianjin Polytechnic University, Tianjin, 300387 (China); Hu, Zhidong, E-mail: huzhidong27@163.com [Department of Laboratory Medicine, Tianjin Medical University General Hospital, Tianjin, 300052 (China); Chang, Jin, E-mail: jinchang@tju.edu.cn [School of Life Sciences, Tianjin Engineering Center of Micro-Nano Biomaterials and Detection-Treatment Technology, Collaborative Innovation Center of Chemical Science and Engineering, Tianjin University, Tianjin 300072 (China)

2016-10-05

Fluorescence-encoded magnetic microbeads (FEMMs), with the fluorescence encoding ability of quantum dots (QDs) and magnetic enrichment and separation functions of Fe{sub 3}O{sub 4} nanoparticles, have been widely used for multiple biomolecular detection as microfluidic protein chip supports. However, the preparation of FEMMs with long-term fluorescent encoding and immunodetection stability is still a challenge. In this work, we designed a novel high-temperature chemical swelling strategy. The QDs and Fe{sub 3}O{sub 4} nanoparticles were effectively packaged into microbeads via the thermal motion of the polymer chains and the hydrophobic interaction between the nanoparticles and microbeads. The FEMMs obtained a highly uniform fluorescent property and long-term encoding and immunodetection stability and could be quickly magnetically separated and enriched. Then, the QD-encoded magnetic microbeads were applied to alpha fetoprotein (AFP) detection via sandwich immunoreaction. The properties of the encoded microspheres were characterized using a self-designed detecting apparatus, and the target molecular concentration in the sample was also quantified. The results suggested that the high-performance FEMMs have great potential in the field of biomolecular detection. - Graphical abstract: We designed a novel strategy to prepare a kind of high-performance fluorescence-encoded magnetic microbeads as microfluidic protein chip support with long-time fluorescent encoding and immunodetection stability for AFP detection. - Highlights: • A novel strategy combined the high temperature with chemical swelling technology is designed. • Based on hydrophobic interaction and polymer thermal motion, QDs and Fe{sub 3}O{sub 4} were effectively packaged into microbeads. • The fluorescence-encoded magnetic microbeads show long-term fluorescent encoding and immunodetection stability.

Does long-term object priming depend on the explicit detection of object identity at encoding?

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Carlos Alexandre Gomes

2015-03-01

Full Text Available It is currently unclear whether objects have to be explicitly identified at encoding for reliable behavioural long-term object priming to occur. We conducted two experiments that investigated long-term object and non-object priming using a selective-attention encoding manipulation that reduces explicit object identification. In Experiment 1, participants either counted dots flashed within an object picture (shallow encoding or engaged in an animacy task (deep encoding at study, whereas, at test, they performed an object-decision task. Priming, as measured by reaction times, was observed for both types of encoding, and was of equivalent magnitude. In Experiment 2, non-object priming (faster reaction times for studied relative to unstudied non-objects was also obtained under the same selective-attention encoding manipulation as in Experiment 1, and the magnitude of the priming effect was equivalent between experiments. In contrast, we observed a linear decrement in recognition memory accuracy across conditions (deep encoding of Experiment 1 > shallow encoding Experiment 1 > shallow encoding of Experiment 2, suggesting that priming was not contaminated by explicit memory strategies. We argue that our results are more consistent with the identification/production framework than the perceptual/conceptual distinction, and we conclude that priming of pictures largely ignored at encoding can be subserved by the automatic retrieval of two types of instances: one at the motor-level and another at an object-decision level.

Genome-wide identification of structural variants in genes encoding drug targets

DEFF Research Database (Denmark)

Rasmussen, Henrik Berg; Dahmcke, Christina Mackeprang

2012-01-01

The objective of the present study was to identify structural variants of drug target-encoding genes on a genome-wide scale. We also aimed at identifying drugs that are potentially amenable for individualization of treatments based on knowledge about structural variation in the genes encoding...

Processing and display of three-dimensional arrays of numerical data using octree encoding

International Nuclear Information System (INIS)

Amans, J.L.; Antoine, M.; Darier, P.

1986-04-01

The analysis of three-dimensional (3-D) arrays of numerical data from medical, industrial or scientific imaging, by synthetic generation of realistic images, has been widely developed. The Octree encoding, that organizes the volume data in a hierarchical tree structure, has some interesting features for 3-D arrays of data processing. The Octree encoding method, based on the recursive subdivision of a 3-D array, is an extension of the Quadtree encoding in the two-dimensional plane. We have developed a software package to validate the basic Octree encoding methodology for some manipulation and display operations of volume data. The contribution introduces the technique we have used (called ''overlay technique'') to make the projection operation of an Octree on a Quadtree encoded image plane. The application of this technique to the hidden surface display is presented [fr

Genome-wide comparative analysis of NBS-encoding genes between Brassica species and Arabidopsis thaliana.

Science.gov (United States)

Yu, Jingyin; Tehrim, Sadia; Zhang, Fengqi; Tong, Chaobo; Huang, Junyan; Cheng, Xiaohui; Dong, Caihua; Zhou, Yanqiu; Qin, Rui; Hua, Wei; Liu, Shengyi

2014-01-03

Plant disease resistance (R) genes with the nucleotide binding site (NBS) play an important role in offering resistance to pathogens. The availability of complete genome sequences of Brassica oleracea and Brassica rapa provides an important opportunity for researchers to identify and characterize NBS-encoding R genes in Brassica species and to compare with analogues in Arabidopsis thaliana based on a comparative genomics approach. However, little is known about the evolutionary fate of NBS-encoding genes in the Brassica lineage after split from A. thaliana. Here we present genome-wide analysis of NBS-encoding genes in B. oleracea, B. rapa and A. thaliana. Through the employment of HMM search and manual curation, we identified 157, 206 and 167 NBS-encoding genes in B. oleracea, B. rapa and A. thaliana genomes, respectively. Phylogenetic analysis among 3 species classified NBS-encoding genes into 6 subgroups. Tandem duplication and whole genome triplication (WGT) analyses revealed that after WGT of the Brassica ancestor, NBS-encoding homologous gene pairs on triplicated regions in Brassica ancestor were deleted or lost quickly, but NBS-encoding genes in Brassica species experienced species-specific gene amplification by tandem duplication after divergence of B. rapa and B. oleracea. Expression profiling of NBS-encoding orthologous gene pairs indicated the differential expression pattern of retained orthologous gene copies in B. oleracea and B. rapa. Furthermore, evolutionary analysis of CNL type NBS-encoding orthologous gene pairs among 3 species suggested that orthologous genes in B. rapa species have undergone stronger negative selection than those in B .oleracea species. But for TNL type, there are no significant differences in the orthologous gene pairs between the two species. This study is first identification and characterization of NBS-encoding genes in B. rapa and B. oleracea based on whole genome sequences. Through tandem duplication and whole genome

A fast improved fat tree encoder for wave union TDC in an FPGA

International Nuclear Information System (INIS)

Shen Qi; Zhao Lei; Liu Shubin; Qi Binxiang; Hu Xueye; An Qi; Liao Shengkai; Peng Chengzhi

2013-01-01

Up to now, the wave union method can achieve the best timing performance in FPGA-based TDC designs. However, it should be guaranteed in such a structure that the non-thermometer code to binary code (NTH2B) encoding process should be finished within just one system clock cycle. So the implementation of the NTH2B encoder is quite challenging considering the high speed requirement. Besides, the high resolution wave union TDC also demands that the encoder convert an ultra-wide input code to a binary code. We present a fast improved fat tree encoder (IFTE) to fulfill such requirements, in which bubble error suppression is also integrated. With this encoder scheme, a wave union TDC with 7.7 ps RMS and 3.8 ps effective bin size was implemented in an FPGA from Xilinx Virtex 5 family. An encoding time of 8.33 ns was achieved for a 276-bit non-thermometer code to a 9-bit binary code conversion. We conducted a series of tests on the oscillating period of the wave union launcher, as well as the overall performance of the TDC; test results indicate that the IFTE works well. In fact, in the implementation of this encoder, no manual routing or special constraints were required; therefore, this IFTE structure could also be further applied in other delay-chain-based FPGA TDCs. (authors)

A flow cytometric assay technology based on quantum dots-encoded beads

International Nuclear Information System (INIS)

Wang Haiqiao; Liu Tiancai; Cao Yuancheng; Huang Zhenli; Wang Jianhao; Li Xiuqing; Zhao Yuandi

2006-01-01

A flow cytometric detecting technology based on quantum dots (QDs)-encoded beads has been described. Using this technology, several QDs-encoded beads with different code were identified effectively, and the target molecule (DNA sequence) in solution was also detected accurately by coupling to its complementary sequence probed on QDs-encoded beads through DNA hybridization assay. The resolution of this technology for encoded beads is resulted from two longer wavelength fluorescence identification signals (yellow and red fluorescent signals of QDs), and the third shorter wavelength fluorescence signal (green reporting signal of fluorescein isothiocyanate (FITC)) for the determination of reaction between probe and target. In experiment, because of QDs' unique optical character, only one excitation light source was needed to excite the QDs and probe dye FITC synchronously comparing with other flow cytometric assay technology. The results show that this technology has present excellent repeatability and good accuracy. It will become a promising multiple assay platform in various application fields after further improvement

Security of BB84 with weak randomness and imperfect qubit encoding

Science.gov (United States)

Zhao, Liang-Yuan; Yin, Zhen-Qiang; Li, Hong-Wei; Chen, Wei; Fang, Xi; Han, Zheng-Fu; Huang, Wei

2018-03-01

The main threats for the well-known Bennett-Brassard 1984 (BB84) practical quantum key distribution (QKD) systems are that its encoding is inaccurate and measurement device may be vulnerable to particular attacks. Thus, a general physical model or security proof to tackle these loopholes simultaneously and quantitatively is highly desired. Here we give a framework on the security of BB84 when imperfect qubit encoding and vulnerability of measurement device are both considered. In our analysis, the potential attacks to measurement device are generalized by the recently proposed weak randomness model which assumes the input random numbers are partially biased depending on a hidden variable planted by an eavesdropper. And the inevitable encoding inaccuracy is also introduced here. From a fundamental view, our work reveals the potential information leakage due to encoding inaccuracy and weak randomness input. For applications, our result can be viewed as a useful tool to quantitatively evaluate the security of a practical QKD system.

Recognition memory is improved by a structured temporal framework during encoding

Directory of Open Access Journals (Sweden)

Sathesan eThavabalasingam

2016-01-01

Full Text Available In order to function optimally within our environment, we continuously extract temporal patterns from our experiences and formulate expectations that facilitate adaptive behavior. Given that our memories are embedded within spatiotemporal contexts, an intriguing possibility is that mnemonic processes are sensitive to the temporal structure of events. To test this hypothesis, in a series of behavioral experiments we manipulated the regularity of interval durations at encoding to create temporally structured and unstructured frameworks. Our findings revealed enhanced recognition memory (d’ for stimuli that were explicitly encoded within a temporally structured versus unstructured framework. Encoding information within a temporally structured framework was also associated with a reduction in the negative effects of proactive interference and was linked to greater recollective recognition memory. Furthermore, rhythmic temporal structure was found to enhance recognition memory for incidentally encoded information. Collectively, these results support the possibility that we possess a greater capacity to learn and subsequently remember temporally structured information.

47 CFR 11.32 - EAS Encoder.

Science.gov (United States)

2010-10-01

... Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL EMERGENCY ALERT SYSTEM (EAS) Equipment Requirements § 11... operation. (vi) Indicator Display. The encoder shall be provided with a visual and/or aural indicator which... to +50 degrees C and a range of relative humidity of up to 95%. (c) Primary Supply Voltage Variation...

Holovideo: Real-time 3D range video encoding and decoding on GPU

Science.gov (United States)

Karpinsky, Nikolaus; Zhang, Song

2012-02-01

We present a 3D video-encoding technique called Holovideo that is capable of encoding high-resolution 3D videos into standard 2D videos, and then decoding the 2D videos back into 3D rapidly without significant loss of quality. Due to the nature of the algorithm, 2D video compression such as JPEG encoding with QuickTime Run Length Encoding (QTRLE) can be applied with little quality loss, resulting in an effective way to store 3D video at very small file sizes. We found that under a compression ratio of 134:1, Holovideo to OBJ file format, the 3D geometry quality drops at a negligible level. Several sets of 3D videos were captured using a structured light scanner, compressed using the Holovideo codec, and then uncompressed and displayed to demonstrate the effectiveness of the codec. With the use of OpenGL Shaders (GLSL), the 3D video codec can encode and decode in realtime. We demonstrated that for a video size of 512×512, the decoding speed is 28 frames per second (FPS) with a laptop computer using an embedded NVIDIA GeForce 9400 m graphics processing unit (GPU). Encoding can be done with this same setup at 18 FPS, making this technology suitable for applications such as interactive 3D video games and 3D video conferencing.

Comparison between different encoding schemes for synthetic aperture imaging

DEFF Research Database (Denmark)

Nikolov, Svetoslav; Jensen, Jørgen Arendt

2002-01-01

and spatio-temporal encoding was investigated. Experiments on wire phantom in water were carried out to quantify the gain from the different encodings. The gain in SNR using an FM modulated pulse is 12 dB. The penetration depth of the images was studied using tissue mimicking phantom with frequency dependent......Synthetic transmit aperture ultrasound (STAU) imaging can create images with as low as 2 emissions, making it attractive for 3D real-time imaging. Two are the major problems to be solved: (1) complexity of the hardware involved, and (2) poor image quality due to low signal to noise ratio (SNR). We...... attenuation of 0.5 dB/(cm MHz). The combination of spatial and temporal encoding have highest penetration depth. Images to a depth of 110 mm, can successfully be made with contrast resolution comparable to that of a linear array image. The in-vivo scans show that the motion artifacts do not significantly...

Identification of a Novel UTY‐Encoded Minor Histocompatibility Antigen

DEFF Research Database (Denmark)

Mortensen, B. K.; Rasmussen, A. H.; Larsen, Malene Erup

2012-01-01

Minor histocompatibility antigens (mHags) encoded by the Y‐chromosome (H‐Y‐mHags) are known to play a pivotal role in allogeneic haematopoietic cell transplantation (HCT) involving female donors and male recipients. We present a new H‐Y‐mHag, YYNAFHWAI (UTY139–147), encoded by the UTY gene...... obtained post‐HCT from male recipients of female donor grafts. In one of these recipients, a CD8+ T cell response was observed against a peptide stretch encoded by the UTY gene. Another bioinformatics tool, HLArestrictor, was used to identify the optimal peptide and HLA‐restriction element. Using peptide....../HLA tetramers, the specificity of the CD8+ T cell response was successfully validated as being HLA‐A*24:02‐restricted and directed against the male UTY139–147 peptide. Functional analysis of these T cells demonstrated male UTY139–147 peptide‐specific cytokine secretion (IFNγ, TNFα and MIP‐1β) and cytotoxic...

Pareto-optimal multi-objective dimensionality reduction deep auto-encoder for mammography classification.

Science.gov (United States)

Taghanaki, Saeid Asgari; Kawahara, Jeremy; Miles, Brandon; Hamarneh, Ghassan

2017-07-01

Feature reduction is an essential stage in computer aided breast cancer diagnosis systems. Multilayer neural networks can be trained to extract relevant features by encoding high-dimensional data into low-dimensional codes. Optimizing traditional auto-encoders works well only if the initial weights are close to a proper solution. They are also trained to only reduce the mean squared reconstruction error (MRE) between the encoder inputs and the decoder outputs, but do not address the classification error. The goal of the current work is to test the hypothesis that extending traditional auto-encoders (which only minimize reconstruction error) to multi-objective optimization for finding Pareto-optimal solutions provides more discriminative features that will improve classification performance when compared to single-objective and other multi-objective approaches (i.e. scalarized and sequential). In this paper, we introduce a novel multi-objective optimization of deep auto-encoder networks, in which the auto-encoder optimizes two objectives: MRE and mean classification error (MCE) for Pareto-optimal solutions, rather than just MRE. These two objectives are optimized simultaneously by a non-dominated sorting genetic algorithm. We tested our method on 949 X-ray mammograms categorized into 12 classes. The results show that the features identified by the proposed algorithm allow a classification accuracy of up to 98.45%, demonstrating favourable accuracy over the results of state-of-the-art methods reported in the literature. We conclude that adding the classification objective to the traditional auto-encoder objective and optimizing for finding Pareto-optimal solutions, using evolutionary multi-objective optimization, results in producing more discriminative features. Copyright © 2017 Elsevier B.V. All rights reserved.

Distinct Reward Properties are Encoded via Corticostriatal Interactions.

Science.gov (United States)

Smith, David V; Rigney, Anastasia E; Delgado, Mauricio R

2016-02-02

The striatum serves as a critical brain region for reward processing. Yet, understanding the link between striatum and reward presents a challenge because rewards are composed of multiple properties. Notably, affective properties modulate emotion while informative properties help obtain future rewards. We approached this problem by emphasizing affective and informative reward properties within two independent guessing games. We found that both reward properties evoked activation within the nucleus accumbens, a subregion of the striatum. Striatal responses to informative, but not affective, reward properties predicted subsequent utilization of information for obtaining monetary reward. We hypothesized that activation of the striatum may be necessary but not sufficient to encode distinct reward properties. To investigate this possibility, we examined whether affective and informative reward properties were differentially encoded in corticostriatal interactions. Strikingly, we found that the striatum exhibited dissociable connectivity patterns with the ventrolateral prefrontal cortex, with increasing connectivity for affective reward properties and decreasing connectivity for informative reward properties. Our results demonstrate that affective and informative reward properties are encoded via corticostriatal interactions. These findings highlight how corticostriatal systems contribute to reward processing, potentially advancing models linking striatal activation to behavior.

Imaging dynamic redox processes with genetically encoded probes.

Science.gov (United States)

Ezeriņa, Daria; Morgan, Bruce; Dick, Tobias P

2014-08-01

Redox signalling plays an important role in many aspects of physiology, including that of the cardiovascular system. Perturbed redox regulation has been associated with numerous pathological conditions; nevertheless, the causal relationships between redox changes and pathology often remain unclear. Redox signalling involves the production of specific redox species at specific times in specific locations. However, until recently, the study of these processes has been impeded by a lack of appropriate tools and methodologies that afford the necessary redox species specificity and spatiotemporal resolution. Recently developed genetically encoded fluorescent redox probes now allow dynamic real-time measurements, of defined redox species, with subcellular compartment resolution, in intact living cells. Here we discuss the available genetically encoded redox probes in terms of their sensitivity and specificity and highlight where uncertainties or controversies currently exist. Furthermore, we outline major goals for future probe development and describe how progress in imaging methodologies will improve our ability to employ genetically encoded redox probes in a wide range of situations. This article is part of a special issue entitled "Redox Signalling in the Cardiovascular System." Copyright © 2014 Elsevier Ltd. All rights reserved.

Electroencephalographic brain dynamics of memory encoding in emotionally arousing context

Directory of Open Access Journals (Sweden)

Carlos Enrique eUribe

2011-06-01

Full Text Available Emotional content/context enhances declarative memory through modulation of encoding and retrieval mechanisms. At encoding, neurophysiological data have consistently demonstrated the subsequent memory effect in theta and gamma oscillations. Yet, the existing studies were focused on the emotional content effect and let the emotional context effect unexplored. We hypothesized that theta and gamma oscillations show higher evoked/induced activity during the encoding of visual stimuli when delivered in an emotionally arousing context. Twenty-five healthy volunteers underwent evoked potentials recordings using a 21 scalp electrodes montage. They attended to an audiovisual test of emotional declarative memory being randomly assigned to either emotionally arousing or neutral context. Visual stimulus presentation was used as the time-locking event. Grand-averages of the evoked potentials and evoked spectral perturbations were calculated for each volunteer. Evoked potentials showed a higher negative deflection from 80 to 140 ms for the emotional condition. Such effect was observed over central, frontal and prefrontal locations bilaterally. Evoked theta power was higher in left parietal, central, frontal and prefrontal electrodes from -50 to 300 ms in the emotional condition. Evoked gamma power was higher in the emotional condition with a spatial distribution that overlapped at some points with the theta topography. The early theta power increase could be related to expectancy induced by auditory information processing that facilitates visual encoding in emotional contexts. Together, our results suggest that declarative memory enhancement for both emotional content and emotional context are supported by similar neural mechanisms at encoding, and offer new evidence about the brain processing of relevant environmental stimuli.

Temporal information encoding in dynamic memristive devices

Energy Technology Data Exchange (ETDEWEB)

Ma, Wen; Chen, Lin; Du, Chao; Lu, Wei D., E-mail: wluee@eecs.umich.edu [Department of Electrical Engineering and Computer Science, University of Michigan, Ann Arbor, Michigan 48109 (United States)

2015-11-09

We show temporal and frequency information can be effectively encoded in memristive devices with inherent short-term dynamics. Ag/Ag{sub 2}S/Pd based memristive devices with low programming voltage (∼100 mV) were fabricated and tested. At weak programming conditions, the devices exhibit inherent decay due to spontaneous diffusion of the Ag atoms. When the devices were subjected to pulse train inputs emulating different spiking patterns, the switching probability distribution function diverges from the standard Poisson distribution and evolves according to the input pattern. The experimentally observed switching probability distributions and the associated cumulative probability functions can be well-explained using a model accounting for the short-term decay effects. Such devices offer an intriguing opportunity to directly encode neural signals for neural information storage and analysis.

Encoding methods for B1+ mapping in parallel transmit systems at ultra high field

Science.gov (United States)

Tse, Desmond H. Y.; Poole, Michael S.; Magill, Arthur W.; Felder, Jörg; Brenner, Daniel; Jon Shah, N.

2014-08-01

Parallel radiofrequency (RF) transmission, either in the form of RF shimming or pulse design, has been proposed as a solution to the B1+ inhomogeneity problem in ultra high field magnetic resonance imaging. As a prerequisite, accurate B1+ maps from each of the available transmit channels are required. In this work, four different encoding methods for B1+ mapping, namely 1-channel-on, all-channels-on-except-1, all-channels-on-1-inverted and Fourier phase encoding, were evaluated using dual refocusing acquisition mode (DREAM) at 9.4 T. Fourier phase encoding was demonstrated in both phantom and in vivo to be the least susceptible to artefacts caused by destructive RF interference at 9.4 T. Unlike the other two interferometric encoding schemes, Fourier phase encoding showed negligible dependency on the initial RF phase setting and therefore no prior B1+ knowledge is required. Fourier phase encoding also provides a flexible way to increase the number of measurements to increase SNR, and to allow further reduction of artefacts by weighted decoding. These advantages of Fourier phase encoding suggest that it is a good choice for B1+ mapping in parallel transmit systems at ultra high field.

Encoding of physics concepts: concreteness and presentation modality reflected by human brain dynamics.

Directory of Open Access Journals (Sweden)

Kevin Lai

Full Text Available Previous research into working memory has focused on activations in different brain areas accompanying either different presentation modalities (verbal vs. non-verbal or concreteness (abstract vs. concrete of non-science concepts. Less research has been conducted investigating how scientific concepts are learned and further processed in working memory. To bridge this gap, the present study investigated human brain dynamics associated with encoding of physics concepts, taking both presentation modality and concreteness into account. Results of this study revealed greater theta and low-beta synchronization in the anterior cingulate cortex (ACC during encoding of concrete pictures as compared to the encoding of both high and low imageable words. In visual brain areas, greater theta activity accompanying stimulus onsets was observed for words as compared to pictures while stronger alpha suppression was observed in responses to pictures as compared to words. In general, the EEG oscillation patterns for encoding words of different levels of abstractness were comparable but differed significantly from encoding of pictures. These results provide insights into the effects of modality of presentation on human encoding of scientific concepts and thus might help in developing new ways to better teach scientific concepts in class.

Encoding of physics concepts: concreteness and presentation modality reflected by human brain dynamics.

Science.gov (United States)

Lai, Kevin; She, Hsiao-Ching; Chen, Sheng-Chang; Chou, Wen-Chi; Huang, Li-Yu; Jung, Tzyy-Ping; Gramann, Klaus

2012-01-01

Previous research into working memory has focused on activations in different brain areas accompanying either different presentation modalities (verbal vs. non-verbal) or concreteness (abstract vs. concrete) of non-science concepts. Less research has been conducted investigating how scientific concepts are learned and further processed in working memory. To bridge this gap, the present study investigated human brain dynamics associated with encoding of physics concepts, taking both presentation modality and concreteness into account. Results of this study revealed greater theta and low-beta synchronization in the anterior cingulate cortex (ACC) during encoding of concrete pictures as compared to the encoding of both high and low imageable words. In visual brain areas, greater theta activity accompanying stimulus onsets was observed for words as compared to pictures while stronger alpha suppression was observed in responses to pictures as compared to words. In general, the EEG oscillation patterns for encoding words of different levels of abstractness were comparable but differed significantly from encoding of pictures. These results provide insights into the effects of modality of presentation on human encoding of scientific concepts and thus might help in developing new ways to better teach scientific concepts in class.

Implementation-intention encoding in a prospective memory task enhances spontaneous retrieval of intentions.

Science.gov (United States)

Rummel, Jan; Einstein, Gilles O; Rampey, Hilary

2012-01-01

Although forming implementation intentions (Gollwitzer, 1999) has been demonstrated to generally improve prospective memory, the underlying cognitive mechanisms are not completely understood. It has been proposed that implementation-intention encoding encourages spontaneous retrieval (McDaniel & Scullin, 2010). Alternatively one could assume the positive effect of implementation-intention encoding is caused by increased or more efficient monitoring for target cues. To test these alternative explanations and to further investigate the cognitive mechanisms underlying implementation-intention benefits, in two experiments participants formed the intention to respond to specific target cues in a lexical decision task with a special key, but then had to suspend this intention during an intervening word-categorisation task. Response times on trials directly following the occurrence of target cues in the intervening task were significantly slower with implementation-intention encoding than with standard encoding, indicating that spontaneous retrieval was increased (Experiment 1). However, when activation of the target cues was controlled for, similar slowing was found with both standard and implementation-intention encoding (Experiment 2). The results imply that implementation-intention encoding as well as increased target-cue activation foster spontaneous retrieval processes.

Encoding qubits into oscillators with atomic ensembles and squeezed light

Science.gov (United States)

Motes, Keith R.; Baragiola, Ben Q.; Gilchrist, Alexei; Menicucci, Nicolas C.

2017-05-01

The Gottesman-Kitaev-Preskill (GKP) encoding of a qubit within an oscillator provides a number of advantages when used in a fault-tolerant architecture for quantum computing, most notably that Gaussian operations suffice to implement all single- and two-qubit Clifford gates. The main drawback of the encoding is that the logical states themselves are challenging to produce. Here we present a method for generating optical GKP-encoded qubits by coupling an atomic ensemble to a squeezed state of light. Particular outcomes of a subsequent spin measurement of the ensemble herald successful generation of the resource state in the optical mode. We analyze the method in terms of the resources required (total spin and amount of squeezing) and the probability of success. We propose a physical implementation using a Faraday-based quantum nondemolition interaction.

Using Social Scientific Criteria to Evaluate Cultural Theories: Encoding/Decoding Evaluated

Directory of Open Access Journals (Sweden)

Evan L. Kropp

2015-12-01

Full Text Available This article transcends the issue of conflicting theoretical schools of thought to formulate a method of social scientific style theory evaluation for cultural studies. It is suggested that positivist social scientific models of theory critique can be used to assess cultural models of communication to determine if they should be classified as theories. A set of evaluation criteria is formulated as a guide and applied to Stuart Hall’s Encoding/Decoding to determine if it is a theory. Conclusions find the sharing of criteria between schools of thought is judicious, Encoding/Decoding fits the established criteria, and Encoding/Decoding should be referred to as a theory.

Single-shot imaging with higher-dimensional encoding using magnetic field monitoring and concomitant field correction.

Science.gov (United States)

Testud, Frederik; Gallichan, Daniel; Layton, Kelvin J; Barmet, Christoph; Welz, Anna M; Dewdney, Andrew; Cocosco, Chris A; Pruessmann, Klaas P; Hennig, Jürgen; Zaitsev, Maxim

2015-03-01

PatLoc (Parallel Imaging Technique using Localized Gradients) accelerates imaging and introduces a resolution variation across the field-of-view. Higher-dimensional encoding employs more spatial encoding magnetic fields (SEMs) than the corresponding image dimensionality requires, e.g. by applying two quadratic and two linear spatial encoding magnetic fields to reconstruct a 2D image. Images acquired with higher-dimensional single-shot trajectories can exhibit strong artifacts and geometric distortions. In this work, the source of these artifacts is analyzed and a reliable correction strategy is derived. A dynamic field camera was built for encoding field calibration. Concomitant fields of linear and nonlinear spatial encoding magnetic fields were analyzed. A combined basis consisting of spherical harmonics and concomitant terms was proposed and used for encoding field calibration and image reconstruction. A good agreement between the analytical solution for the concomitant fields and the magnetic field simulations of the custom-built PatLoc SEM coil was observed. Substantial image quality improvements were obtained using a dynamic field camera for encoding field calibration combined with the proposed combined basis. The importance of trajectory calibration for single-shot higher-dimensional encoding is demonstrated using the combined basis including spherical harmonics and concomitant terms, which treats the concomitant fields as an integral part of the encoding. © 2014 Wiley Periodicals, Inc.

Distributed-phase OCDMA encoder-decoders based on fiber Bragg gratings

OpenAIRE

Zhang, Zhaowei; Tian, C.; Petropoulos, P.; Richardson, D.J.; Ibsen, M.

2007-01-01

We propose and demonstrate new optical code-division multiple-access (OCDMA) encoder-decoders having a continuous phase-distribution. With the same spatial refractive index distribution as the reconfigurable optical phase encoder-decoders, they are inherently suitable for the application in reconfigurable OCDMA systems. Furthermore, compared with conventional discrete-phase devices, they also have additional advantages of being more tolerant to input pulse width and, therefore, have the poten...

Selective Memories: Infants' Encoding Is Enhanced in Selection via Suppression

Science.gov (United States)

Markant, Julie; Amso, Dima

2013-01-01

The present study examined the hypothesis that inhibitory visual selection mechanisms play a vital role in memory by limiting distractor interference during item encoding. In Experiment 1a we used a modified spatial cueing task in which 9-month-old infants encoded multiple category exemplars in the contexts of an attention orienting mechanism…

Alpha Oscillations during Incidental Encoding Predict Subsequent Memory for New "Foil" Information.

Science.gov (United States)

Vogelsang, David A; Gruber, Matthias; Bergström, Zara M; Ranganath, Charan; Simons, Jon S

2018-05-01

People can employ adaptive strategies to increase the likelihood that previously encoded information will be successfully retrieved. One such strategy is to constrain retrieval toward relevant information by reimplementing the neurocognitive processes that were engaged during encoding. Using EEG, we examined the temporal dynamics with which constraining retrieval toward semantic versus nonsemantic information affects the processing of new "foil" information encountered during a memory test. Time-frequency analysis of EEG data acquired during an initial study phase revealed that semantic compared with nonsemantic processing was associated with alpha decreases in a left frontal electrode cluster from around 600 msec after stimulus onset. Successful encoding of semantic versus nonsemantic foils during a subsequent memory test was related to decreases in alpha oscillatory activity in the same left frontal electrode cluster, which emerged relatively late in the trial at around 1000-1600 msec after stimulus onset. Across participants, left frontal alpha power elicited by semantic processing during the study phase correlated significantly with left frontal alpha power associated with semantic foil encoding during the memory test. Furthermore, larger left frontal alpha power decreases elicited by semantic foil encoding during the memory test predicted better subsequent semantic foil recognition in an additional surprise foil memory test, although this effect did not reach significance. These findings indicate that constraining retrieval toward semantic information involves reimplementing semantic encoding operations that are mediated by alpha oscillations and that such reimplementation occurs at a late stage of memory retrieval, perhaps reflecting additional monitoring processes.

Emotional Encoding Context Leads to Memory Bias in Individuals with High Anxiety.

Science.gov (United States)

Lee, Christopher; Fernandes, Myra A

2017-12-27

We investigated whether anxious individuals, who adopt an inherently negative mindset, demonstrate a particularly salient memory bias for words tainted by negative contexts. To this end, sequentially presented target words, overlayed onto negative or neutral pictures, were studied in separate blocks (within-subjects) using a deep or shallow encoding instruction (between-subjects). Following study, in Test 1, participants completed separate recognition test blocks for the words overlayed onto the negative and the neutral contexts. Following this, in Test 2, participants completed a recognition test for the foils from each Test 1 block. We found a significant three-way interaction on Test 2, such that individuals with high anxiety who initially studied target words using a shallow encoding instruction, demonstrated significantly elevated memory for foils that were contained within the negative Test 1 block. Results show that during retrieval (Test 1), participants re-entered the mode of processing (negative or neutral) engaged at encoding, tainting the encoding of foils with that same mode of processing. The findings suggest that individuals with high relative to low anxiety, adopt a particularly salient negative retrieval mode, and this creates a downstream bias in encoding and subsequent retrieval of otherwise neutral information.

Event-related rTMS at encoding affects differently deep and shallow memory traces.

Science.gov (United States)

Innocenti, Iglis; Giovannelli, Fabio; Cincotta, Massimo; Feurra, Matteo; Polizzotto, Nicola R; Bianco, Giovanni; Cappa, Stefano F; Rossi, Simone

2010-10-15

The "level of processing" effect is a classical finding of the experimental psychology of memory. Actually, the depth of information processing at encoding predicts the accuracy of the subsequent episodic memory performance. When the incoming stimuli are analyzed in terms of their meaning (semantic, or deep, encoding), the memory performance is superior with respect to the case in which the same stimuli are analyzed in terms of their perceptual features (shallow encoding). As suggested by previous neuroimaging studies and by some preliminary findings with transcranial magnetic stimulation (TMS), the left prefrontal cortex may play a role in semantic processing requiring the allocation of working memory resources. However, it still remains unclear whether deep and shallow encoding share or not the same cortical networks, as well as how these networks contribute to the "level of processing" effect. To investigate the brain areas casually involved in this phenomenon, we applied event-related repetitive TMS (rTMS) during deep (semantic) and shallow (perceptual) encoding of words. Retrieval was subsequently tested without rTMS interference. RTMS applied to the left dorsolateral prefrontal cortex (DLPFC) abolished the beneficial effect of deep encoding on memory performance, both in terms of accuracy (decrease) and reaction times (increase). Neither accuracy nor reaction times were instead affected by rTMS to the right DLPFC or to an additional control site excluded by the memory process (vertex). The fact that online measures of semantic processing at encoding were unaffected suggests that the detrimental effect on memory performance for semantically encoded items took place in the subsequent consolidation phase. These results highlight the specific causal role of the left DLPFC among the wide left-lateralized cortical network engaged by long-term memory, suggesting that it probably represents a crucial node responsible for the improved memory performance induced by

Direct Pathogenic Effects of HERV-encoded Proteins

DEFF Research Database (Denmark)

Hansen, Dorte Tranberg; Møller-Larsen, Anné; Petersen, Thor

Background: Multiple sclerosis (MS) is a demyelinating, inflammatory disease of the central nervous system (CNS). MS is mediated by the immune system but the etiology of the disease remains unknown. Retroviral envelope (Env) proteins, encoded by human endogenous retroviruses (HERVs), are expressed...... in increased amounts on B cells from MS patients. Furthermore, the amount of anti-HERV antibodies in serum and cerebrospinal fluid from patients with MS is increased when compared with healthy controls. Aim: The overall aim of this project is to investigate the potential role of HERVs in the development of MS...... and the possible direct pathogenic effects of HERV-encoded Env proteins on the CNS. Methods: Construction and characterization of a panel of recombinant Env-proteins is initiated and their pathogenic potential will be investigated: Fusiogenic potential analyzed by flow cytometry and confocal microscopy. Analysis...

Bacillus caldolyticus prs gene encoding phosphoribosyldiphosphate synthase

DEFF Research Database (Denmark)

Krath, Britta N.; Hove-Jensen, Bjarne

1996-01-01

The prs gene, encoding phosphoribosyl-diphosphate (PRPP) synthase, as well as the flanking DNA sequences were cloned and sequenced from the Gram-positive thermophile, Bacillus caldolyticus. Comparison with the homologous sequences from the mesophile, Bacillus subtilis, revealed a gene (gca......D) encoding N-acetylglucosamine-l-phosphate uridyltransferase upstream of prs, and a gene homologous to ctc downstream of prs. cDNA synthesis with a B. caldolyticus gcaD-prs-ctc-specified mRNA as template, followed by amplification utilising the polymerase chain reaction indicated that the three genes are co......-transcribed. Comparison of amino acid sequences revealed a high similarity among PRPP synthases across a wide phylogenetic range. An E. coli strain harbouring the B. caldolyticus prs gene in a multicopy plasmid produced PRPP synthase activity 33-fold over the activity of a haploid B. caldolyticus strain. B. caldolyticus...

Efficient Text Encryption and Hiding with Double-Random Phase-Encoding

Directory of Open Access Journals (Sweden)

Mohammad S. Alam

2012-10-01

Full Text Available In this paper, a double-random phase-encoding technique-based text encryption and hiding method is proposed. First, the secret text is transformed into a 2-dimensional array and the higher bits of the elements in the transformed array are used to store the bit stream of the secret text, while the lower bits are filled with specific values. Then, the transformed array is encoded with double-random phase-encoding technique. Finally, the encoded array is superimposed on an expanded host image to obtain the image embedded with hidden data. The performance of the proposed technique, including the hiding capacity, the recovery accuracy of the secret text, and the quality of the image embedded with hidden data, is tested via analytical modeling and test data stream. Experimental results show that the secret text can be recovered either accurately or almost accurately, while maintaining the quality of the host image embedded with hidden data by properly selecting the method of transforming the secret text into an array and the superimposition coefficient. By using optical information processing techniques, the proposed method has been found to significantly improve the security of text information transmission, while ensuring hiding capacity at a prescribed level.

Equal Learning Does Not Result in Equal Remembering: The Importance of Post-Encoding Processes

Science.gov (United States)

Bauer, Patricia J.; Guler, O. Evren; Starr, Rebecca M.; Pathman, Thanujeni

2011-01-01

Explanations of variability in long-term recall typically appeal to encoding and/or retrieval processes. However, for well over a century, it has been apparent that for memory traces to be stored successfully, they must undergo a post-encoding process of stabilization and integration. Variability in post-encoding processes is thus a potential…

Encoding mutually unbiased bases in orbital angular momentum for quantum key distribution

CSIR Research Space (South Africa)

Dudley, Angela L

2013-07-01

Full Text Available We encode mutually unbiased bases (MUBs) using the higher-dimensional orbital angular momentum (OAM) degree of freedom associated with optical fields. We illustrate how these states are encoded with the use of a spatial light modulator (SLM). We...

Encoders for block-circulant LDPC codes

Science.gov (United States)

Divsalar, Dariush (Inventor); Abbasfar, Aliazam (Inventor); Jones, Christopher R. (Inventor); Dolinar, Samuel J. (Inventor); Thorpe, Jeremy C. (Inventor); Andrews, Kenneth S. (Inventor); Yao, Kung (Inventor)

2009-01-01

Methods and apparatus to encode message input symbols in accordance with an accumulate-repeat-accumulate code with repetition three or four are disclosed. Block circulant matrices are used. A first method and apparatus make use of the block-circulant structure of the parity check matrix. A second method and apparatus use block-circulant generator matrices.

Fast Coding Unit Encoding Mechanism for Low Complexity Video Coding

OpenAIRE

Gao, Yuan; Liu, Pengyu; Wu, Yueying; Jia, Kebin; Gao, Guandong

2016-01-01

In high efficiency video coding (HEVC), coding tree contributes to excellent compression performance. However, coding tree brings extremely high computational complexity. Innovative works for improving coding tree to further reduce encoding time are stated in this paper. A novel low complexity coding tree mechanism is proposed for HEVC fast coding unit (CU) encoding. Firstly, this paper makes an in-depth study of the relationship among CU distribution, quantization parameter (QP) and content ...

Towards predicting the encoding capability of MR fingerprinting sequences.

Science.gov (United States)

Sommer, K; Amthor, T; Doneva, M; Koken, P; Meineke, J; Börnert, P

2017-09-01

Sequence optimization and appropriate sequence selection is still an unmet need in magnetic resonance fingerprinting (MRF). The main challenge in MRF sequence design is the lack of an appropriate measure of the sequence's encoding capability. To find such a measure, three different candidates for judging the encoding capability have been investigated: local and global dot-product-based measures judging dictionary entry similarity as well as a Monte Carlo method that evaluates the noise propagation properties of an MRF sequence. Consistency of these measures for different sequence lengths as well as the capability to predict actual sequence performance in both phantom and in vivo measurements was analyzed. While the dot-product-based measures yielded inconsistent results for different sequence lengths, the Monte Carlo method was in a good agreement with phantom experiments. In particular, the Monte Carlo method could accurately predict the performance of different flip angle patterns in actual measurements. The proposed Monte Carlo method provides an appropriate measure of MRF sequence encoding capability and may be used for sequence optimization. Copyright © 2017 Elsevier Inc. All rights reserved.

Lateral and medial prefrontal contributions to emotion generation by semantic elaboration during episodic encoding.

Science.gov (United States)

Kaneda, Takumi; Shigemune, Yayoi; Tsukiura, Takashi

2017-02-01

Memories for emotion-laden stimuli are remembered more accurately than those for neutral stimuli. Although this enhancement reflects stimulus-driven modulation of memory by emotions, functional neuroimaging evidence of the interacting mechanisms between emotions generated by intentional processes, such as semantic elaboration, and memory is scarce. The present fMRI study investigated how encoding-related activation is modulated by emotions generated during the process of semantic elaboration. During encoding with fMRI, healthy young adults viewed neutral (target) pictures either passively or with semantic elaboration. In semantic elaboration, participants imagined background stories related to the pictures. Encoding trials with semantic elaboration were subdivided into conditions in which participants imagined negative, positive, or neutral stories. One week later, memories for target pictures were tested. In behavioral results, memories for target pictures were significantly enhanced by semantic elaboration, compared to passive viewing, and the memory enhancement was more remarkable when negative or positive stories were imagined. fMRI results demonstrated that activations in the left inferior frontal gyrus and dorsal medial prefrontal cortex (dmPFC) were greater during the encoding of target pictures with semantic elaboration than those with passive viewing, and that these activations further increased during encoding with semantic elaboration of emotional stories than of neutral stories. Functional connectivity between the left inferior frontal gyrus and dmPFC/hippocampus during encoding significantly predicted retrieval accuracies of memories encoded with self-generated emotional stories. These findings suggest that networks including the left inferior frontal region, dmPFC, and hippocampus could contribute to the modulation of memories encoded with the emotion generation.

Effect of post-encoding emotion on recollection and familiarity for pictures.

Science.gov (United States)

Wang, Bo; Ren, Yanju

2017-07-01

Although prior studies have examined the effect of post-encoding emotional arousal on recognition memory for words, it is unknown whether the enhancement effect observed on words generalizes to pictures. Furthermore, prior studies using words have showed that the effect of emotional arousal can be modulated by stimuli valence and delay in emotion induction, but it is unclear whether such modulation can extend to pictures and whether other factors such as encoding method (incidental vs. intentional encoding) can be modulatory. Five experiments were conducted to answer these questions. In Experiment 1, participants encoded a list of neutral and negative pictures and then watched a 3-min neutral or negative video. The delayed test showed that negative arousal impaired recollection regardless of picture valence but had no effect on familiarity. Experiment 2 replicated the above findings. Experiment 3 was similar to Experiment 1 except that participants watched a 3-min neutral, negative, or positive video and conducted free recall before the recognition test. Unlike the prior two experiments, the impairment effect of negative arousal disappeared. Experiment 4, where the free recall task was eliminated, replicated the results from Experiment 3. Experiment 5 replicated Experiments 1 and 2 and further showed that the impairment effects of negative arousal could be modulated by delay in emotion induction but not by encoding method or stimuli valence. Taken together, the current study suggests that the enhancement effect observed on words may not generalize to pictures.

A low-latency, low-overhead encoder for data transmission in the ATLAS Liquid Argon Calorimeter trigger upgrade

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Xiao, Le [Department of Physics, Central China Normal University, Wuhan, Hubei 430079 (China); Department of Physics, Southern Methodist University, Dallas, TX 75275 (United States); Li, Xiaoting [Department of Physics, Central China Normal University, Wuhan, Hubei 430079 (China); Gong, Datao, E-mail: dgong@mail.smu.edu [Department of Physics, Southern Methodist University, Dallas, TX 75275 (United States); Chen, Jinghong [Department of Electrical and Computer Engineering, University of Houston, Houston, TX 77004 (United States); Deng, Binwei [School of Electric and Electronic Information Engineering, Hubei Polytechnic University, Huangshi, Hubei 435003 (China); Fan, Qingjun; Feng, Yulang [Department of Electrical and Computer Engineering, University of Houston, Houston, TX 77004 (United States); Guo, Di [Department of Physics, Southern Methodist University, Dallas, TX 75275 (United States); State Key Laboratory of Particle Detection and Electronics, University of Science and Technology of China, Hefei, Anhui 230026 (China); He, Huiqin [Department of Physics, Central China Normal University, Wuhan, Hubei 430079 (China); Department of Physics, Southern Methodist University, Dallas, TX 75275 (United States); Shenzhen Polytechnic, Shenzhen 518055 (China); Hou, Suen [Institute of Physics, Academia Sinica, Nangang 11529, Taipei, Taiwan (China); Huang, Guangming, E-mail: gmhuang@phy.ccnu.edu.cn [Department of Physics, Central China Normal University, Wuhan, Hubei 430079 (China); Liu, Chonghan; Liu, Tiankuan [Department of Physics, Southern Methodist University, Dallas, TX 75275 (United States); Sun, Xiangming [Department of Physics, Central China Normal University, Wuhan, Hubei 430079 (China); Tang, Yuxuan [Department of Electrical and Computer Engineering, University of Houston, Houston, TX 77004 (United States); Teng, Ping-Kun [Institute of Physics, Academia Sinica, Nangang 11529, Taipei, Taiwan (China); and others

2016-09-21

In this paper, we present the design and test results of an encoder integrated circuit for the ATLAS Liquid Argon Calorimeter trigger upgrade. The encoder implements a low-latency and low-overhead line code called LOCic. The encoder operates at 320 MHz with a latency of no greater than 21 ns. The overhead of the encoder is 14.3%. The encoder is an important block of the transmitter ASIC LOCx2, which is prototyped with a commercial 0.25 μm Silicon-on-Sapphire CMOS technology and packaged in a 100-pin QFN package. - Highlights: • We present the design and test results of an encoder integrated circuit for the ATLAS Liquid Argon Calorimeter trigger upgrade. • The encoder implements a low-latency and low-overhead line code called LOCic. The encoder operates at 320 MHz with a latency of no greater than 21 ns. The overhead of the encoder is 14.3%. • The encoder is an important block of the transmitter ASIC LOCx2, which is prototyped with a commercial 0.25 μm Silicon-on-Sapphire CMOS technology for radiation-tolerance and packaged in a 100-pin QFN package.

Determining the Neural Substrate for Encoding a Memory of Human Pain and the Influence of Anxiety.

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Tseng, Ming-Tsung; Kong, Yazhuo; Eippert, Falk; Tracey, Irene

2017-12-06

To convert a painful stimulus into a briefly maintainable construct when the painful stimulus is no longer accessible is essential to guide human behavior and avoid dangerous situations. Because of the aversive nature of pain, this encoding process might be influenced by emotional aspects and could thus vary across individuals, but we have yet to understand both the basic underlying neural mechanisms as well as potential interindividual differences. Using fMRI in combination with a delayed-discrimination task in healthy volunteers of both sexes, we discovered that brain regions involved in this working memory encoding process were dissociable according to whether the to-be-remembered stimulus was painful or not, with the medial thalamus and the rostral anterior cingulate cortex encoding painful and the primary somatosensory cortex encoding nonpainful stimuli. Encoding of painful stimuli furthermore significantly enhanced functional connectivity between the thalamus and medial prefrontal cortex (mPFC). With regards to emotional aspects influencing encoding processes, we observed that more anxious participants showed significant performance advantages when encoding painful stimuli. Importantly, only during the encoding of pain, the interindividual differences in anxiety were associated with the strength of coupling between medial thalamus and mPFC, which was furthermore related to activity in the amygdala. These results indicate not only that there is a distinct signature for the encoding of a painful experience in humans, but also that this encoding process involves a strong affective component. SIGNIFICANCE STATEMENT To convert the sensation of pain into a briefly maintainable construct is essential to guide human behavior and avoid dangerous situations. Although this working memory encoding process is implicitly contained in the majority of studies, the underlying neural mechanisms remain unclear. Using fMRI in a delayed-discrimination task, we found that the

A deep auto-encoder model for gene expression prediction.

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Xie, Rui; Wen, Jia; Quitadamo, Andrew; Cheng, Jianlin; Shi, Xinghua

2017-11-17

Gene expression is a key intermediate level that genotypes lead to a particular trait. Gene expression is affected by various factors including genotypes of genetic variants. With an aim of delineating the genetic impact on gene expression, we build a deep auto-encoder model to assess how good genetic variants will contribute to gene expression changes. This new deep learning model is a regression-based predictive model based on the MultiLayer Perceptron and Stacked Denoising Auto-encoder (MLP-SAE). The model is trained using a stacked denoising auto-encoder for feature selection and a multilayer perceptron framework for backpropagation. We further improve the model by introducing dropout to prevent overfitting and improve performance. To demonstrate the usage of this model, we apply MLP-SAE to a real genomic datasets with genotypes and gene expression profiles measured in yeast. Our results show that the MLP-SAE model with dropout outperforms other models including Lasso, Random Forests and the MLP-SAE model without dropout. Using the MLP-SAE model with dropout, we show that gene expression quantifications predicted by the model solely based on genotypes, align well with true gene expression patterns. We provide a deep auto-encoder model for predicting gene expression from SNP genotypes. This study demonstrates that deep learning is appropriate for tackling another genomic problem, i.e., building predictive models to understand genotypes' contribution to gene expression. With the emerging availability of richer genomic data, we anticipate that deep learning models play a bigger role in modeling and interpreting genomics.

Ten years of lipoprotein apheresis for familial hypercholesterolemia in Malaysia: A creative approach by a cardiologist in a developing country.

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Khoo, Kah Lin; Page, Michael M; Liew, Yin Mei; Defesche, Joep C; Watts, Gerald F

2016-01-01

Familial hypercholesterolemia (FH) leads to premature coronary artery disease and aortic stenosis, with undertreated severe forms causing death at a young age. Lipoprotein apheresis (LA) is often required for lowering low-density lipoprotein cholesterol levels in severe FH. The objective of this study was to present the first experiences with LA in Malaysia, between 2004 and 2014. We retrospectively collected data from patient records to assess the effectiveness, adverse effects, patient quality of life, and costs associated with an LA service for genetically confirmed homozygous and heterozygous FH. We treated 13 women and 2 men aged 6 to 59 years, 10 with homozygous and 5 with heterozygous FH, all on maximally tolerated cholesterol-lowering drug therapy, for a total of 65 patient-years. Acute lowering of low-density lipoprotein cholesterol post apheresis was 56.3 ± 7.2%, with time-averaged mean lowering of 34.9 ± 13.9%. No patients experienced any cardiovascular events during the period of receiving LA. Patients receiving LA experienced few side effects and enjoyed reasonable quality of life, but inability to continue treatment was frequent because of cost. LA for severe FH can be delivered effectively in the short term in developing nations, but costs are a major barrier to sustaining this mode of treatment for this high-risk group of patients. New drug therapies for FH, such as the proprotein convertase subtilisin/kexin type 9 inhibitors, microsomal triglyceride transfer protein inhibitors, and apolipoprotein-B100 antisense oligonucleotides may allow improved care for these patients, but costs and long-term safety remain as issues to be addressed. Copyright © 2016 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Synergistic Cardioprotective Effects of Combined Chromium Picolinate and Atorvastatin Treatment in Triton X-100-Induced Hyperlipidemia in Rats: Impact on Some Biochemical Markers.

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Shafik, Noha M; Baalash, Amal; Ebeid, Abla M

2017-12-01

Hyperlipidemia is one of the major risk factors for atherosclerosis and ischemic heart disease. Chromium (Cr) mineral is playing a crucial role in glucose and lipid homeostasis. The aim of this study was to evaluate the protective effects of combined chromium picolinate (CrPic) and atorvastatin treatment against hyperlipidemia-induced cardiac injury. Seventy-five male albino rats were divided into five groups (15 rats each). Hyperlipidemia was induced by intraperitoneal injection of a single dose of Triton X-100 (300 mg/kg body weight (b.w) (group ІІ). Treatment of hyperlipidemic rats was induced by daily administration of CrPic at a dose of 200 μg/kg b.w/day (group ІІІ), atorvastatin at a dose of 10 mg/kg/day (group IV), and combined treatment with both (group V) by gavage for 7 days. At the end of experiment, serum and heart tissues were obtained. Hyperlipidemia was confirmed by histopathology of heart tissues, marked serum dyslipidemia, increased atherogenic indices, and values of ischemia-modified albumin. In addition to increased values of proprotein convertase subtilisin/kexin type 9, activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase enzyme and high relative expression levels of pentraxin-3 were observed. However, paraoxonase-1 activity was markedly decreased in the hyperlipidemic group. Significant improvement in all assessed parameters was observed in the rat group treated with both CrPic and atorvastatin. It can be concluded that combined CrPic and atorvastatin treatments had synergistic cardioprotective effects against hyperlipidemia which may be through modulating atherosclerosis as well as cardiac and aortic damage and/or activation of anti-inflammatory and anti-oxidant pathways, thus reversing endothelial dysfunction.

A dual-type responsive electrochemical immunosensor for quantitative detection of PCSK9 based on n-C60-PdPt/N-GNRs and Pt-poly (methylene blue) nanocomposites.

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Li, Yan; He, Junlin; Chen, Jun; Niu, Yazhen; Zhao, Yilin; Zhang, Yuchan; Yu, Chao

2018-03-15

In this study, a dual-type responsive electrochemical immunosensor was developed for the quantitative detection of proprotein convertase subtilisin/kexin type 9 (PCSK9), a potential biomarker of cardiovascular disease in serum. N-doped graphene nanoribbons (N-GNRs) with good conductivity were used as the sensing matrix modifying the glassy carbon electrode. Palladium platinum alloy (PdPt) nanoparticles with high catalytic performance toward the reduction of hydrogen peroxide (H 2 O 2 ) were reduced onto amino-functionalized fullerene (n-C 60 -PdPt) and significantly amplified the electrochemical signal recorded by the amperometric i-t curve. Furthermore, staphylococcus protein A (SPA) with antibody orientation function was introduced to improve the immunoreaction efficiency. Accordingly, a label-free immunosensor was fabricated based on n-C 60 -PdPt/N-GNRs for the quick detection of PCSK9. Meanwhile, to realize ultrasensitive detection of PCSK9, Pt-poly (methylene blue) (Pt-PMB) nanocomposites synthesized by a one-pot method for the first time were used as a novel signal label, which exhibited uniform morphology as well as good conductivity and produced an electrochemical signal recorded by differential pulse voltammetry (DPV). Herein, a novel sandwich-type immunosensor was designed using n-C 60 -PdPt/N-GNRs as the sensing matrix and Pt-PMB as the signal label for sensitive detection of PCSK9. Under optimal conditions, the label-free immunosensor showed a linear range of 10pgmL -1 to 100ngmL -1 with a detection limit of 3.33pgmL -1 (S/N=3), and the sandwich-type immunosensor exhibited a linear range of 100 fg mL -1 to 100ngmL -1 with a detection limit of 0.033pgmL -1 (S/N=3) for PCSK9 detection, indicating its potential application in clinical bioassay analysis. Copyright © 2017 Elsevier B.V. All rights reserved.

Homozygous Familial Hypercholesterolemia Patients With Identical Mutations Variably Express the LDLR (Low-Density Lipoprotein Receptor): Implications for the Efficacy of Evolocumab.

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Thedrez, Aurélie; Blom, Dirk J; Ramin-Mangata, Stéphane; Blanchard, Valentin; Croyal, Mikaël; Chemello, Kévin; Nativel, Brice; Pichelin, Matthieu; Cariou, Bertrand; Bourane, Steeve; Tang, Lihua; Farnier, Michel; Raal, Frederick J; Lambert, Gilles

2018-03-01

Evolocumab, a PCSK9 (proprotein convertase subtilisin kexin type 9)-neutralizing antibody, lowers low-density lipoprotein cholesterol (LDL-C) in homozygous familial hypercholesterolemic (HoFH) patients with reduced LDLR (low-density lipoprotein receptor) function. However, their individual responses are highly variable, even among carriers of identical LDLR genetic defects. We aimed to elucidate why HoFH patients variably respond to PCSK9 inhibition. Lymphocytes were isolated from 22 HoFH patients enrolled in the TAUSSIG trial (Trial Assessing Long Term Use of PCSK9 Inhibition in Subjects With Genetic LDL Disorders). Ten patients were true homozygotes (FH1/FH1) and 5 identical compound heterozygotes (FH1/FH2). Lymphocytes were plated with or without mevastatin, recombinant PCSK9 (rPCSK9), or a PCSK9-neutralizing antibody. Cell surface LDLR expression was analyzed by flow cytometry. All HoFH lymphocytes had reduced cell surface LDLR expression compared with non-FH lymphocytes, for each treatment modality. Lymphocytes from FH1/FH2 patients (LDLR defective/negative) displayed the lowest LDLR expression levels followed by lymphocytes from FH1/FH1 patients (defective/defective). Mevastatin increased, whereas rPCSK9 reduced LDLR expression. The PCSK9-neutralizing antibody restored LDLR expression. Lymphocytes displaying higher LDLR expression levels were those isolated from patients presenting with lowest levels of LDL-C and apolipoprotein B, before and after 24 weeks of evolocumab treatment. These negative correlations remained significant in FH1/FH1 patients and appeared more pronounced when patients with apolipoprotein E3/E3 genotypes were analyzed separately. Significant positive correlations were found between the levels of LDLR expression and the percentage reduction in LDL-C on evolocumab treatment. Residual LDLR expression in HoFH is a major determinant of LDL-C levels and seems to drive their individual response to evolocumab. © 2017 American Heart Association

Clinical Profile of Statin Intolerance in the Phase 3 GAUSS-2 Study.

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Cho, Leslie; Rocco, Michael; Colquhoun, David; Sullivan, David; Rosenson, Robert S; Dent, Ricardo; Xue, Allen; Scott, Rob; Wasserman, Scott M; Stroes, Erik

2016-06-01

Recent evidence suggests that statin intolerance may be more common than reported in randomized trials. However, the statin-intolerant population is not well characterized. The goal of this report is to characterize the population enrolled in the phase 3 Goal Achievement after Utilizing an anti-PCSK9 antibody in Statin Intolerant Subjects Study (GAUSS-2; NCT 01763905). GAUSS-2 compared evolocumab, a fully human monoclonal antibody to proprotein convertase subtilisin/kexin type 9 (PCSK9) to ezetimibe in hypercholesterolemic patients who discontinued statin therapy due to statin-associated muscle symptoms (SAMS). GAUSS-2 was a 12-week, double-blind, placebo-controlled, randomized study that enrolled patients with elevated LDL-C who were either not on a statin or able to tolerate only a low-dose due to SAMS. Patients had received ≥2 statins and were unable to tolerate any statin dose or increase in dose above a specified weekly dose due to SAMS. Three hundred seven patients (mean [SD] age, 62 [10] years; 54 % males) were randomized 2:1 (evolocumab:ezetimibe). Mean (SD) LDL-C was 4.99 (1.51) mmol/L. Patients had used ≥2 (100 %), ≥3 (55 %), or ≥4 (21 %) statins. Coronary artery disease was present in 29 % of patients. Statin-intolerant symptoms were myalgia in 80 % of patients, weakness in 39 %, and more serious complications in 20 %. In 98 % of patients, SAMS interfered with normal daily activity; in 52 %, symptoms precluded moderate exertion. Evaluation of the GAUSS-2 trial population of statin-intolerant patients demonstrates that most patients were high risk with severely elevated LDL-C and many had statin-associated muscle symptoms that interfered with their quality of life.

Tissue distribution and effects of fasting and obesity on the ghrelin axis in mice.

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Morash, Michael G; Gagnon, Jeffrey; Nelson, Stephanie; Anini, Younes

2010-08-09

Ghrelin is a 28 amino acid peptide hormone derived from the 117 amino acid proghrelin, following cleavage by proprotein convertase 1 (PC1). In this study, we comprehensively assessed the tissue distribution and the effect of fasting and obesity on preproghrelin, Exon-4D, PC1 and GOAT expression and proghrelin-derived peptide (PGDP) secretion. The stomach was the major source of preproghrelin expression and PDGPs, followed by the small intestine. The remaining peripheral tissues (including the brain and pancreas) contained negligible expression levels. We detected obestatin in all stomach proghrelin cells, however, 22% of proghrelin cells in the small intestine did not express obestatin. There were strain differences in ghrelin secretion in response to fasting between CD1 and C57BL/6 mice. After a 24 hour-fast, CD1 mice had increased plasma levels of total ghrelin and obestatin with no change in preproghrelin mRNA or PGDP tissues levels. C57BL/6 mice showed a different response to a 24 hour-fast having increased proghrelin mRNA expression, stomach acylated ghrelin peptide and no change in plasma obestatin in C57BL/6 mice. In obese mice (ob/ob and diet-induced obesity (DIO)) there was a significant increase in preproghrelin mRNA levels while tissue and plasma PGDP levels were significantly reduced. Fasting did not affect PGDP in obese mice. Obese models displayed differences in GOAT expression, which was elevated in DIO mice, but reduced in ob/ob mice. We did not find co-localization of the leptin receptor in ghrelin expressing stomach cells, ruling out a direct effect of leptin on stomach ghrelin synthesis and secretion. Copyright (c) 2010 Elsevier B.V. All rights reserved.

Determination of High-affinity Antibody-antigen Binding Kinetics Using Four Biosensor Platforms.

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Yang, Danlin; Singh, Ajit; Wu, Helen; Kroe-Barrett, Rachel

2017-04-17

Label-free optical biosensors are powerful tools in drug discovery for the characterization of biomolecular interactions. In this study, we describe the use of four routinely used biosensor platforms in our laboratory to evaluate the binding affinity and kinetics of ten high-affinity monoclonal antibodies (mAbs) against human proprotein convertase subtilisin kexin type 9 (PCSK9). While both Biacore T100 and ProteOn XPR36 are derived from the well-established Surface Plasmon Resonance (SPR) technology, the former has four flow cells connected by serial flow configuration, whereas the latter presents 36 reaction spots in parallel through an improvised 6 x 6 crisscross microfluidic channel configuration. The IBIS MX96 also operates based on the SPR sensor technology, with an additional imaging feature that provides detection in spatial orientation. This detection technique coupled with the Continuous Flow Microspotter (CFM) expands the throughput significantly by enabling multiplex array printing and detection of 96 reaction sports simultaneously. In contrast, the Octet RED384 is based on the BioLayer Interferometry (BLI) optical principle, with fiber-optic probes acting as the biosensor to detect interference pattern changes upon binding interactions at the tip surface. Unlike the SPR-based platforms, the BLI system does not rely on continuous flow fluidics; instead, the sensor tips collect readings while they are immersed in analyte solutions of a 384-well microplate during orbital agitation. Each of these biosensor platforms has its own advantages and disadvantages. To provide a direct comparison of these instruments' ability to provide quality kinetic data, the described protocols illustrate experiments that use the same assay format and the same high-quality reagents to characterize antibody-antigen kinetics that fit the simple 1:1 molecular interaction model.

Stairs instead of elevators at the workplace decreases PCSK9 levels in a healthy population.

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Kamani, Christel H; Gencer, Baris; Montecucco, Fabrizio; Courvoisier, Delphine; Vuilleumier, Nicolas; Meyer, Philippe; Mach, François

2015-10-01

Regular physical activity is recommended to lower low-density lipoprotein cholesterol (LDL-C) in a healthy population. Inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9) was shown to reduce (LDL-C) levels; however, the impact of physical exercise on PCSK9 levels remains unclear. We used data from 67 healthy hospital employees who participated in a 6-month intervention promoting active use of stairs instead of elevators during 3 months, followed by 3 months without recommendation. We confirmed the degree of physical activity with estimated aerobic capacity (VO2 max ) and measured serum PCSK9 levels at baseline, 3 and 6 month. Using a multilevel regression model, we analysed changes of PCSK9 levels over time adjusting for age, gender, aerobic capacity, baseline LDL-C, and LDL-C and body mass index (BMI) changes. At baseline, PCSK9 levels were associated with higher aerobic capacity (P-value = 0·024). At 3 months, we observed a significant decrease in mean PCSK9 levels from 403·6 to 324·3 ng/mL (P-value = 0·001), as well a significant decrease in mean LDL-C levels from 3·5 to 3·3 mM (P-value = 0·01). During this period, mean aerobic capacity (VO2 max ) increased from 37·0 to 40·4 mL/kg/min (P-value < 0·001). Physical activity was independently associated with a decrease in PCSK9 levels after adjustment for age, gender, baseline aerobic capacity, and LDL-C and BMI changes. Daily physical activity at the work place is independently associated with a decrease in PCSK9 levels over time. © 2015 Stichting European Society for Clinical Investigation Journal Foundation.

Matrix metalloproteinase-14 mediates a phenotypic shift in the airways to increase mucin production.

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Deshmukh, Hitesh S; McLachlan, Anne; Atkinson, Jeffrey J; Hardie, William D; Korfhagen, Thomas R; Dietsch, Maggie; Liu, Yang; Di, Peter Y P; Wesselkamper, Scott C; Borchers, Michael T; Leikauf, George D

2009-11-01

Induced mainly by cigarette smoking, chronic obstructive pulmonary disease (COPD) is a global public health problem characterized by progressive difficulty in breathing and increased mucin production. Previously, we reported that acrolein levels found in COPD sputum could activate matrix metalloproteinase-9 (MMP9). To determine whether acrolein increases expression and activity of MMP14, a critical membrane-bound endopeptidase that can initial a MMP-activation cascade. MMP14 activity and adduct formation were measured following direct acrolein treatment. MMP14 expression and activity was measured in human airway epithelial cells. MMP14 immunohistochemistry was performed with COPD tissue, and in acrolein- or tobacco-exposed mice. In a cell-free system, acrolein, in concentrations equal to those found in COPD sputum, directly adducted cysteine 319 in the MMP14 hemopexin-like domain and activated MMP14. In cells, acrolein increased MMP14 activity, which was inhibited by a proprotein convertase inhibitor, hexa-d-arginine. In the airway epithelium of COPD subjects, immunoreactive MMP14 protein increased. In mouse lung, acrolein or tobacco smoke increased lung MMP14 activity and protein. In cells, acrolein-induced MMP14 transcripts were inhibited by an epidermal growth factor receptor (EGFR) neutralizing antibody, EGFR kinase inhibitor, metalloproteinase inhibitor, or mitogen-activated protein kinase (MAPK) 3/2 or MAPK8 inhibitors, but not a MAPK14 inhibitor. Decreasing the MMP14 protein and activity in vitro by small interfering (si)RNA to MMP14 diminished the acrolein-induced MUC5AC transcripts. In acrolein-exposed mice or transgenic mice with lung-specific transforming growth factor-alpha (an EGFR ligand) expression, lung MMP14 and MUC5AC levels increased and these effects were inhibited by a EGFR inhibitor, erlotinib. Taken together, these findings implicate acrolein-induced MMP14 expression and activity in mucin production in COPD.

Effects of dietary fucoxanthin on cholesterol metabolism in diabetic/obese KK-Ay mice

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Beppu Fumiaki

2012-09-01

Full Text Available Abstract Background Fucoxanthin is a xanthophyll present in brown seaweeds and has several beneficial effects, including anti-obesity and anti-diabetic effects. However, we and another group previously observed that fucoxanthin increases serum cholesterol levels in rodents. Cholesterol is an important component of cell membranes and biosynthesis of bile acids. Serum cholesterol levels are also closely associated with atherosclerosis. Therefore, we sought to identify the mechanism underlying the increase in serum cholesterol levels by fucoxanthin. Methods Diabetic/obese KK-Ay mice were fed a diet containing 0.2% fucoxanthin for 4 weeks. The mice were sacrificed, and total blood samples were collected for the measurement of serum total cholesterol, HDL-cholesterol and non-HDL-cholesterol levels. Cholesterol content in tissues was also analyzed. Real-time PCR and Western blotting were performed to determine hepatic mRNA and protein expression of genes involved in cholesterol metabolism, respectively. Results Dietary fucoxanthin significantly increased serum HDL and non-HDL cholesterol levels, and reduced hepatic cholesterol content. In liver, the expression of SREBP1, SREBP2 and their target genes involved in cholesterol biosynthesis significantly increased and tended to increase in the fucoxanthin-fed mice, respectively. In contrast, hepatic levels of LDLR and SR-B1 proteins which is important factors for LDL-cholesterol and HDL-cholesterol uptake in the liver from serum, decreased to 60% and 80% in the fucoxanthin-fed mice, respectively, compared with the control mice. Further, we found that dietary fucoxanthin significantly increased the mRNA expression of proprotein convertase subtilisin/kexin type 9 (PCSK9, which enhances intracellular degradation of LDLR in lysosomes. Conclusions Fucoxanthin increased HDL-cholesterol and non-HDL-cholesterol levels in KK-Ay mice by inducing SREBP expression and reduced cholesterol uptake in the liver via

New developments in atherosclerosis: clinical potential of PCSK9 inhibition

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Giunzioni I

2015-08-01

Full Text Available Ilaria Giunzioni, Hagai Tavori Knight Cardiovascular Institute, Center for Preventive Cardiology, Oregon Health and Science University, Portland, OR, USA Abstract: Pro-protein convertase subtilisin/kexin type 9 (PCSK9 is a secreted 692-amino acid protein that binds surface low-density lipoprotein (LDL receptor (LDLR and targets it toward lysosomal degradation. As a consequence, the number of LDLRs at the cell surface is decreased, and LDL-cholesterol (LDL-C clearance is reduced, a phenomenon that is magnified by gain-of-function mutations of PCSK9. In contrast, loss-of-function mutations of PCSK9 result in increased surface LDLR and improved LDL-C clearance. This provides the rationale for targeting PCSK9 in hypercholesterolemic subjects as a means to lower LDL-C levels. Monoclonal antibodies (mAbs against PCSK9 that block its interaction with the LDLR have been developed in the past decade. Two companies have recently received the approval for their anti-PCSK9 mAbs by the US Food and Drug Administration (FDA and the European Medicines Agency (EMA Regeneron/Sanofi, with alirocumab (commercial name – PRALUENT® and, Amgen with evolocumab (commercial name – Repatha™. The introduction of anti-PCSK9 mAbs will provide an alternative therapeutic strategy to address many of the unmet needs of current lipid-lowering therapies, such as inability to achieve goal LDL-C level, or intolerance and aversion to statins. This review will focus on the kinetics of PCSK9, pharmacokinetics and pharmacodynamics of anti-PCSK9 mAbs, and recent data linking PCSK9 and anti-PCSK9 mAbs to cardiovascular events. Moreover, it will highlight the unanswered questions that still need to be addressed in order to understand the physiologic function, kinetics, and dynamics of PCSK9. Keywords: PCSK9, LDLR, monoclonal antibodies, pharmacokinetics, cardiovascular risk

PCSK9 inhibitors in the current management of atherosclerosis.

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Whayne, Thomas F

The history of proprotein convertase subtilisin/kexin type 9 (PCSK9) in medical science is fascinating and the evolution of knowledge of its function has resulted in new medications of major importance for the cardiovascular (CV) patient. PCSK9 functions as a negative control or feedback for the cell surface receptors for low-density lipoprotein including its component of cholesterol (LDL-C). The initial and key findings were that different abnormalities of PCSK9 can result in an increase or a decrease of LDL-C because of more or less suppression of cell surface receptors. These observations gave hints and awoke interest that it might be possible to prepare monoclonal antibodies to PCSK9 and decrease its activity, after which there should be more active LDL-C cell receptors. The rest is a fascinating story that currently has resulted in two PCSK9 inhibitors, alirocumab and evolocumab, which, on average, decrease LDL-C approximately 50%. Nevertheless, if there are no contraindications, statins remain the standard of prevention for the high-risk CV patient and this includes both secondary and primary prevention. The new inhibitors are for the patient that does not attain the desired target for LDL-C reduction while taking a maximum statin dose or who does not tolerate any statin dose whatsoever. Atherosclerosis can be considered a metabolic disease and the clinician needs to realize this and think more and more of CV prevention. These inhibitors can contribute to both the stabilization and regression of atherosclerotic plaques and thereby avoid or delay major adverse cardiac events. (United States). Copyright © 2016 Instituto Nacional de Cardiología Ignacio Chávez. Publicado por Masson Doyma México S.A. All rights reserved.

PCSK9 Inhibitors Show Value for Patients and the US Health Care System.

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Cheng, Wei-Han; Gaudette, Étienne; Goldman, Dana P

2017-12-01

Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors were approved by the US Food and Drug Administration (FDA) as cholesterol-lowering therapies for patients with familial hypercholesterolemia or atherosclerotic cardiovascular disease. To estimate the long-term health and economic value of PCSK9 inhibitors for Americans (51 years and older). We conducted simulations using the Future Elderly Model, an established dynamic microsimulation model to project the lifetime outcomes for the US population aged 51 years and older. Health effects estimates and confidence intervals from published meta-analysis studies were used to project changes in life expectancy, quality-adjusted life-years, and lifetime medical spending resulting from the use of PCSK9 inhibitors. We considered two treatment scenarios: 1) current FDA eligibility and 2) an extended eligibility scenario that includes patients with no pre-existing cardiovascular disease but at high risk. We assumed that the price of PCSK9 inhibitors was discounted by 35% in the first 12 years and by 57% thereafter, with gradual uptake of the drug in eligible populations. Use of PCSK9 inhibitors by individuals covered by current FDA approval would extend life expectancy at the age of 51 years by an estimated 1.1 years and would yield a lifetime net value of $5800 per person. If use was extended to those at high risk for cardiovascular disease, PCSK9 inhibitors would generate a lifetime net benefit of $14,100 per person. Expanded access to PCSK9 inhibitors would offer positive long-term net value for patients and the US health care system at the current discounted prices. Copyright © 2017 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Microarray-based screening of differentially expressed genes in glucocorticoid-induced avascular necrosis

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Huang, Gangyong; Wei, Yibing; Zhao, Guanglei; Xia, Jun; Wang, Siqun; Wu, Jianguo; Chen, Feiyan; Chen, Jie; Shi, Jingshen

2017-01-01

The underlying mechanisms of glucocorticoid (GC)-induced avascular necrosis of the femoral head (ANFH) have yet to be fully understood, in particular the mechanisms associated with the change of gene expression pattern. The present study aimed to identify key genes with a differential expression pattern in GC-induced ANFH. E-MEXP-2751 microarray data were downloaded from the ArrayExpress database. Differentially expressed genes (DEGs) were identified in 5 femoral head samples of steroid-induced ANFH rats compared with 5 placebo-treated rat samples. Gene Ontology (GO) and pathway enrichment analyses were performed upon these DEGs. A total 93 DEGs (46 upregulated and 47 downregulated genes) were identified in GC-induced ANFH samples. These DEGs were enriched in different GO terms and pathways, including chondrocyte differentiation and detection of chemical stimuli. The enrichment map revealed that skeletal system development was interconnected with several other GO terms by gene overlap. The literature mined network analysis revealed that 5 upregulated genes were associated with femoral necrosis, including parathyroid hormone receptor 1 (PTHR1), vitamin D (1,25-Dihydroxyvitamin D3) receptor (VDR), collagen, type II, α1, proprotein convertase subtilisin/kexin type 6 and zinc finger protein 354C (ZFP354C). In addition, ZFP354C and VDR were identified to transcription factors. Furthermore, PTHR1 was revealed to interact with VDR, and α-2-macroglobulin (A2M) interacted with fibronectin 1 (FN1) in the PPI network. PTHR1 may be involved in GC-induced ANFH via interacting with VDR. A2M may also be involved in the development of GC-induced ANFH through interacting with FN1. An improved understanding of the molecular mechanisms underlying GC-induced ANFH may provide novel targets for diagnostics and therapeutic treatment. PMID:28393228

Microarray‑based screening of differentially expressed genes in glucocorticoid‑induced avascular necrosis.

Science.gov (United States)

Huang, Gangyong; Wei, Yibing; Zhao, Guanglei; Xia, Jun; Wang, Siqun; Wu, Jianguo; Chen, Feiyan; Chen, Jie; Shi, Jingshen

2017-06-01

The underlying mechanisms of glucocorticoid (GC)‑induced avascular necrosis of the femoral head (ANFH) have yet to be fully understood, in particular the mechanisms associated with the change of gene expression pattern. The present study aimed to identify key genes with a differential expression pattern in GC‑induced ANFH. E‑MEXP‑2751 microarray data were downloaded from the ArrayExpress database. Differentially expressed genes (DEGs) were identified in 5 femoral head samples of steroid‑induced ANFH rats compared with 5 placebo‑treated rat samples. Gene Ontology (GO) and pathway enrichment analyses were performed upon these DEGs. A total 93 DEGs (46 upregulated and 47 downregulated genes) were identified in GC‑induced ANFH samples. These DEGs were enriched in different GO terms and pathways, including chondrocyte differentiation and detection of chemical stimuli. The enrichment map revealed that skeletal system development was interconnected with several other GO terms by gene overlap. The literature mined network analysis revealed that 5 upregulated genes were associated with femoral necrosis, including parathyroid hormone receptor 1 (PTHR1), vitamin D (1,25‑Dihydroxyvitamin D3) receptor (VDR), collagen, type II, α1, proprotein convertase subtilisin/kexin type 6 and zinc finger protein 354C (ZFP354C). In addition, ZFP354C and VDR were identified to transcription factors. Furthermore, PTHR1 was revealed to interact with VDR, and α‑2‑macroglobulin (A2M) interacted with fibronectin 1 (FN1) in the PPI network. PTHR1 may be involved in GC‑induced ANFH via interacting with VDR. A2M may also be involved in the development of GC‑induced ANFH through interacting with FN1. An improved understanding of the molecular mechanisms underlying GC‑induced ANFH may provide novel targets for diagnostics and therapeutic treatment.

PCSK9 Induces CD36 Degradation and Affects Long-Chain Fatty Acid Uptake and Triglyceride Metabolism in Adipocytes and in Mouse Liver.

Science.gov (United States)

Demers, Annie; Samami, Samaneh; Lauzier, Benjamin; Des Rosiers, Christine; Ngo Sock, Emilienne Tudor; Ong, Huy; Mayer, Gaetan

2015-12-01

Proprotein convertase subtilisin/kexin type 9 (PCSK9) promotes the degradation of the low-density lipoprotein receptor thereby elevating plasma low-density lipoprotein cholesterol levels and the risk of coronary heart disease. Thus, the use of PCSK9 inhibitors holds great promise to prevent heart disease. Previous work found that PCSK9 is involved in triglyceride metabolism, independently of its action on low-density lipoprotein receptor, and that other yet unidentified receptors could mediate this effect. Therefore, we assessed whether PCSK9 enhances the degradation of CD36, a major receptor involved in transport of long-chain fatty acids and triglyceride storage. Overexpressed or recombinant PCSK9 induced CD36 degradation in cell lines and primary adipocytes and reduced the uptake of the palmitate analog Bodipy FL C16 and oxidized low-density lipoprotein in 3T3-L1 adipocytes and hepatic HepG2 cells, respectively. Surface plasmon resonance, coimmunoprecipitation, confocal immunofluorescence microscopy, and protein degradation pathway inhibitors revealed that PCSK9 directly interacts with CD36 and targets the receptor to lysosomes through a mechanism involving the proteasome. Importantly, the level of CD36 protein was increased by >3-fold upon small interfering RNA knockdown of endogenous PCSK9 in hepatic cells and similarly increased in the liver and visceral adipose tissue of Pcsk9(-/-) mice. In Pcsk9(-/-) mice, increased hepatic CD36 was correlated with an amplified uptake of fatty acid and accumulation of triglycerides and lipid droplets. Our results demonstrate an important role of PCSK9 in modulating the function of CD36 and triglyceride metabolism. PCSK9-mediated CD36 degradation may serve to limit fatty acid uptake and triglyceride accumulation in tissues, such as the liver. © 2015 American Heart Association, Inc.

The symmetric MSD encoder for one-step adder of ternary optical computer

Science.gov (United States)

Kai, Song; LiPing, Yan

2016-08-01

The symmetric Modified Signed-Digit (MSD) encoding is important for achieving the one-step MSD adder of Ternary Optical Computer (TOC). The paper described the symmetric MSD encoding algorithm in detail, and developed its truth table which has nine rows and nine columns. According to the truth table, the state table was developed, and the optical-path structure and circuit-implementation scheme of the symmetric MSD encoder (SME) for one-step adder of TOC were proposed. Finally, a series of experiments were designed and performed. The observed results of the experiments showed that the scheme to implement SME was correct, feasible and efficient.

Polynucleotides encoding polypeptides having beta-glucosidase activity

Science.gov (United States)

Harris, Paul; Golightly, Elizabeth

2010-03-02

The present invention relates to isolated polypeptides having beta-glucosidase activity and isolated polynucleotides encoding the polypeptides. The invention also relates to nucleic acid constructs, vectors, and host cells comprising the polynucleotides as well as methods for producing and using the polypeptides.

Toward Chemical Implementation of Encoded Combinatorial Libraries

DEFF Research Database (Denmark)

Nielsen, John; Janda, Kim D.

1994-01-01

The recent application of "combinatorial libraries" to supplement existing drug screening processes might simplify and accelerate the search for new lead compounds or drugs. Recently, a scheme for encoded combinatorial chemistry was put forward to surmount a number of the limitations possessed...

Emotional Encoding Context Leads to Memory Bias in Individuals with High Anxiety

Directory of Open Access Journals (Sweden)

Christopher Lee

2017-12-01

Full Text Available We investigated whether anxious individuals, who adopt an inherently negative mindset, demonstrate a particularly salient memory bias for words tainted by negative contexts. To this end, sequentially presented target words, overlayed onto negative or neutral pictures, were studied in separate blocks (within-subjects using a deep or shallow encoding instruction (between-subjects. Following study, in Test 1, participants completed separate recognition test blocks for the words overlayed onto the negative and the neutral contexts. Following this, in Test 2, participants completed a recognition test for the foils from each Test 1 block. We found a significant three-way interaction on Test 2, such that individuals with high anxiety who initially studied target words using a shallow encoding instruction, demonstrated significantly elevated memory for foils that were contained within the negative Test 1 block. Results show that during retrieval (Test 1, participants re-entered the mode of processing (negative or neutral engaged at encoding, tainting the encoding of foils with that same mode of processing. The findings suggest that individuals with high relative to low anxiety, adopt a particularly salient negative retrieval mode, and this creates a downstream bias in encoding and subsequent retrieval of otherwise neutral information.

Human visual system automatically encodes sequential regularities of discrete events.

Science.gov (United States)

Kimura, Motohiro; Schröger, Erich; Czigler, István; Ohira, Hideki

2010-06-01

For our adaptive behavior in a dynamically changing environment, an essential task of the brain is to automatically encode sequential regularities inherent in the environment into a memory representation. Recent studies in neuroscience have suggested that sequential regularities embedded in discrete sensory events are automatically encoded into a memory representation at the level of the sensory system. This notion is largely supported by evidence from investigations using auditory mismatch negativity (auditory MMN), an event-related brain potential (ERP) correlate of an automatic memory-mismatch process in the auditory sensory system. However, it is still largely unclear whether or not this notion can be generalized to other sensory modalities. The purpose of the present study was to investigate the contribution of the visual sensory system to the automatic encoding of sequential regularities using visual mismatch negativity (visual MMN), an ERP correlate of an automatic memory-mismatch process in the visual sensory system. To this end, we conducted a sequential analysis of visual MMN in an oddball sequence consisting of infrequent deviant and frequent standard stimuli, and tested whether the underlying memory representation of visual MMN generation contains only a sensory memory trace of standard stimuli (trace-mismatch hypothesis) or whether it also contains sequential regularities extracted from the repetitive standard sequence (regularity-violation hypothesis). The results showed that visual MMN was elicited by first deviant (deviant stimuli following at least one standard stimulus), second deviant (deviant stimuli immediately following first deviant), and first standard (standard stimuli immediately following first deviant), but not by second standard (standard stimuli immediately following first standard). These results are consistent with the regularity-violation hypothesis, suggesting that the visual sensory system automatically encodes sequential

Encoding-related brain activity during deep processing of verbal materials: a PET study.

Science.gov (United States)

Fujii, Toshikatsu; Okuda, Jiro; Tsukiura, Takashi; Ohtake, Hiroya; Suzuki, Maki; Kawashima, Ryuta; Itoh, Masatoshi; Fukuda, Hiroshi; Yamadori, Atsushi

2002-12-01

The recent advent of neuroimaging techniques provides an opportunity to examine brain regions related to a specific memory process such as episodic memory encoding. There is, however, a possibility that areas active during an assumed episodic memory encoding task, compared with a control task, involve not only areas directly relevant to episodic memory encoding processes but also areas associated with other cognitive processes for on-line information. We used positron emission tomography (PET) to differentiate these two kinds of regions. Normal volunteers were engaged in deep (semantic) or shallow (phonological) processing of new or repeated words during PET. Results showed that deep processing, compared with shallow processing, resulted in significantly better recognition performance and that this effect was associated with activation of various brain areas. Further analyses revealed that there were regions directly relevant to episodic memory encoding in the anterior part of the parahippocampal gyrus, inferior frontal gyrus, supramarginal gyrus, anterior cingulate gyrus, and medial frontal lobe in the left hemisphere. Our results demonstrated that several regions, including the medial temporal lobe, play a role in episodic memory encoding.

Automatic semantic encoding in verbal short-term memory: evidence from the concreteness effect.

Science.gov (United States)

Campoy, Guillermo; Castellà, Judit; Provencio, Violeta; Hitch, Graham J; Baddeley, Alan D

2015-01-01

The concreteness effect in verbal short-term memory (STM) tasks is assumed to be a consequence of semantic encoding in STM, with immediate recall of concrete words benefiting from richer semantic representations. We used the concreteness effect to test the hypothesis that semantic encoding in standard verbal STM tasks is a consequence of controlled, attention-demanding mechanisms of strategic semantic retrieval and encoding. Experiment 1 analysed the effect of presentation rate, with slow presentations being assumed to benefit strategic, time-dependent semantic encoding. Experiments 2 and 3 provided a more direct test of the strategic hypothesis by introducing three different concurrent attention-demanding tasks. Although Experiment 1 showed a larger concreteness effect with slow presentations, the following two experiments yielded strong evidence against the strategic hypothesis. Limiting available attention resources by concurrent tasks reduced global memory performance, but the concreteness effect was equivalent to that found in control conditions. We conclude that semantic effects in STM result from automatic semantic encoding and provide tentative explanations for the interaction between the concreteness effect and the presentation rate.

Where to start? Bottom-up attention improves working memory by determining encoding order.

Science.gov (United States)

Ravizza, Susan M; Uitvlugt, Mitchell G; Hazeltine, Eliot

2016-12-01

The present study aimed to characterize the mechanism by which working memory is enhanced for items that capture attention because of their novelty or saliency-that is, via bottom-up attention. The first experiment replicated previous research by corroborating that bottom-up attention directed to an item is sufficient for enhancing working memory and, moreover, generalized the effect to the domain of verbal working memory. The subsequent 3 experiments sought to determine how bottom-up attention affects working memory. We considered 2 hypotheses: (1) Bottom-up attention enhances the encoded representation of the stimulus, similar to how voluntary attention functions, or (2) It affects the order of encoding by shifting priority onto the attended stimulus. By manipulating how stimuli were presented (simultaneous/sequential display) and whether the cue predicted the tested items, we found evidence that bottom-up attention improves working memory performance via the order of encoding hypothesis. This finding was observed across change detection and free recall paradigms. In contrast, voluntary attention improved working memory regardless of encoding order and showed greater effects on working memory. We conclude that when multiple information sources compete, bottom-up attention prioritizes the location at which encoding should begin. When encoding order is set, bottom-up attention has little or no benefit to working memory. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Visual short-term memory: activity supporting encoding and maintenance in retinotopic visual cortex.

Science.gov (United States)

Sneve, Markus H; Alnæs, Dag; Endestad, Tor; Greenlee, Mark W; Magnussen, Svein

2012-10-15

Recent studies have demonstrated that retinotopic cortex maintains information about visual stimuli during retention intervals. However, the process by which transient stimulus-evoked sensory responses are transformed into enduring memory representations is unknown. Here, using fMRI and short-term visual memory tasks optimized for univariate and multivariate analysis approaches, we report differential involvement of human retinotopic areas during memory encoding of the low-level visual feature orientation. All visual areas show weaker responses when memory encoding processes are interrupted, possibly due to effects in orientation-sensitive primary visual cortex (V1) propagating across extrastriate areas. Furthermore, intermediate areas in both dorsal (V3a/b) and ventral (LO1/2) streams are significantly more active during memory encoding compared with non-memory (active and passive) processing of the same stimulus material. These effects in intermediate visual cortex are also observed during memory encoding of a different stimulus feature (spatial frequency), suggesting that these areas are involved in encoding processes on a higher level of representation. Using pattern-classification techniques to probe the representational content in visual cortex during delay periods, we further demonstrate that simply initiating memory encoding is not sufficient to produce long-lasting memory traces. Rather, active maintenance appears to underlie the observed memory-specific patterns of information in retinotopic cortex. Copyright © 2012 Elsevier Inc. All rights reserved.

Examining the causes of memory strength variability: recollection, attention failure, or encoding variability?

Science.gov (United States)

Koen, Joshua D; Aly, Mariam; Wang, Wei-Chun; Yonelinas, Andrew P

2013-11-01

A prominent finding in recognition memory is that studied items are associated with more variability in memory strength than new items. Here, we test 3 competing theories for why this occurs-the encoding variability, attention failure, and recollection accounts. Distinguishing among these theories is critical because each provides a fundamentally different account of the processes underlying recognition memory. The encoding variability and attention failure accounts propose that old item variance will be unaffected by retrieval manipulations because the processes producing this effect are ascribed to encoding. The recollection account predicts that both encoding and retrieval manipulations that preferentially affect recollection will affect memory variability. These contrasting predictions were tested by examining the effect of response speeding (Experiment 1), dividing attention at retrieval (Experiment 2), context reinstatement (Experiment 3), and increased test delay (Experiment 4) on recognition performance. The results of all 4 experiments confirm the predictions of the recollection account and are inconsistent with the encoding variability account. The evidence supporting the attention failure account is mixed, with 2 of the 4 experiments confirming the account and 2 disconfirming the account. These results indicate that encoding variability and attention failure are insufficient accounts of memory variance and provide support for the recollection account. Several alternative theoretical accounts of the results are also considered. PsycINFO Database Record (c) 2013 APA, all rights reserved.

A Ti plasmid-encoded enzyme required for degradation of mannopine is functionally homologous to the T-region-encoded enzyme required for synthesis of this opine in crown gall tumors.

OpenAIRE

Kim, K S; Chilton, W S; Farrand, S K

1996-01-01

The mocC gene encoded by the octopine/mannityl opine-type Ti plasmid pTi15955 is related at the nucleotide sequence level to mas1' encoded by the T region of this plasmid. While Mas1 is required for the synthesis of mannopine (MOP) by crown gall tumor cells, MocC is essential for the utilization of MOP by Agrobacterium spp. A cosmid clone of pTi15955, pYDH208, encodes mocC and confers the utilization of MOP on strain NT1 and on strain UIA5, a derivative of NT1 lacking the 450-kb cryptic plasm...

Study and realisation of a double integration charge encoder at VXI standard

International Nuclear Information System (INIS)

Leconte, A.

1994-07-01

The 16 channels charge encoder herein described equips the Phoswich scintillators which, associated with photomultiplier tubes, constitutes the first ring of the INDRA Multidetector. This 4 π Multidetector, located at GANIL at Caen, is first presented. In this encoder, two integrations are made, offering a distinction between the fast component of the signal from the detector and the slow one (decreasing times: 2,4 ns and 320ns respectively). This measurement is performed by the integration of each component within an adjustable time-gate. Apart from the two integrations, the encoder realizes the detection of the impulsion with a constant fraction discriminator, the generation of the two gates and a test function. The use of surface mounted components together with the choice of the VXI interconnection standard, also presented in this report, allowed highly integrated electronics. The encoder uses the sliding scale principle. It also includes the electronics for some programmable adjustments, the remote visualisation of important signals and the logic for the conversion. (author). 22 refs

RNAi suppressors encoded by pathogenic human viruses

NARCIS (Netherlands)

de Vries, Walter; Berkhout, Ben

2008-01-01

RNA silencing or RNAi interference (RNAi) serves as an innate antiviral mechanism in plants, fungi and animals. Human viruses, like plant viruses, encode suppressor proteins or RNAs that block or modulate the RNAi pathway. This review summarizes the mechanisms by which pathogenic human viruses

The prevalence of encoded digital trace evidence in the nonfile space of computer media(,) (.).

Science.gov (United States)

Garfinkel, Simson L

2014-09-01

Forensically significant digital trace evidence that is frequently present in sectors of digital media not associated with allocated or deleted files. Modern digital forensic tools generally do not decompress such data unless a specific file with a recognized file type is first identified, potentially resulting in missed evidence. Email addresses are encoded differently for different file formats. As a result, trace evidence can be categorized as Plain in File (PF), Encoded in File (EF), Plain Not in File (PNF), or Encoded Not in File (ENF). The tool bulk_extractor finds all of these formats, but other forensic tools do not. A study of 961 storage devices purchased on the secondary market and shows that 474 contained encoded email addresses that were not in files (ENF). Different encoding formats are the result of different application programs that processed different kinds of digital trace evidence. Specific encoding formats explored include BASE64, GZIP, PDF, HIBER, and ZIP. Published 2014. This article is a U.S. Government work and is in the public domain in the USA. Journal of Forensic Sciences published by Wiley Periodicals, Inc. on behalf of American Academy of Forensic Sciences.

Circuit variability interacts with excitatory-inhibitory diversity of interneurons to regulate network encoding capacity.

Science.gov (United States)

Tsai, Kuo-Ting; Hu, Chin-Kun; Li, Kuan-Wei; Hwang, Wen-Liang; Chou, Ya-Hui

2018-05-23

Local interneurons (LNs) in the Drosophila olfactory system exhibit neuronal diversity and variability, yet it is still unknown how these features impact information encoding capacity and reliability in a complex LN network. We employed two strategies to construct a diverse excitatory-inhibitory neural network beginning with a ring network structure and then introduced distinct types of inhibitory interneurons and circuit variability to the simulated network. The continuity of activity within the node ensemble (oscillation pattern) was used as a readout to describe the temporal dynamics of network activity. We found that inhibitory interneurons enhance the encoding capacity by protecting the network from extremely short activation periods when the network wiring complexity is very high. In addition, distinct types of interneurons have differential effects on encoding capacity and reliability. Circuit variability may enhance the encoding reliability, with or without compromising encoding capacity. Therefore, we have described how circuit variability of interneurons may interact with excitatory-inhibitory diversity to enhance the encoding capacity and distinguishability of neural networks. In this work, we evaluate the effects of different types and degrees of connection diversity on a ring model, which may simulate interneuron networks in the Drosophila olfactory system or other biological systems.

Individual differences in rate of encoding predict estimates of visual short-term memory capacity (K).

Science.gov (United States)

Jannati, Ali; McDonald, John J; Di Lollo, Vincent

2015-06-01

The capacity of visual short-term memory (VSTM) is commonly estimated by K scores obtained with a change-detection task. Contrary to common belief, K may be influenced not only by capacity but also by the rate at which stimuli are encoded into VSTM. Experiment 1 showed that, contrary to earlier conclusions, estimates of VSTM capacity obtained with a change-detection task are constrained by temporal limitations. In Experiment 2, we used change-detection and backward-masking tasks to obtain separate within-subject estimates of K and of rate of encoding, respectively. A median split based on rate of encoding revealed significantly higher K estimates for fast encoders. Moreover, a significant correlation was found between K and the estimated rate of encoding. The present findings raise the prospect that the reported relationships between K and such cognitive concepts as fluid intelligence may be mediated not only by VSTM capacity but also by rate of encoding. (c) 2015 APA, all rights reserved).

Neural encoding of the speech envelope by children with developmental dyslexia.

Science.gov (United States)

Power, Alan J; Colling, Lincoln J; Mead, Natasha; Barnes, Lisa; Goswami, Usha

2016-09-01

Developmental dyslexia is consistently associated with difficulties in processing phonology (linguistic sound structure) across languages. One view is that dyslexia is characterised by a cognitive impairment in the "phonological representation" of word forms, which arises long before the child presents with a reading problem. Here we investigate a possible neural basis for developmental phonological impairments. We assess the neural quality of speech encoding in children with dyslexia by measuring the accuracy of low-frequency speech envelope encoding using EEG. We tested children with dyslexia and chronological age-matched (CA) and reading-level matched (RL) younger children. Participants listened to semantically-unpredictable sentences in a word report task. The sentences were noise-vocoded to increase reliance on envelope cues. Envelope reconstruction for envelopes between 0 and 10Hz showed that the children with dyslexia had significantly poorer speech encoding in the 0-2Hz band compared to both CA and RL controls. These data suggest that impaired neural encoding of low frequency speech envelopes, related to speech prosody, may underpin the phonological deficit that causes dyslexia across languages. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Recalled Aspects of Original Encoding Strategies Influence Episodic Feeling of Knowing

Science.gov (United States)

Hertzog, Christopher; Fulton, Erika K.; Sinclair, Starlette M.; Dunlosky, John

2013-01-01

We tested the hypothesis that feeling of knowing (FOK) after a failed recall attempt is influenced by recalling aspects of the original encoding strategy. Individuals were instructed to use interactive imagery to encode unrelated word pairs. We manipulated item concreteness (abstract versus concrete) and item repetition at study (1 versus 3). Participants orally described the mediator produced immediately after studying each item, if any. After a delay they were given cued recall, made FOK ratings, and attempted to recall their original mediator. Concreteness and item repetition enhanced strategy recall, which had a large effect on FOKs. Controlling on strategy recall reduced the predictive validity of FOKs for recognition memory, indicating that access to original aspects of encoding influenced FOK accuracy. Confidence judgments (CJs) for correctly recognized items covaried with FOKs, but FOKs did not fully track strategy recall associations with CJs, suggesting emergent effects of strategy cues elicited by recognition tests not accessed at the time of the FOK judgment. In summary, cue-generated access to aspects of the original encoding strategy strongly influenced episodic FOK, although other influences are also implicated. PMID:23835601

An encoding technique for multiobjective evolutionary algorithms applied to power distribution system reconfiguration.

Science.gov (United States)

Guardado, J L; Rivas-Davalos, F; Torres, J; Maximov, S; Melgoza, E

2014-01-01

Network reconfiguration is an alternative to reduce power losses and optimize the operation of power distribution systems. In this paper, an encoding scheme for evolutionary algorithms is proposed in order to search efficiently for the Pareto-optimal solutions during the reconfiguration of power distribution systems considering multiobjective optimization. The encoding scheme is based on the edge window decoder (EWD) technique, which was embedded in the Strength Pareto Evolutionary Algorithm 2 (SPEA2) and the Nondominated Sorting Genetic Algorithm II (NSGA-II). The effectiveness of the encoding scheme was proved by solving a test problem for which the true Pareto-optimal solutions are known in advance. In order to prove the practicability of the encoding scheme, a real distribution system was used to find the near Pareto-optimal solutions for different objective functions to optimize.

Functional dissociation between regularity encoding and deviance detection along the auditory hierarchy.

Science.gov (United States)

Aghamolaei, Maryam; Zarnowiec, Katarzyna; Grimm, Sabine; Escera, Carles

2016-02-01

Auditory deviance detection based on regularity encoding appears as one of the basic functional properties of the auditory system. It has traditionally been assessed with the mismatch negativity (MMN) long-latency component of the auditory evoked potential (AEP). Recent studies have found earlier correlates of deviance detection based on regularity encoding. They occur in humans in the first 50 ms after sound onset, at the level of the middle-latency response of the AEP, and parallel findings of stimulus-specific adaptation observed in animal studies. However, the functional relationship between these different levels of regularity encoding and deviance detection along the auditory hierarchy has not yet been clarified. Here we addressed this issue by examining deviant-related responses at different levels of the auditory hierarchy to stimulus changes varying in their degree of deviation regarding the spatial location of a repeated standard stimulus. Auditory stimuli were presented randomly from five loudspeakers at azimuthal angles of 0°, 12°, 24°, 36° and 48° during oddball and reversed-oddball conditions. Middle-latency responses and MMN were measured. Our results revealed that middle-latency responses were sensitive to deviance but not the degree of deviation, whereas the MMN amplitude increased as a function of deviance magnitude. These findings indicated that acoustic regularity can be encoded at the level of the middle-latency response but that it takes a higher step in the auditory hierarchy for deviance magnitude to be encoded, thus providing a functional dissociation between regularity encoding and deviance detection along the auditory hierarchy. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Rotational error in path integration: encoding and execution errors in angle reproduction.

Science.gov (United States)

Chrastil, Elizabeth R; Warren, William H

2017-06-01

Path integration is fundamental to human navigation. When a navigator leaves home on a complex outbound path, they are able to keep track of their approximate position and orientation and return to their starting location on a direct homebound path. However, there are several sources of error during path integration. Previous research has focused almost exclusively on encoding error-the error in registering the outbound path in memory. Here, we also consider execution error-the error in the response, such as turning and walking a homebound trajectory. In two experiments conducted in ambulatory virtual environments, we examined the contribution of execution error to the rotational component of path integration using angle reproduction tasks. In the reproduction tasks, participants rotated once and then rotated again to face the original direction, either reproducing the initial turn or turning through the supplementary angle. One outstanding difficulty in disentangling encoding and execution error during a typical angle reproduction task is that as the encoding angle increases, so does the required response angle. In Experiment 1, we dissociated these two variables by asking participants to report each encoding angle using two different responses: by turning to walk on a path parallel to the initial facing direction in the same (reproduction) or opposite (supplementary angle) direction. In Experiment 2, participants reported the encoding angle by turning both rightward and leftward onto a path parallel to the initial facing direction, over a larger range of angles. The results suggest that execution error, not encoding error, is the predominant source of error in angular path integration. These findings also imply that the path integrator uses an intrinsic (action-scaled) rather than an extrinsic (objective) metric.

An angle encoder for super-high resolution and super-high accuracy using SelfA

Science.gov (United States)

Watanabe, Tsukasa; Kon, Masahito; Nabeshima, Nobuo; Taniguchi, Kayoko

2014-06-01

Angular measurement technology at high resolution for applications such as in hard disk drive manufacturing machines, precision measurement equipment and aspherical process machines requires a rotary encoder with high accuracy, high resolution and high response speed. However, a rotary encoder has angular deviation factors during operation due to scale error or installation error. It has been assumed to be impossible to achieve accuracy below 0.1″ in angular measurement or control after the installation onto the rotating axis. Self-calibration (Lu and Trumper 2007 CIRP Ann. 56 499; Kim et al 2011 Proc. MacroScale; Probst 2008 Meas. Sci. Technol. 19 015101; Probst et al Meas. Sci. Technol. 9 1059; Tadashi and Makoto 1993 J. Robot. Mechatronics 5 448; Ralf et al 2006 Meas. Sci. Technol. 17 2811) and cross-calibration (Probst et al 1998 Meas. Sci. Technol. 9 1059; Just et al 2009 Precis. Eng. 33 530; Burnashev 2013 Quantum Electron. 43 130) technologies for a rotary encoder have been actively discussed on the basis of the principle of circular closure. This discussion prompted the development of rotary tables which achieve reliable and high accuracy angular verification. We apply these technologies for the development of a rotary encoder not only to meet the requirement of super-high accuracy but also to meet that of super-high resolution. This paper presents the development of an encoder with 221 = 2097 152 resolutions per rotation (360°), that is, corresponding to a 0.62″ signal period, achieved by the combination of a laser rotary encoder supplied by Magnescale Co., Ltd and a self-calibratable encoder (SelfA) supplied by The National Institute of Advanced Industrial Science & Technology (AIST). In addition, this paper introduces the development of a rotary encoder to guarantee ±0.03″ accuracy at any point of the interpolated signal, with respect to the encoder at the minimum resolution of 233, that is, corresponding to a 0.0015″ signal period after

The low-frequency encoding disadvantage: Word frequency affects processing demands.

Science.gov (United States)

Diana, Rachel A; Reder, Lynne M

2006-07-01

Low-frequency words produce more hits and fewer false alarms than high-frequency words in a recognition task. The low-frequency hit rate advantage has sometimes been attributed to processes that operate during the recognition test (e.g., L. M. Reder et al., 2000). When tasks other than recognition, such as recall, cued recall, or associative recognition, are used, the effects seem to contradict a low-frequency advantage in memory. Four experiments are presented to support the claim that in addition to the advantage of low-frequency words at retrieval, there is a low-frequency disadvantage during encoding. That is, low-frequency words require more processing resources to be encoded episodically than high-frequency words. Under encoding conditions in which processing resources are limited, low-frequency words show a larger decrement in recognition than high-frequency words. Also, studying items (pictures and words of varying frequencies) along with low-frequency words reduces performance for those stimuli. Copyright 2006 APA, all rights reserved.

Cloning of human genes encoding novel G protein-coupled receptors

Energy Technology Data Exchange (ETDEWEB)

Marchese, A.; Docherty, J.M.; Heiber, M. [Univ. of Toronto, (Canada)] [and others

1994-10-01

We report the isolation and characterization of several novel human genes encoding G protein-coupled receptors. Each of the receptors contained the familiar seven transmembrane topography and most closely resembled peptide binding receptors. Gene GPR1 encoded a receptor protein that is intronless in the coding region and that shared identity (43% in the transmembrane regions) with the opioid receptors. Northern blot analysis revealed that GPR1 transcripts were expressed in the human hippocampus, and the gene was localized to chromosome 15q21.6. Gene GPR2 encoded a protein that most closely resembled an interleukin-8 receptor (51% in the transmembrane regions), and this gene, not expressed in the six brain regions examined, was localized to chromosome 17q2.1-q21.3. A third gene, GPR3, showed identity (56% in the transmembrane regions) with a previously characterized cDNA clone from rat and was localized to chromosome 1p35-p36.1. 31 refs., 5 figs., 1 tab.

What Limits the Encoding Effect of Note-Taking? A Meta-Analytic Examination

Science.gov (United States)

Kobayashi, K.

2005-01-01

Previous meta-analyses indicate that the overall encoding effect of note-taking is positive but modest. This meta-analysis of 57 note-taking versus no note-taking comparison studies explored what limits the encoding effect by examining the moderating influence of seven variables: intervention, schooling level, presentation mode and length, test…

Fluorescent-magnetic dual-encoded nanospheres: a promising tool for fast-simultaneous-addressable high-throughput analysis

Science.gov (United States)

Xie, Min; Hu, Jun; Wen, Cong-Ying; Zhang, Zhi-Ling; Xie, Hai-Yan; Pang, Dai-Wen

2012-01-01

Bead-based optical encoding or magnetic encoding techniques are promising in high-throughput multiplexed detection and separation of numerous species under complicated conditions. Therefore, a self-assembly strategy implemented in an organic solvent is put forward to fabricate fluorescent-magnetic dual-encoded nanospheres. Briefly, hydrophobic trioctylphosphine oxide-capped CdSe/ZnS quantum dots (QDs) and oleic acid-capped nano-γ-Fe2O3 magnetic particles are directly, selectively and controllably assembled on branched poly(ethylene imine)-coated nanospheres without any pretreatment, which is crucial to keep the high quantum yield of QDs and good dispersibility of γ-Fe2O3. Owing to the tunability of coating amounts of QDs and γ-Fe2O3 as well as controllable fluorescent emissions of deposited-QDs, dual-encoded nanospheres with different photoluminescent emissions and gradient magnetic susceptibility are constructed. Using this improved layer-by-layer self-assembly approach, deposition of hydrophobic nanoparticles onto hydrophilic carriers in organic media can be easily realized; meanwhile, fluorescent-magnetic dual-functional nanospheres can be further equipped with readable optical and magnetic addresses. The resultant fluorescent-magnetic dual-encoded nanospheres possess both the unique optical properties of QDs and the superparamagnetic properties of γ-Fe2O3, exhibiting good monodispersibility, huge encoding capacity and nanoscale particle size. Compared with the encoded microbeads reported by others, the nanometre scale of the dual-encoded nanospheres gives them minimum steric hindrance and higher flexibility.

Encoding model of temporal processing in human visual cortex.

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Stigliani, Anthony; Jeska, Brianna; Grill-Spector, Kalanit

2017-12-19

How is temporal information processed in human visual cortex? Visual input is relayed to V1 through segregated transient and sustained channels in the retina and lateral geniculate nucleus (LGN). However, there is intense debate as to how sustained and transient temporal channels contribute to visual processing beyond V1. The prevailing view associates transient processing predominately with motion-sensitive regions and sustained processing with ventral stream regions, while the opposing view suggests that both temporal channels contribute to neural processing beyond V1. Using fMRI, we measured cortical responses to time-varying stimuli and then implemented a two temporal channel-encoding model to evaluate the contributions of each channel. Different from the general linear model of fMRI that predicts responses directly from the stimulus, the encoding approach first models neural responses to the stimulus from which fMRI responses are derived. This encoding approach not only predicts cortical responses to time-varying stimuli from milliseconds to seconds but also, reveals differential contributions of temporal channels across visual cortex. Consistent with the prevailing view, motion-sensitive regions and adjacent lateral occipitotemporal regions are dominated by transient responses. However, ventral occipitotemporal regions are driven by both sustained and transient channels, with transient responses exceeding the sustained. These findings propose a rethinking of temporal processing in the ventral stream and suggest that transient processing may contribute to rapid extraction of the content of the visual input. Importantly, our encoding approach has vast implications, because it can be applied with fMRI to decipher neural computations in millisecond resolution in any part of the brain. Copyright © 2017 the Author(s). Published by PNAS.

Deep--deeper--deepest? Encoding strategies and the recognition of human faces.

Science.gov (United States)

Sporer, S L

1991-03-01

Various encoding strategies that supposedly promote deeper processing of human faces (e.g., character judgments) have led to better recognition than more shallow processing tasks (judging the width of the nose). However, does deeper processing actually lead to an improvement in recognition, or, conversely, does shallow processing lead to a deterioration in performance when compared with naturally employed encoding strategies? Three experiments systematically compared a total of 8 different encoding strategies manipulating depth of processing, amount of elaboration, and self-generation of judgmental categories. All strategies that required a scanning of the whole face were basically equivalent but no better than natural strategy controls. The consistently worst groups were the ones that rated faces along preselected physical dimensions. This can be explained by subjects' lesser task involvement as revealed by manipulation checks.

Storing data encoded DNA in living organisms

Science.gov (United States)

Wong,; Pak C. , Wong; Kwong K. , Foote; Harlan, P [Richland, WA

2006-06-06

Current technologies allow the generation of artificial DNA molecules and/or the ability to alter the DNA sequences of existing DNA molecules. With a careful coding scheme and arrangement, it is possible to encode important information as an artificial DNA strand and store it in a living host safely and permanently. This inventive technology can be used to identify origins and protect R&D investments. It can also be used in environmental research to track generations of organisms and observe the ecological impact of pollutants. Today, there are microorganisms that can survive under extreme conditions. As well, it is advantageous to consider multicellular organisms as hosts for stored information. These living organisms can provide as memory housing and protection for stored data or information. The present invention provides well for data storage in a living organism wherein at least one DNA sequence is encoded to represent data and incorporated into a living organism.

Three-dimensional imagery by encoding sources of X rays

International Nuclear Information System (INIS)

Magnin, Isabelle

1987-01-01

This research thesis addresses the theoretical and practical study of X ray coded sources, and thus notably aims at exploring whether it would be possible to transform a standard digital radiography apparatus (as those operated in radiology hospital departments) into a low cost three-dimensional imagery system. The author first recalls the principle of conventional tomography and improvement attempts, and describes imagery techniques based on the use of encoding openings and source encoding. She reports the modelling of an imagery system based on encoded sources of X ray, and addresses the original notion of three-dimensional response for such a system. The author then addresses the reconstruction method by considering the reconstruction of a plane object, of a multi-plane object, and of real three-dimensional object. The frequency properties and the tomographic capacities of various types of source codes are analysed. She describes a prototype tomography apparatus, and presents and discusses three-dimensional actual phantom reconstructions. She finally introduces a new principle of dynamic three-dimensional radiography which implements an acquisition technique by 'gating code'. The acquisition principle should allow the reconstruction of volumes animated by periodic deformations, such as the heart for example [fr

QR encoded smart oral dosage forms by inkjet printing.

Science.gov (United States)

Edinger, Magnus; Bar-Shalom, Daniel; Sandler, Niklas; Rantanen, Jukka; Genina, Natalja

2018-01-30

The use of inkjet printing (IJP) technology enables the flexible manufacturing of personalized medicine with the doses tailored for each patient. In this study we demonstrate, for the first time, the applicability of IJP in the production of edible dosage forms in the pattern of a quick response (QR) code. This printed pattern contains the drug itself and encoded information relevant to the patient and/or healthcare professionals. IJP of the active pharmaceutical ingredient (API)-containing ink in the pattern of QR code was performed onto a newly developed porous and flexible, but mechanically stable substrate with a good absorption capacity. The printing did not affect the mechanical properties of the substrate. The actual drug content of the printed dosage forms was in accordance with the encoded drug content. The QR encoded dosage forms had a good print definition without significant edge bleeding. They were readable by a smartphone even after storage in harsh conditions. This approach of efficient data incorporation and data storage combined with the use of smart devices can lead to safer and more patient-friendly drug products in the future. Copyright © 2017 Elsevier B.V. All rights reserved.

Source memory that encoding was self-referential: the influence of stimulus characteristics.

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Durbin, Kelly A; Mitchell, Karen J; Johnson, Marcia K

2017-10-01

Decades of research suggest that encoding information with respect to the self improves memory (self-reference effect, SRE) for items (item SRE). The current study focused on how processing information in reference to the self affects source memory for whether an item was self-referentially processed (a source SRE). Participants self-referentially or non-self-referentially encoded words (Experiment 1) or pictures (Experiment 2) that varied in valence (positive, negative, neutral). Relative to non-self-referential processing, self-referential processing enhanced item recognition for all stimulus types (an item SRE), but it only enhanced source memory for positive words (a source SRE). In fact, source memory for negative and neutral pictures was worse for items processed self-referentially than non-self-referentially. Together, the results suggest that item SRE and source SRE (e.g., remembering an item was encoded self-referentially) are not necessarily the same across stimulus types (e.g., words, pictures; positive, negative). While an item SRE may depend on the overall likelihood the item generates any association, the enhancing effects of self-referential processing on source memory for self-referential encoding may depend on how embedded a stimulus becomes in one's self-schema, and that depends, in part, on the stimulus' valence and format. Self-relevance ratings during encoding provide converging evidence for this interpretation.

Correcting false information in memory: manipulating the strength of misinformation encoding and its retraction.

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Ecker, Ullrich K H; Lewandowsky, Stephan; Swire, Briony; Chang, Darren

2011-06-01

Information that is presumed to be true at encoding but later on turns out to be false (i.e., misinformation) often continues to influence memory and reasoning. In the present study, we investigated how the strength of encoding and the strength of a later retraction of the misinformation affect this continued influence effect. Participants read an event report containing misinformation and a subsequent correction. Encoding strength of the misinformation and correction were orthogonally manipulated either via repetition (Experiment 1) or by imposing a cognitive load during reading (Experiment 2). Results suggest that stronger retractions are effective in reducing the continued influence effects associated with strong misinformation encoding, but that even strong retractions fail to eliminate continued influence effects associated with relatively weak encoding. We present a simple computational model based on random sampling that captures this effect pattern, and conclude that the continued influence effect seems to defy most attempts to eliminate it.

Testing the encoding elaboration hypothesis: The effects of exemplar ranking on recognition and recall.

Science.gov (United States)

Schnur, P

1977-11-01

Two experiments investigated the effects of exemplar ranking on retention. High-ranking exemplars are words judged to be prototypical of a given category; low-ranking exemplars are words judged to be atypical of a given category. In Experiment 1, an incidental learning paradigm was used to measure reaction time to answer an encoding question as well as subsequent recognition. It was found that low-ranking exemplars were classified more slowly but recognized better than high-ranking exemplars. Other comparisons of the effects of category encoding, rhyme encoding, and typescript encoding on response latency and recognition replicated the results of Craik and Tulving (1975). In Experiment 2, unanticipated free recall of live previously learned paired associate lists revealed that a list composed of low-ranking exemplars was better recalled than a comparable list composed of high-ranking exemplars. Moreover, this was true only when the lists were studied in the context of appropriate category cues. These findings are discussed in terms of the encoding elaboration hypothesis.

Hippocampal Contribution to Context Encoding across Development Is Disrupted following Early-Life Adversity.

Science.gov (United States)

Lambert, Hilary K; Sheridan, Margaret A; Sambrook, Kelly A; Rosen, Maya L; Askren, Mary K; McLaughlin, Katie A

2017-02-15

Context can drastically influence responses to environmental stimuli. For example, a gunshot should provoke a different response at a public park than a shooting range. Little is known about how contextual processing and neural correlates change across human development or about individual differences related to early environmental experiences. Children ( N = 60; 8-19 years, 24 exposed to interpersonal violence) completed a context encoding task during fMRI scanning using a delayed match-to-sample design with neutral, happy, and angry facial cues embedded in realistic background scenes. Outside the scanner, participants completed a memory test for context-face pairings. Context memory and neural correlates of context encoding did not vary with age. Larger hippocampal volume was associated with better context memory. Posterior hippocampus was recruited during context encoding, and greater activation in this region predicted better memory for contexts paired with angry faces. Children exposed to violence had poor memory of contexts paired with angry faces, reduced hippocampal volume, and atypical neural recruitment on encoding trials with angry faces, including reduced hippocampal activation and greater functional connectivity between hippocampus and ventrolateral prefrontal cortex (vlPFC). Greater hippocampus-vlPFC connectivity was associated with worse memory for contexts paired with angry faces. Posterior hippocampus appears to support context encoding, a process that does not exhibit age-related variation from middle childhood to late adolescence. Exposure to dangerous environments in childhood is associated with poor context encoding in the presence of threat, likely due to greater vlPFC-dependent attentional narrowing on threat cues at the expense of hippocampus-dependent processing of the broader context. SIGNIFICANCE STATEMENT The ability to use context to guide reactions to environmental stimuli promotes flexible behavior. Remarkably little research has

Post-encoding emotional arousal enhances consolidation of item memory, but not reality-monitoring source memory.

Science.gov (United States)

Wang, Bo; Sun, Bukuan

2017-03-01

The current study examined whether the effect of post-encoding emotional arousal on item memory extends to reality-monitoring source memory and, if so, whether the effect depends on emotionality of learning stimuli and testing format. In Experiment 1, participants encoded neutral words and imagined or viewed their corresponding object pictures. Then they watched a neutral, positive, or negative video. The 24-hour delayed test showed that emotional arousal had little effect on both item memory and reality-monitoring source memory. Experiment 2 was similar except that participants encoded neutral, positive, and negative words and imagined or viewed their corresponding object pictures. The results showed that positive and negative emotional arousal induced after encoding enhanced consolidation of item memory, but not reality-monitoring source memory, regardless of emotionality of learning stimuli. Experiment 3, identical to Experiment 2 except that participants were tested only on source memory for all the encoded items, still showed that post-encoding emotional arousal had little effect on consolidation of reality-monitoring source memory. Taken together, regardless of emotionality of learning stimuli and regardless of testing format of source memory (conjunction test vs. independent test), the facilitatory effect of post-encoding emotional arousal on item memory does not generalize to reality-monitoring source memory.

Total sleep deprivation does not significantly degrade semantic encoding.

Science.gov (United States)

Honn, K A; Grant, D A; Hinson, J M; Whitney, P; Van Dongen, Hpa

2018-01-17

Sleep deprivation impairs performance on cognitive tasks, but it is unclear which cognitive processes it degrades. We administered a semantic matching task with variable stimulus onset asynchrony (SOA) and both speeded and self-paced trial blocks. The task was administered at the baseline and 24 hours later after 30.8 hours of total sleep deprivation (TSD) or matching well-rested control. After sleep deprivation, the 20% slowest response times (RTs) were significantly increased. However, the semantic encoding time component of the RTs remained at baseline level. Thus, the performance impairment induced by sleep deprivation on this task occurred in cognitive processes downstream of semantic encoding.

A Run-Length Encoding Approach for Path Analysis of C. elegans Search Behavior

Directory of Open Access Journals (Sweden)

Li Huang

2016-01-01

Full Text Available The nematode Caenorhabditis elegans explores the environment using a combination of different movement patterns, which include straight movement, reversal, and turns. We propose to quantify C. elegans movement behavior using a computer vision approach based on run-length encoding of step-length data. In this approach, the path of C. elegans is encoded as a string of characters, where each character represents a path segment of a specific type of movement. With these encoded string data, we perform k-means cluster analysis to distinguish movement behaviors resulting from different genotypes and food availability. We found that shallow and sharp turns are the most critical factors in distinguishing the differences among the movement behaviors. To validate our approach, we examined the movement behavior of tph-1 mutants that lack an enzyme responsible for serotonin biosynthesis. A k-means cluster analysis with the path string-encoded data showed that tph-1 movement behavior on food is similar to that of wild-type animals off food. We suggest that this run-length encoding approach is applicable to trajectory data in animal or human mobility data.

An Encoding Technique for Multiobjective Evolutionary Algorithms Applied to Power Distribution System Reconfiguration

Directory of Open Access Journals (Sweden)

J. L. Guardado

2014-01-01

Full Text Available Network reconfiguration is an alternative to reduce power losses and optimize the operation of power distribution systems. In this paper, an encoding scheme for evolutionary algorithms is proposed in order to search efficiently for the Pareto-optimal solutions during the reconfiguration of power distribution systems considering multiobjective optimization. The encoding scheme is based on the edge window decoder (EWD technique, which was embedded in the Strength Pareto Evolutionary Algorithm 2 (SPEA2 and the Nondominated Sorting Genetic Algorithm II (NSGA-II. The effectiveness of the encoding scheme was proved by solving a test problem for which the true Pareto-optimal solutions are known in advance. In order to prove the practicability of the encoding scheme, a real distribution system was used to find the near Pareto-optimal solutions for different objective functions to optimize.

New Methods of Stereo Encoding for FM Radio Broadcasting Based on Digital Technology

Directory of Open Access Journals (Sweden)

P. Stranak

2007-12-01

Full Text Available The article describes new methods of stereo encoding for FM radio broadcasting. Digital signal processing makes possible to construct an encoder with properties that are not attainable using conventional analog solutions. The article describes the mathematical model of the encoder, on the basis of which a specific program code for DSP was developed. The article further deals with a new method of composite clipping which does not cause impurities in the output spectrum, and at the same time preserves high separation between the left and right audio channels. The application of the new method is useful mainly where there are unwanted signal overshoots on the input of the stereo encoder, e.g., in case of signal transmission from the studio to the transmitter site through a route with psychoacoustic lossy compression of data rate.

On the relationships between generative encodings, regularity, and learning abilities when evolving plastic artificial neural networks.

Directory of Open Access Journals (Sweden)

Paul Tonelli

Full Text Available A major goal of bio-inspired artificial intelligence is to design artificial neural networks with abilities that resemble those of animal nervous systems. It is commonly believed that two keys for evolving nature-like artificial neural networks are (1 the developmental process that links genes to nervous systems, which enables the evolution of large, regular neural networks, and (2 synaptic plasticity, which allows neural networks to change during their lifetime. So far, these two topics have been mainly studied separately. The present paper shows that they are actually deeply connected. Using a simple operant conditioning task and a classic evolutionary algorithm, we compare three ways to encode plastic neural networks: a direct encoding, a developmental encoding inspired by computational neuroscience models, and a developmental encoding inspired by morphogen gradients (similar to HyperNEAT. Our results suggest that using a developmental encoding could improve the learning abilities of evolved, plastic neural networks. Complementary experiments reveal that this result is likely the consequence of the bias of developmental encodings towards regular structures: (1 in our experimental setup, encodings that tend to produce more regular networks yield networks with better general learning abilities; (2 whatever the encoding is, networks that are the more regular are statistically those that have the best learning abilities.

Encoding and decoding of digital spiral imaging based on bidirectional transformation of light's spatial eigenmodes.

Science.gov (United States)

Zhang, Wuhong; Chen, Lixiang

2016-06-15

Digital spiral imaging has been demonstrated as an effective optical tool to encode optical information and retrieve topographic information of an object. Here we develop a conceptually new and concise scheme for optical image encoding and decoding toward free-space digital spiral imaging. We experimentally demonstrate that the optical lattices with ℓ=±50 orbital angular momentum superpositions and a clover image with nearly 200 Laguerre-Gaussian (LG) modes can be well encoded and successfully decoded. It is found that an image encoded/decoded with a two-index LG spectrum (considering both azimuthal and radial indices, ℓ and p) possesses much higher fidelity than that with a one-index LG spectrum (only considering the ℓ index). Our work provides an alternative tool for the image encoding/decoding scheme toward free-space optical communications.

Processing and display of medical three dimensional arrays of numerical data using octree encoding

International Nuclear Information System (INIS)

Amans, J.L.; Darier, P.

1985-01-01

Imaging modalities such as X-ray computerized Tomography (CT), Nuclear Medicine and Nuclear Magnetic Resonance can produce three-dimensional (3-D) arrays of numerical data of medical object internal structures. The analysis of 3-D data by synthetic generation of realistic images is an important area of computer graphics and imaging. We are currently developing experimental software that allows the analysis, processing and display of 3-D arrays of numerical data that are organized in a related hierarchical data structure using OCTREE (octal-tree) encoding technique based on a recursive subdivision of the data volume. The OCTREE encoding structure is an extension of the two-dimensional tree structure: the quadtree, developed for image processing applications. Before any operations, the 3-D array of data is OCTREE encoded, thereafter all processings are concerned with the encoded object. The elementary process for the elaboration of a synthetic image includes: conditioning the volume: volume partition (numerical and spatial segmentation), choice of the view-point..., two dimensional display, either by spatial integration (radiography) or by shaded surface representation. This paper introduces these different concepts and specifies the advantages of OCTREE encoding techniques in realizing these operations. Furthermore the application of the OCTREE encoding scheme to the display of 3-D medical volumes generated from multiple CT scans is presented

Polypeptides having catalase activity and polynucleotides encoding same

Energy Technology Data Exchange (ETDEWEB)

Liu, Ye; Duan, Junxin; Zhang, Yu; Tang, Lan

2017-05-02

Provided are isolated polypeptides having catalase activity and polynucleotides encoding the polypeptides. Also provided are nucleic acid constructs, vectors and host cells comprising the polynucleotides as well as methods of producing and using the polypeptides.

Evaluating standard terminologies for encoding allergy information.

Science.gov (United States)

Goss, Foster R; Zhou, Li; Plasek, Joseph M; Broverman, Carol; Robinson, George; Middleton, Blackford; Rocha, Roberto A

2013-01-01

Allergy documentation and exchange are vital to ensuring patient safety. This study aims to analyze and compare various existing standard terminologies for representing allergy information. Five terminologies were identified, including the Systemized Nomenclature of Medical Clinical Terms (SNOMED CT), National Drug File-Reference Terminology (NDF-RT), Medication Dictionary for Regulatory Activities (MedDRA), Unique Ingredient Identifier (UNII), and RxNorm. A qualitative analysis was conducted to compare desirable characteristics of each terminology, including content coverage, concept orientation, formal definitions, multiple granularities, vocabulary structure, subset capability, and maintainability. A quantitative analysis was also performed to compare the content coverage of each terminology for (1) common food, drug, and environmental allergens and (2) descriptive concepts for common drug allergies, adverse reactions (AR), and no known allergies. Our qualitative results show that SNOMED CT fulfilled the greatest number of desirable characteristics, followed by NDF-RT, RxNorm, UNII, and MedDRA. Our quantitative results demonstrate that RxNorm had the highest concept coverage for representing drug allergens, followed by UNII, SNOMED CT, NDF-RT, and MedDRA. For food and environmental allergens, UNII demonstrated the highest concept coverage, followed by SNOMED CT. For representing descriptive allergy concepts and adverse reactions, SNOMED CT and NDF-RT showed the highest coverage. Only SNOMED CT was capable of representing unique concepts for encoding no known allergies. The proper terminology for encoding a patient's allergy is complex, as multiple elements need to be captured to form a fully structured clinical finding. Our results suggest that while gaps still exist, a combination of SNOMED CT and RxNorm can satisfy most criteria for encoding common allergies and provide sufficient content coverage.

False memory and importance: can we prioritize encoding without consequence?

Science.gov (United States)

Bui, Dung C; Friedman, Michael C; McDonough, Ian M; Castel, Alan D

2013-10-01

Given the large amount of information that we encounter, we often must prioritize what information we attempt to remember. Although critical for everyday functioning, relatively little research has focused on how people prioritize the encoding of information. Recent research has shown that people can and do selectively remember information assigned with higher, relative to lower, importance. However, the mechanisms underlying this prioritization process and the consequences of these processes are still not well understood. In the present study, we sought to better understand these prioritization processes and whether implementing these processes comes at the cost of memory accuracy, by increasing false memories. We used a modified form of the Deese/Roediger-McDermott (DRM) paradigm, in which participants studied DRM lists, with each list paired with low, medium, or high point values. In Experiment 1, encoding higher values led to more false memories than did encoding lower values, possibly because prioritizing information enhanced relational processing among high-value words. In Experiment 2, disrupting relational processing selectively reduced false memories for high-value words. Finally, in Experiment 3, facilitating relational processing selectively increased false memories for low-value words. These findings suggest that while prioritizing information can enhance true memory, this process concomitantly increases false memories. Furthermore, the mechanism underlying these prioritization processes depends on the ability to successfully engage in relational processing. Thus, how we prioritize the encoding of incoming information can come at a cost in terms of accurate memory.

Expected reward modulates encoding-related theta activity before an event.

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Gruber, Matthias J; Watrous, Andrew J; Ekstrom, Arne D; Ranganath, Charan; Otten, Leun J

2013-01-01

Oscillatory brain activity in the theta frequency range (4-8 Hz) before the onset of an event has been shown to affect the likelihood of successfully encoding the event into memory. Recent work has also indicated that frontal theta activity might be modulated by reward, but it is not clear how reward expectancy, anticipatory theta activity, and memory formation might be related. Here, we used scalp electroencephalography (EEG) to assess the relationship between these factors. EEG was recorded from healthy adults while they memorized a series of words. Each word was preceded by a cue that indicated whether a high or low monetary reward would be earned if the word was successfully remembered in a later recognition test. Frontal theta power between the presentation of the reward cue and the onset of a word was predictive of later memory for the word, but only in the high reward condition. No theta differences were observed before word onset following low reward cues. The magnitude of prestimulus encoding-related theta activity in the high reward condition was correlated with the number of high reward words that were later confidently recognized. These findings provide strong evidence for a link between reward expectancy, theta activity, and memory encoding. Theta activity before event onset seems to be especially important for the encoding of motivationally significant stimuli. One possibility is that dopaminergic activity during reward anticipation mediates frontal theta activity related to memory. Copyright © 2012 Elsevier Inc. All rights reserved.

Molecular evolution of the Paramyxoviridae and Rhabdoviridae multiple-protein-encoding P gene.

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Jordan, I K; Sutter, B A; McClure, M A

2000-01-01

Presented here is an analysis of the molecular evolutionary dynamics of the P gene among 76 representative sequences of the Paramyxoviridae and Rhabdoviridae RNA virus families. In a number of Paramyxoviridae taxa, as well as in vesicular stomatitis viruses of the Rhabdoviridae, the P gene encodes multiple proteins from a single genomic RNA sequence. These products include the phosphoprotein (P), as well as the C and V proteins. The complexity of the P gene makes it an intriguing locus to study from an evolutionary perspective. Amino acid sequence alignments of the proteins encoded at the P and N loci were used in independent phylogenetic reconstructions of the Paramyxoviridae and Rhabdoviridae families. P-gene-coding capacities were mapped onto the Paramyxoviridae phylogeny, and the most parsimonious path of multiple-coding-capacity evolution was determined. Levels of amino acid variation for Paramyxoviridae and Rhabdoviridae P-gene-encoded products were also analyzed. Proteins encoded in overlapping reading frames from the same nucleotides have different levels of amino acid variation. The nucleotide architecture that underlies the amino acid variation was determined in order to evaluate the role of selection in the evolution of the P gene overlapping reading frames. In every case, the evolution of one of the proteins encoded in the overlapping reading frames has been constrained by negative selection while the other has evolved more rapidly. The integrity of the overlapping reading frame that represents a derived state is generally maintained at the expense of the ancestral reading frame encoded by the same nucleotides. The evolution of such multicoding sequences is likely a response by RNA viruses to selective pressure to maximize genomic information content while maintaining small genome size. The ability to evolve such a complex genomic strategy is intimately related to the dynamics of the viral quasispecies, which allow enhanced exploration of the adaptive

Interactions among emotional attention, encoding, and retrieval of ambiguous information: an eye-tracking study

OpenAIRE

Everaert, Jonas; Koster, Ernst

2015-01-01

Emotional biases in attention modulate encoding of emotional material into long-term memory, but little is known about the role of such attentional biases during emotional memory retrieval. The present study investigated how emotional biases in memory are related to attentional allocation during retrieval. Forty-nine individuals encoded emotionally positive and negative meanings derived from ambiguous information and then searched their memory for encoded meanings in response to a set of retr...

W-band radio-over-fiber propagation of two optically encoded wavelength channels

Science.gov (United States)

Eghbal, Morad Khosravi; Shadaram, Mehdi

2018-01-01

We propose a W-band wavelength-division multiplexing (WDM)-over-optical code-division multiple access radio-over-fiber system. This system offers capacity expansion by increasing the working frequency to millimeter wave region and by introducing optical encoding and multiwavelength multiplexing. The system's functionality is investigated by software modeling, and the results are presented. The generated signals are data modulated at 10 Gb/s and optically encoded for two wavelength channels and transmitted with a 20-km length of fiber. The received signals are optically decoded and detected. Also, encoding has improved the bit error rate (BER) versus the received optical power margin for the WDM setting by about 4 dB. In addition, the eye-diagram shows that the difference between received optical power levels at the BER of 10-12 to 10-3 is about 1.3% between two encoded channels. This method of capacity improvement is significantly important for the next generation of mobile communication, where millimeter wave signals will be widely used to deliver data to small cells.

Neural correlates of encoding processes predicting subsequent cued recall and source memory.

Science.gov (United States)

Angel, Lucie; Isingrini, Michel; Bouazzaoui, Badiâa; Fay, Séverine

2013-03-06

In this experiment, event-related potentials were used to examine whether the neural correlates of encoding processes predicting subsequent successful recall differed from those predicting successful source memory retrieval. During encoding, participants studied lists of words and were instructed to memorize each word and the list in which it occurred. At test, they had to complete stems (the first four letters) with a studied word and then make a judgment of the initial temporal context (i.e. list). Event-related potentials recorded during encoding were segregated according to subsequent memory performance to examine subsequent memory effects (SMEs) reflecting successful cued recall (cued recall SME) and successful source retrieval (source memory SME). Data showed a cued recall SME on parietal electrode sites from 400 to 1200 ms and a late inversed cued recall SME on frontal sites in the 1200-1400 ms period. Moreover, a source memory SME was reported from 400 to 1400 ms on frontal areas. These findings indicate that patterns of encoding-related activity predicting successful recall and source memory are clearly dissociated.

Episodic encoding in normal aging: attentional resources hypothesis extended to musical material.

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Blanchet, Sophie; Belleville, Sylvie; Peretz, Isabelle

2006-01-01

The goal of the present study was to examine age-related changes in musical episodic memory for novel tunes. This was conducted by manipulating the encoding condition in a recognition paradigm. After receiving memory instructions (intentional condition), older and younger participants obtained equivalent hits. In contrast, when intentional encoding was accompanied by a dancing judgment (dancing + intentional condition), the recognition performance of the older persons was severely impaired. Impaired recognition was also found when participants only judged the excerpts without being instructed to memorize them (dancing judgment condition). Although older participants demonstrated a preserved ability to perform the dancing judgment on its own, this ability was not optimal and likely precluded the initiation of more elaborate encoding strategies. These results suggest that asking older persons to divide their attention in the study phase reduces the quality of their musical encoding. Given this extension to musical material, we discuss the notion that the age-related attentional resource decline appears to be domain-general rather than specific to verbal material.

A Novel Image Encryption Algorithm Based on DNA Encoding and Spatiotemporal Chaos

Directory of Open Access Journals (Sweden)

Chunyan Song

2015-10-01

Full Text Available DNA computing based image encryption is a new, promising field. In this paper, we propose a novel image encryption scheme based on DNA encoding and spatiotemporal chaos. In particular, after the plain image is primarily diffused with the bitwise Exclusive-OR operation, the DNA mapping rule is introduced to encode the diffused image. In order to enhance the encryption, the spatiotemporal chaotic system is used to confuse the rows and columns of the DNA encoded image. The experiments demonstrate that the proposed encryption algorithm is of high key sensitivity and large key space, and it can resist brute-force attack, entropy attack, differential attack, chosen-plaintext attack, known-plaintext attack and statistical attack.

Visual Memory : The Price of Encoding Details

NARCIS (Netherlands)

Nieuwenstein, Mark; Kromm, Maria

2017-01-01

Studies on visual long-term memory have shown that we have a tremendous capacity for remembering pictures of objects, even at a highly detailed level. What remains unclear, however, is whether encoding objects at such a detailed level comes at any cost. In the current study, we examined how the

Compensating for Language Deficits in Amnesia II: H.M.’s Spared versus Impaired Encoding Categories

Directory of Open Access Journals (Sweden)

Chris Hadley

2013-03-01

Full Text Available Although amnesic H.M. typically could not recall where or when he met someone, he could recall their topics of conversation after long interference-filled delays, suggesting impaired encoding for some categories of novel events but not others. Similarly, H.M. successfully encoded into internal representations (sentence plans some novel linguistic structures but not others in the present language production studies. For example, on the Test of Language Competence (TLC, H.M. produced uncorrected errors when encoding a wide range of novel linguistic structures, e.g., violating reliably more gender constraints than memory-normal controls when encoding referent-noun, pronoun-antecedent, and referent-pronoun anaphora, as when he erroneously and without correction used the gender-inappropriate pronoun “her” to refer to a man. In contrast, H.M. never violated corresponding referent-gender constraints for proper names, suggesting that his mechanisms for encoding proper name gender-agreement were intact. However, H.M. produced no more dysfluencies, off-topic comments, false starts, neologisms, or word and phonological sequencing errors than controls on the TLC. Present results suggest that: (a frontal mechanisms for retrieving and sequencing word, phrase, and phonological categories are intact in H.M., unlike in category-specific aphasia; (b encoding mechanisms in the hippocampal region are category-specific rather than item-specific, applying to, e.g., proper names rather than words; (c H.M.’s category-specific mechanisms for encoding referents into words, phrases, and propositions are impaired, with the exception of referent gender, person, and number for encoding proper names; and (d H.M. overuses his intact proper name encoding mechanisms to compensate for his impaired mechanisms for encoding other functionally equivalent linguistic information.

The Role of Memory Activation in Creating False Memories of Encoding Context

Science.gov (United States)

Arndt, Jason

2010-01-01

Using 3 experiments, I examined false memory for encoding context by presenting Deese-Roediger-McDermott themes (Deese, 1959; Roediger & McDermott, 1995) in usual-looking fonts and by testing related, but unstudied, lure items in a font that was shown during encoding. In 2 of the experiments, testing lure items in the font used to study their…

An angle encoder for super-high resolution and super-high accuracy using SelfA

International Nuclear Information System (INIS)

Watanabe, Tsukasa; Kon, Masahito; Nabeshima, Nobuo; Taniguchi, Kayoko

2014-01-01

Angular measurement technology at high resolution for applications such as in hard disk drive manufacturing machines, precision measurement equipment and aspherical process machines requires a rotary encoder with high accuracy, high resolution and high response speed. However, a rotary encoder has angular deviation factors during operation due to scale error or installation error. It has been assumed to be impossible to achieve accuracy below 0.1″ in angular measurement or control after the installation onto the rotating axis. Self-calibration (Lu and Trumper 2007 CIRP Ann. 56 499; Kim et al 2011 Proc. MacroScale; Probst 2008 Meas. Sci. Technol. 19 015101; Probst et al Meas. Sci. Technol. 9 1059; Tadashi and Makoto 1993 J. Robot. Mechatronics 5 448; Ralf et al 2006 Meas. Sci. Technol. 17 2811) and cross-calibration (Probst et al 1998 Meas. Sci. Technol. 9 1059; Just et al 2009 Precis. Eng. 33 530; Burnashev 2013 Quantum Electron. 43 130) technologies for a rotary encoder have been actively discussed on the basis of the principle of circular closure. This discussion prompted the development of rotary tables which achieve reliable and high accuracy angular verification. We apply these technologies for the development of a rotary encoder not only to meet the requirement of super-high accuracy but also to meet that of super-high resolution. This paper presents the development of an encoder with 2 21 = 2097 152 resolutions per rotation (360°), that is, corresponding to a 0.62″ signal period, achieved by the combination of a laser rotary encoder supplied by Magnescale Co., Ltd and a self-calibratable encoder (SelfA) supplied by The National Institute of Advanced Industrial Science and Technology (AIST). In addition, this paper introduces the development of a rotary encoder to guarantee ±0.03″ accuracy at any point of the interpolated signal, with respect to the encoder at the minimum resolution of 2 33 , that is, corresponding to a 0.0015″ signal period

Exhaustive search of linear information encoding protein-peptide recognition.

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Kelil, Abdellali; Dubreuil, Benjamin; Levy, Emmanuel D; Michnick, Stephen W

2017-04-01

High-throughput in vitro methods have been extensively applied to identify linear information that encodes peptide recognition. However, these methods are limited in number of peptides, sequence variation, and length of peptides that can be explored, and often produce solutions that are not found in the cell. Despite the large number of methods developed to attempt addressing these issues, the exhaustive search of linear information encoding protein-peptide recognition has been so far physically unfeasible. Here, we describe a strategy, called DALEL, for the exhaustive search of linear sequence information encoded in proteins that bind to a common partner. We applied DALEL to explore binding specificity of SH3 domains in the budding yeast Saccharomyces cerevisiae. Using only the polypeptide sequences of SH3 domain binding proteins, we succeeded in identifying the majority of known SH3 binding sites previously discovered either in vitro or in vivo. Moreover, we discovered a number of sites with both non-canonical sequences and distinct properties that may serve ancillary roles in peptide recognition. We compared DALEL to a variety of state-of-the-art algorithms in the blind identification of known binding sites of the human Grb2 SH3 domain. We also benchmarked DALEL on curated biological motifs derived from the ELM database to evaluate the effect of increasing/decreasing the enrichment of the motifs. Our strategy can be applied in conjunction with experimental data of proteins interacting with a common partner to identify binding sites among them. Yet, our strategy can also be applied to any group of proteins of interest to identify enriched linear motifs or to exhaustively explore the space of linear information encoded in a polypeptide sequence. Finally, we have developed a webserver located at http://michnick.bcm.umontreal.ca/dalel, offering user-friendly interface and providing different scenarios utilizing DALEL.

Encoding of contextual fear memory requires de novo proteins in the prelimbic cortex

Science.gov (United States)

Rizzo, Valerio; Touzani, Khalid; Raveendra, Bindu L.; Swarnkar, Supriya; Lora, Joan; Kadakkuzha, Beena M.; Liu, Xin-An; Zhang, Chao; Betel, Doron; Stackman, Robert W.; Puthanveettil, Sathyanarayanan V.

2016-01-01

Background Despite our understanding of the significance of the prefrontal cortex in the consolidation of long-term memories (LTM), its role in the encoding of LTM remains elusive. Here we investigated the role of new protein synthesis in the mouse medial prefrontal cortex (mPFC) in encoding contextual fear memory. Methods Because a change in the association of mRNAs to polyribosomes is an indicator of new protein synthesis, we assessed the changes in polyribosome-associated mRNAs in the mPFC following contextual fear conditioning (CFC) in the mouse. Differential gene expression in mPFC was identified by polyribosome profiling (n = 18). The role of new protein synthesis in mPFC was determined by focal inhibition of protein synthesis (n = 131) and by intra-prelimbic cortex manipulation (n = 56) of Homer 3, a candidate identified from polyribosome profiling. Results We identified several mRNAs that are differentially and temporally recruited to polyribosomes in the mPFC following CFC. Inhibition of protein synthesis in the prelimbic (PL), but not in the anterior cingulate cortex (ACC) region of the mPFC immediately after CFC disrupted encoding of contextual fear memory. Intriguingly, inhibition of new protein synthesis in the PL 6 hours after CFC did not impair encoding. Furthermore, expression of Homer 3, an mRNA enriched in polyribosomes following CFC, in the PL constrained encoding of contextual fear memory. Conclusions Our studies identify several molecular substrates of new protein synthesis in the mPFC and establish that encoding of contextual fear memories require new protein synthesis in PL subregion of mPFC. PMID:28503670

The Drosophila melanogaster DmCK2beta transcription unit encodes for functionally non-redundant protein isoforms.

Science.gov (United States)

Jauch, Eike; Wecklein, Heike; Stark, Felix; Jauch, Mandy; Raabe, Thomas

2006-06-07

Genes encoding for the two evolutionary highly conserved subunits of a heterotetrameric protein kinase CK2 holoenzyme are present in all examined eukaryotic genomes. Depending on the organism, multiple transcription units encoding for a catalytically active CK2alpha subunit and/or a regulatory CK2beta subunit may exist. The phosphotransferase activity of members of the protein kinase CK2alpha family is thought to be independent of second messengers but is modulated by interaction with CK2beta-like proteins. In the genome of Drosophila melanogaster, one gene encoding for a CK2alpha subunit and three genes encoding for CK2beta-like proteins are present. The X-linked DmCK2beta transcription unit encodes for several CK2beta protein isoforms due to alternative splicing of its primary transcript. We addressed the question whether CK2beta-like proteins are redundant in function. Our in vivo experiments show that variations of the very C-terminal tail of CK2beta isoforms encoded by the X-linked DmCK2beta transcription unit influence their functional properties. In addition, we find that CK2beta-like proteins encoded by the autosomal D. melanogaster genes CK2betates and CK2beta' cannot fully substitute for a loss of CK2beta isoforms encoded by DmCK2beta.

Lower Parietal Encoding Activation Is Associated with Sharper Information and Better Memory.

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Lee, Hongmi; Chun, Marvin M; Kuhl, Brice A

2017-04-01

Mean fMRI activation in ventral posterior parietal cortex (vPPC) during memory encoding often negatively predicts successful remembering. A popular interpretation of this phenomenon is that vPPC reflects "off-task" processing. However, recent fMRI studies considering distributed patterns of activity suggest that vPPC actively represents encoded material. Here, we assessed the relationships between pattern-based content representations in vPPC, mean activation in vPPC, and subsequent remembering. We analyzed data from two fMRI experiments where subjects studied then recalled word-face or word-scene associations. For each encoding trial, we measured 1) mean univariate activation within vPPC and 2) the strength of face/scene information as indexed by pattern analysis. Mean activation in vPPC negatively predicted subsequent remembering, but the strength of pattern-based information in the same vPPC voxels positively predicted later memory. Indeed, univariate amplitude averaged across vPPC voxels negatively correlated with pattern-based information strength. This dissociation reflected a tendency for univariate reductions to maximally occur in voxels that were not strongly tuned for the category of encoded stimuli. These results indicate that vPPC activity patterns reflect the content and quality of memory encoding and constitute a striking example of lower univariate activity corresponding to stronger pattern-based information. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Left temporal and temporoparietal brain activity depends on depth of word encoding: a magnetoencephalographic study in healthy young subjects.

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Walla, P; Hufnagl, B; Lindinger, G; Imhof, H; Deecke, L; Lang, W

2001-03-01

Using a 143-channel whole-head magnetoencephalograph (MEG) we recorded the temporal changes of brain activity from 26 healthy young subjects (14 females) related to shallow perceptual and deep semantic word encoding. During subsequent recognition tests, the subjects had to recognize the previously encoded words which were interspersed with new words. The resulting mean memory performances across all subjects clearly mirrored the different levels of encoding. The grand averaged event-related fields (ERFs) associated with perceptual and semantic word encoding differed significantly between 200 and 550 ms after stimulus onset mainly over left superior temporal and left superior parietal sensors. Semantic encoding elicited higher brain activity than perceptual encoding. Source localization procedures revealed that neural populations of the left temporal and temporoparietal brain areas showed different activity strengths across the whole group of subjects depending on depth of word encoding. We suggest that the higher brain activity associated with deep encoding as compared to shallow encoding was due to the involvement of more neural systems during the processing of visually presented words. Deep encoding required more energy than shallow encoding but for all that led to a better memory performance. Copyright 2001 Academic Press.

Characterization of Sensitivity Encoded Silicon Photomultiplier (SeSP) with 1-Dimensional and 2-Dimensional Encoding for High Resolution PET/MR

Science.gov (United States)

Omidvari, Negar; Schulz, Volkmar

2015-06-01

This paper evaluates the performance of a new type of PET detectors called sensitivity encoded silicon photomultiplier (SeSP), which allows a direct coupling of small-pitch crystal arrays to the detector with a reduction in the number of readout channels. Four SeSP devices with two separate encoding schemes of 1D and 2D were investigated in this study. Furthermore, both encoding schemes were manufactured in two different sizes of 4 ×4 mm2 and 7. 73 ×7. 9 mm2, in order to investigate the effect of size on detector parameters. All devices were coupled to LYSO crystal arrays with 1 mm pitch size and 10 mm height, with optical isolation between crystals. The characterization was done for the key parameters of crystal-identification, energy resolution, and time resolution as a function of triggering threshold and over-voltage (OV). Position information was archived using the center of gravity (CoG) algorithm and a least squares approach (LSQA) in combination with a mean light matrix around the photo-peak. The positioning results proved the capability of all four SeSP devices in precisely identifying all crystals coupled to the sensors. Energy resolution was measured at different bias voltages, varying from 12% to 18% (FWHM) and paired coincidence time resolution (pCTR) of 384 ps to 1.1 ns was obtained for different SeSP devices at about 18 °C room temperature. However, the best time resolution was achieved at the highest over-voltage, resulting in a noise ratio of 99.08%.

Encoded diffractive optics for full-spectrum computational imaging

KAUST Repository

Heide, Felix; Fu, Qiang; Peng, Yifan; Heidrich, Wolfgang

2016-01-01

Diffractive optical elements can be realized as ultra-thin plates that offer significantly reduced footprint and weight compared to refractive elements. However, such elements introduce severe chromatic aberrations and are not variable, unless used in combination with other elements in a larger, reconfigurable optical system. We introduce numerically optimized encoded phase masks in which different optical parameters such as focus or zoom can be accessed through changes in the mechanical alignment of a ultra-thin stack of two or more masks. Our encoded diffractive designs are combined with a new computational approach for self-calibrating imaging (blind deconvolution) that can restore high-quality images several orders of magnitude faster than the state of the art without pre-calibration of the optical system. This co-design of optics and computation enables tunable, full-spectrum imaging using thin diffractive optics.

Encoded diffractive optics for full-spectrum computational imaging

KAUST Repository

Heide, Felix

2016-09-16

Diffractive optical elements can be realized as ultra-thin plates that offer significantly reduced footprint and weight compared to refractive elements. However, such elements introduce severe chromatic aberrations and are not variable, unless used in combination with other elements in a larger, reconfigurable optical system. We introduce numerically optimized encoded phase masks in which different optical parameters such as focus or zoom can be accessed through changes in the mechanical alignment of a ultra-thin stack of two or more masks. Our encoded diffractive designs are combined with a new computational approach for self-calibrating imaging (blind deconvolution) that can restore high-quality images several orders of magnitude faster than the state of the art without pre-calibration of the optical system. This co-design of optics and computation enables tunable, full-spectrum imaging using thin diffractive optics.

ARA-PEPs: a repository of putative sORF-encoded peptides in Arabidopsis thaliana.

Science.gov (United States)

Hazarika, Rashmi R; De Coninck, Barbara; Yamamoto, Lidia R; Martin, Laura R; Cammue, Bruno P A; van Noort, Vera

2017-01-17

Many eukaryotic RNAs have been considered non-coding as they only contain short open reading frames (sORFs). However, there is increasing evidence for the translation of these sORFs into bioactive peptides with potent signaling, antimicrobial, developmental, antioxidant roles etc. Yet only a few peptides encoded by sORFs are annotated in the model organism Arabidopsis thaliana. To aid the functional annotation of these peptides, we have developed ARA-PEPs (available at http://www.biw.kuleuven.be/CSB/ARA-PEPs ), a repository of putative peptides encoded by sORFs in the A. thaliana genome starting from in-house Tiling arrays, RNA-seq data and other publicly available datasets. ARA-PEPs currently lists 13,748 sORF-encoded peptides with transcriptional evidence. In addition to existing data, we have identified 100 novel transcriptionally active regions (TARs) that might encode 341 novel stress-induced peptides (SIPs). To aid in identification of bioactivity, we add functional annotation and sequence conservation to predicted peptides. To our knowledge, this is the largest repository of plant peptides encoded by sORFs with transcript evidence, publicly available and this resource will help scientists to effortlessly navigate the list of experimentally studied peptides, the experimental and computational evidence supporting the activity of these peptides and gain new perspectives for peptide discovery.

A linear-encoding model explains the variability of the target morphology in regeneration

Science.gov (United States)

Lobo, Daniel; Solano, Mauricio; Bubenik, George A.; Levin, Michael

2014-01-01

A fundamental assumption of today's molecular genetics paradigm is that complex morphology emerges from the combined activity of low-level processes involving proteins and nucleic acids. An inherent characteristic of such nonlinear encodings is the difficulty of creating the genetic and epigenetic information that will produce a given self-assembling complex morphology. This ‘inverse problem’ is vital not only for understanding the evolution, development and regeneration of bodyplans, but also for synthetic biology efforts that seek to engineer biological shapes. Importantly, the regenerative mechanisms in deer antlers, planarian worms and fiddler crabs can solve an inverse problem: their target morphology can be altered specifically and stably by injuries in particular locations. Here, we discuss the class of models that use pre-specified morphological goal states and propose the existence of a linear encoding of the target morphology, making the inverse problem easy for these organisms to solve. Indeed, many model organisms such as Drosophila, hydra and Xenopus also develop according to nonlinear encodings producing linear encodings of their final morphologies. We propose the development of testable models of regeneration regulation that combine emergence with a top-down specification of shape by linear encodings of target morphology, driving transformative applications in biomedicine and synthetic bioengineering. PMID:24402915

The spectro-contextual encoding and retrieval theory of episodic memory.

Science.gov (United States)

Watrous, Andrew J; Ekstrom, Arne D

2014-01-01

The spectral fingerprint hypothesis, which posits that different frequencies of oscillations underlie different cognitive operations, provides one account for how interactions between brain regions support perceptual and attentive processes (Siegel etal., 2012). Here, we explore and extend this idea to the domain of human episodic memory encoding and retrieval. Incorporating findings from the synaptic to cognitive levels of organization, we argue that spectrally precise cross-frequency coupling and phase-synchronization promote the formation of hippocampal-neocortical cell assemblies that form the basis for episodic memory. We suggest that both cell assembly firing patterns as well as the global pattern of brain oscillatory activity within hippocampal-neocortical networks represents the contents of a particular memory. Drawing upon the ideas of context reinstatement and multiple trace theory, we argue that memory retrieval is driven by internal and/or external factors which recreate these frequency-specific oscillatory patterns which occur during episodic encoding. These ideas are synthesized into a novel model of episodic memory (the spectro-contextual encoding and retrieval theory, or "SCERT") that provides several testable predictions for future research.

Learning Spatiotemporally Encoded Pattern Transformations in Structured Spiking Neural Networks.

Science.gov (United States)

Gardner, Brian; Sporea, Ioana; Grüning, André

2015-12-01

Information encoding in the nervous system is supported through the precise spike timings of neurons; however, an understanding of the underlying processes by which such representations are formed in the first place remains an open question. Here we examine how multilayered networks of spiking neurons can learn to encode for input patterns using a fully temporal coding scheme. To this end, we introduce a new supervised learning rule, MultilayerSpiker, that can train spiking networks containing hidden layer neurons to perform transformations between spatiotemporal input and output spike patterns. The performance of the proposed learning rule is demonstrated in terms of the number of pattern mappings it can learn, the complexity of network structures it can be used on, and its classification accuracy when using multispike-based encodings. In particular, the learning rule displays robustness against input noise and can generalize well on an example data set. Our approach contributes to both a systematic understanding of how computations might take place in the nervous system and a learning rule that displays strong technical capability.

Fully phase-encoded MRI near metallic implants using ultrashort echo times and broadband excitation.

Science.gov (United States)

Wiens, Curtis N; Artz, Nathan S; Jang, Hyungseok; McMillan, Alan B; Koch, Kevin M; Reeder, Scott B

2018-04-01

To develop a fully phase-encoded MRI method for distortion-free imaging near metallic implants, in clinically feasible acquisition times. An accelerated 3D fully phase-encoded acquisition with broadband excitation and ultrashort echo times is presented, which uses a broadband radiofrequency pulse to excite the entire off-resonance induced by the metallic implant. Furthermore, fully phase-encoded imaging is used to prevent distortions caused by frequency encoding, and to obtain ultrashort echo times for rapidly decaying signal. Phantom and in vivo acquisitions were used to describe the relationship among excitation bandwidth, signal loss near metallic implants, and T 1 weighting. Shorter radiofrequency pulses captured signal closer to the implant by improving spectral coverage and allowing shorter echo times, whereas longer pulses improved T 1 weighting through larger maximum attainable flip angles. Comparisons of fully phase-encoded acquisition with broadband excitation and ultrashort echo times to T 1 -weighted multi-acquisition with variable resonance image combination selective were performed in phantoms and subjects with metallic knee and hip prostheses. These acquisitions had similar contrast and acquisition efficiency. Accelerated fully phase-encoded acquisitions with ultrashort echo times and broadband excitation can generate distortion free images near metallic implants in clinically feasible acquisition times. Magn Reson Med 79:2156-2163, 2018. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society for Magnetic Resonance in Medicine.

Music improves verbal memory encoding while decreasing prefrontal cortex activity: an fNIRS study.

Science.gov (United States)

Ferreri, Laura; Aucouturier, Jean-Julien; Muthalib, Makii; Bigand, Emmanuel; Bugaiska, Aurelia

2013-01-01

Listening to music engages the whole brain, thus stimulating cognitive performance in a range of non-purely musical activities such as language and memory tasks. This article addresses an ongoing debate on the link between music and memory for words. While evidence on healthy and clinical populations suggests that music listening can improve verbal memory in a variety of situations, it is still unclear what specific memory process is affected and how. This study was designed to explore the hypothesis that music specifically benefits the encoding part of verbal memory tasks, by providing a richer context for encoding and therefore less demand on the dorsolateral prefrontal cortex (DLPFC). Twenty-two healthy young adults were subjected to functional near-infrared spectroscopy (fNIRS) imaging of their bilateral DLPFC while encoding words in the presence of either a music or a silent background. Behavioral data confirmed the facilitating effect of music background during encoding on subsequent item recognition. fNIRS results revealed significantly greater activation of the left hemisphere during encoding (in line with the HERA model of memory lateralization) and a sustained, bilateral decrease of activity in the DLPFC in the music condition compared to silence. These findings suggest that music modulates the role played by the DLPFC during verbal encoding, and open perspectives for applications to clinical populations with prefrontal impairments, such as elderly adults or Alzheimer's patients.

Music improves verbal memory encoding while decreasing prefrontal cortex activity: an fNIRS study

Directory of Open Access Journals (Sweden)

Laura eFerreri

2013-11-01

Full Text Available Listening to music engages the whole brain, thus stimulating cognitive performance in a range of non purely musical activities such as language and memory tasks. This article addresses an ongoing debate on the link between music and memory for words. While evidence on healthy and clinical populations suggests that music listening can improve verbal memory in a variety of situations, it is still unclear what specific memory process is affected and how. This study was designed to explore the hypothesis that music specifically benefits the encoding part of verbal memory tasks, by providing a richer context for encoding and therefore less demand on the dorsolateral prefrontal cortex (DLPFC. 22 healthy young adults were subjected to functional near-infrared spectroscopy (fNIRS imaging of their bilateral DLPFC while encoding words in the presence of either a music or a silent background. Behavioral data confirmed the facilitating effect of music background during encoding on subsequent item recognition. fNIRS results revealed significantly greater activation of the left hemisphere during encoding (in line with the HERA model of memory lateralization and a sustained, bilateral decrease of activity in the DLPFC in the music condition compared to silence. These findings suggest that music modulates the role played by the DLPFC during verbal encoding, and open perspectives for applications to clinical populations with prefrontal impairments, such as elderly adults or Alzheimer's patients.

Contribution of stress and sex hormones to memory encoding.

Science.gov (United States)

Merz, Christian J

2017-08-01

Distinct stages of the menstrual cycle and the intake of oral contraceptives (OC) affect sex hormone levels, stress responses, and memory processes critically involved in the pathogenesis of mental disorders. To characterize the interaction of sex and stress hormones on memory encoding, 30 men, 30 women in the early follicular phase of the menstrual cycle (FO), 30 women in the luteal phase (LU), and 30 OC women were exposed to either a stress (socially evaluated cold-pressor test) or a control condition prior to memory encoding and immediate recall of neutral, positive, and negative words. On the next day, delayed free and cued recall was tested. Sex hormone levels verified distinct estradiol, progesterone, and testosterone levels between groups. Stress increased blood pressure, cortisol concentrations, and ratings of stress appraisal in all four groups as well as cued recall performance of negative words in men. Stress exposure in OC women led to a blunted cortisol response and rather enhanced cued recall of neutral words. Thus, pre-encoding stress facilitated emotional cued recall performance in men only, but not women with different sex hormone statuses pointing to the pivotal role of circulating sex hormones in modulation of learning and memory processes. Copyright © 2017 Elsevier Ltd. All rights reserved.

New Complexity Scalable MPEG Encoding Techniques for Mobile Applications

Directory of Open Access Journals (Sweden)

Stephan Mietens

2004-03-01

Full Text Available Complexity scalability offers the advantage of one-time design of video applications for a large product family, including mobile devices, without the need of redesigning the applications on the algorithmic level to meet the requirements of the different products. In this paper, we present complexity scalable MPEG encoding having core modules with modifications for scalability. The interdependencies of the scalable modules and the system performance are evaluated. Experimental results show scalability giving a smooth change in complexity and corresponding video quality. Scalability is basically achieved by varying the number of computed DCT coefficients and the number of evaluated motion vectors but other modules are designed such they scale with the previous parameters. In the experiments using the “Stefan” sequence, the elapsed execution time of the scalable encoder, reflecting the computational complexity, can be gradually reduced to roughly 50% of its original execution time. The video quality scales between 20 dB and 48 dB PSNR with unity quantizer setting, and between 21.5 dB and 38.5 dB PSNR for different sequences targeting 1500 kbps. The implemented encoder and the scalability techniques can be successfully applied in mobile systems based on MPEG video compression.

Spectrotemporal dynamics of the EEG during working memory encoding and maintenance predicts individual behavioral capacity.

Science.gov (United States)

Bashivan, Pouya; Bidelman, Gavin M; Yeasin, Mohammed

2014-12-01

We investigated the effect of memory load on encoding and maintenance of information in working memory. Electroencephalography (EEG) signals were recorded while participants performed a modified Sternberg visual memory task. Independent component analysis (ICA) was used to factorise the EEG signals into distinct temporal activations to perform spectrotemporal analysis and localisation of source activities. We found 'encoding' and 'maintenance' operations were correlated with negative and positive changes in α-band power, respectively. Transient activities were observed during encoding of information in the bilateral cuneus, precuneus, inferior parietal gyrus and fusiform gyrus, and a sustained activity in the inferior frontal gyrus. Strong correlations were also observed between changes in α-power and behavioral performance during both encoding and maintenance. Furthermore, it was also found that individuals with higher working memory capacity experienced stronger neural oscillatory responses during the encoding of visual objects into working memory. Our results suggest an interplay between two distinct neural pathways and different spatiotemporal operations during the encoding and maintenance of information which predict individual differences in working memory capacity observed at the behavioral level. © 2014 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Digital memory encoding in Chinese dyscalculia: An event-related potential study.

Science.gov (United States)

Wang, Enguo; Qin, Shutao; Chang, MengYan; Zhu, Xiangru

2014-10-22

This study reports the neurophysiological and behavioral correlates of digital memory encoding features in Chinese individuals with and without dyscalculia. Eighteen children with dyscalculia (ages 11.5-13.5) and 18 matched controls were tested, and their event-related potentials (ERPs) were digitally recorded simultaneously with behavioral measures. The results showed that both groups had a significant Dm effect, and this effect was greater in the control group. In the 300-400-ms, 400-500-ms, and 600-700-ms processing stages, both groups showed significant differences of digital memory encoding in the frontal, central, and parietal regions. In the 500-600-ms period, the Dm effect in the control group was significantly greater than that in the dyscalculia group only in the parietal region. These results suggest that individuals with dyscalculia exhibit impaired digital memory encoding and deficits in psychological resource allocation. Copyright © 2014 Elsevier Ltd. All rights reserved.

A novel attack method about double-random-phase-encoding-based image hiding method

Science.gov (United States)

Xu, Hongsheng; Xiao, Zhijun; Zhu, Xianchen

2018-03-01

By using optical image processing techniques, a novel text encryption and hiding method applied by double-random phase-encoding technique is proposed in the paper. The first step is that the secret message is transformed into a 2-dimension array. The higher bits of the elements in the array are used to fill with the bit stream of the secret text, while the lower bits are stored specific values. Then, the transformed array is encoded by double random phase encoding technique. Last, the encoded array is embedded on a public host image to obtain the image embedded with hidden text. The performance of the proposed technique is tested via analytical modeling and test data stream. Experimental results show that the secret text can be recovered either accurately or almost accurately, while maintaining the quality of the host image embedded with hidden data by properly selecting the method of transforming the secret text into an array and the superimposition coefficient.

Cingulo-opercular activity affects incidental memory encoding for speech in noise.

Science.gov (United States)

Vaden, Kenneth I; Teubner-Rhodes, Susan; Ahlstrom, Jayne B; Dubno, Judy R; Eckert, Mark A

2017-08-15

Correctly understood speech in difficult listening conditions is often difficult to remember. A long-standing hypothesis for this observation is that the engagement of cognitive resources to aid speech understanding can limit resources available for memory encoding. This hypothesis is consistent with evidence that speech presented in difficult conditions typically elicits greater activity throughout cingulo-opercular regions of frontal cortex that are proposed to optimize task performance through adaptive control of behavior and tonic attention. However, successful memory encoding of items for delayed recognition memory tasks is consistently associated with increased cingulo-opercular activity when perceptual difficulty is minimized. The current study used a delayed recognition memory task to test competing predictions that memory encoding for words is enhanced or limited by the engagement of cingulo-opercular activity during challenging listening conditions. An fMRI experiment was conducted with twenty healthy adult participants who performed a word identification in noise task that was immediately followed by a delayed recognition memory task. Consistent with previous findings, word identification trials in the poorer signal-to-noise ratio condition were associated with increased cingulo-opercular activity and poorer recognition memory scores on average. However, cingulo-opercular activity decreased for correctly identified words in noise that were not recognized in the delayed memory test. These results suggest that memory encoding in difficult listening conditions is poorer when elevated cingulo-opercular activity is not sustained. Although increased attention to speech when presented in difficult conditions may detract from more active forms of memory maintenance (e.g., sub-vocal rehearsal), we conclude that task performance monitoring and/or elevated tonic attention supports incidental memory encoding in challenging listening conditions. Copyright © 2017

V123 Beam Synchronous Encoder Module

International Nuclear Information System (INIS)

Kerner, T.; Conkling, C. R.; Oerter, B.

1999-01-01

The V123 Synchronous Encoder Module transmits events to distributed trigger modules and embedded decoders around the RHIC rings where they are used to provide beam instrumentation triggers [1,2,3]. The RHIC beam synchronous event link hardware is mainly comprised of three VMEbus board designs, the central input modules (V201), and encoder modules (V123), and the distributed trigger modules (V124). Two beam synchronous links, one for each ring, are distributed via fiberoptic and fanned out via twisted wire pair cables. The V123 synchronizes with the RF system clock derived from the beam bucket frequency and a revolution fiducial pulse. The RF system clock is used to create the beam synchronous event link carrier and events are synchronized with the rotation fiducial. A low jitter RF clock is later recovered from this carrier by phase lock loops in the trigger modules. Prioritized hardware and software triggers fill up to 15 beam event code transmission slots per revolution while tracking the ramping RF acceleration frequency and storage frequency. The revolution fiducial event is always the first event transmitted which is used to synchronize the firing of the abort kicker and to locate the first bucket for decoders distributed about the ring

Polypeptides having cellobiohydrolase activity and polynucleotides encoding same

Science.gov (United States)

Morant, Marc D.; Harris, Paul

2015-10-13

The present invention relates to isolated polypeptides having cellobiohydrolase activity and isolated polynucleotides encoding the polypeptides. The invention also relates to nucleic acid constructs, vectors, and host cells comprising the polynucleotides as well as methods of producing and using the polypeptides.

Polypeptides having xylanase activity and polynucleotides encoding same

Energy Technology Data Exchange (ETDEWEB)

Spodsberg, Nikolaj

2018-02-06

The present invention relates to isolated polypeptides having xylanase activity and polynucleotides encoding the polypeptides. The invention also relates to nucleic acid constructs, vectors, and host cells comprising the polynucleotides as well as methods of producing and using the polypeptides.

Beta-glucosidase variants and polynucleotides encoding same

Science.gov (United States)

Wogulis, Mark; Harris, Paul; Osborn, David

2017-06-27

The present invention relates to beta-glucosidase variants, e.g. beta-glucosidase variants of a parent Family GH3A beta-glucosidase from Aspergillus fumigatus. The present invention also relates to polynucleotides encoding the beta-glucosidase variants; nucleic acid constructs, vectors, and host cells comprising the polynucleotides; and methods of using the beta-glucosidase variants.

INVESTIGATION OF INFLUENCE OF ENCODING FUNCTION COMPLEXITY ON DISTRIBUTION OF ERROR MASKING PROBABILITY

Directory of Open Access Journals (Sweden)

A. B. Levina

2016-03-01

Full Text Available Error detection codes are mechanisms that enable robust delivery of data in unreliable communication channels and devices. Unreliable channels and devices are error-prone objects. Respectively, error detection codes allow detecting such errors. There are two classes of error detecting codes - classical codes and security-oriented codes. The classical codes have high percentage of detected errors; however, they have a high probability to miss an error in algebraic manipulation. In order, security-oriented codes are codes with a small Hamming distance and high protection to algebraic manipulation. The probability of error masking is a fundamental parameter of security-oriented codes. A detailed study of this parameter allows analyzing the behavior of the error-correcting code in the case of error injection in the encoding device. In order, the complexity of the encoding function plays an important role in the security-oriented codes. Encoding functions with less computational complexity and a low probability of masking are the best protection of encoding device against malicious acts. This paper investigates the influence of encoding function complexity on the error masking probability distribution. It will be shownthat the more complex encoding function reduces the maximum of error masking probability. It is also shown in the paper that increasing of the function complexity changes the error masking probability distribution. In particular, increasing of computational complexity decreases the difference between the maximum and average value of the error masking probability. Our resultshave shown that functions with greater complexity have smoothed maximums of error masking probability, which significantly complicates the analysis of error-correcting code by attacker. As a result, in case of complex encoding function the probability of the algebraic manipulation is reduced. The paper discusses an approach how to measure the error masking

Place field assembly distribution encodes preferred locations.

Directory of Open Access Journals (Sweden)

Omar Mamad

2017-09-01

Full Text Available The hippocampus is the main locus of episodic memory formation and the neurons there encode the spatial map of the environment. Hippocampal place cells represent location, but their role in the learning of preferential location remains unclear. The hippocampus may encode locations independently from the stimuli and events that are associated with these locations. We have discovered a unique population code for the experience-dependent value of the context. The degree of reward-driven navigation preference highly correlates with the spatial distribution of the place fields recorded in the CA1 region of the hippocampus. We show place field clustering towards rewarded locations. Optogenetic manipulation of the ventral tegmental area demonstrates that the experience-dependent place field assembly distribution is directed by tegmental dopaminergic activity. The ability of the place cells to remap parallels the acquisition of reward context. Our findings present key evidence that the hippocampal neurons are not merely mapping the static environment but also store the concurrent context reward value, enabling episodic memory for past experience to support future adaptive behavior.

QualityML: a dictionary for quality metadata encoding

Science.gov (United States)

Ninyerola, Miquel; Sevillano, Eva; Serral, Ivette; Pons, Xavier; Zabala, Alaitz; Bastin, Lucy; Masó, Joan

2014-05-01

The scenario of rapidly growing geodata catalogues requires tools focused on facilitate users the choice of products. Having quality fields populated in metadata allow the users to rank and then select the best fit-for-purpose products. In this direction, we have developed the QualityML (http://qualityml.geoviqua.org), a dictionary that contains hierarchically structured concepts to precisely define and relate quality levels: from quality classes to quality measurements. Generically, a quality element is the path that goes from the higher level (quality class) to the lowest levels (statistics or quality metrics). This path is used to encode quality of datasets in the corresponding metadata schemas. The benefits of having encoded quality, in the case of data producers, are related with improvements in their product discovery and better transmission of their characteristics. In the case of data users, particularly decision-makers, they would find quality and uncertainty measures to take the best decisions as well as perform dataset intercomparison. Also it allows other components (such as visualization, discovery, or comparison tools) to be quality-aware and interoperable. On one hand, the QualityML is a profile of the ISO geospatial metadata standards providing a set of rules for precisely documenting quality indicator parameters that is structured in 6 levels. On the other hand, QualityML includes semantics and vocabularies for the quality concepts. Whenever possible, if uses statistic expressions from the UncertML dictionary (http://www.uncertml.org) encoding. However it also extends UncertML to provide list of alternative metrics that are commonly used to quantify quality. A specific example, based on a temperature dataset, is shown below. The annual mean temperature map has been validated with independent in-situ measurements to obtain a global error of 0.5 ° C. Level 0: Quality class (e.g., Thematic accuracy) Level 1: Quality indicator (e.g., Quantitative

Structural Basis for Eculizumab-Mediated Inhibition of the Complement Terminal Pathway

DEFF Research Database (Denmark)

Schatz-Jakobsen, Janus Asbjørn; zhang, yuchun; Johnson, Krista

2016-01-01

the structural observations of the interaction are supported by the reduced ability of a subset of these mutated antibodies to inhibit MAC formation as tested in a hemolysis assay. Our results suggest that eculizumab functions by sterically preventing C5 from binding to convertases and explain the exquisite......Eculizumab is a humanized monoclonal antibody approved for treatment of patients with paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uraemic syndrome. Eculizumab binds complement component C5 and prevents its cleavage by C5 convertases, inhibiting release of both...

Neural correlates of the spacing effect in explicit verbal semantic encoding support the deficient-processing theory.

Science.gov (United States)

Callan, Daniel E; Schweighofer, Nicolas

2010-04-01

Spaced presentations of to-be-learned items during encoding leads to superior long-term retention over massed presentations. Despite over a century of research, the psychological and neural basis of this spacing effect however is still under investigation. To test the hypotheses that the spacing effect results either from reduction in encoding-related verbal maintenance rehearsal in massed relative to spaced presentations (deficient processing hypothesis) or from greater encoding-related elaborative rehearsal of relational information in spaced relative to massed presentations (encoding variability hypothesis), we designed a vocabulary learning experiment in which subjects encoded paired-associates, each composed of a known word paired with a novel word, in both spaced and massed conditions during functional magnetic resonance imaging. As expected, recall performance in delayed cued-recall tests was significantly better for spaced over massed conditions. Analysis of brain activity during encoding revealed that the left frontal operculum, known to be involved in encoding via verbal maintenance rehearsal, was associated with greater performance-related increased activity in the spaced relative to massed condition. Consistent with the deficient processing hypothesis, a significant decrease in activity with subsequent episodes of presentation was found in the frontal operculum for the massed but not the spaced condition. Our results suggest that the spacing effect is mediated by activity in the frontal operculum, presumably by encoding-related increased verbal maintenance rehearsal, which facilitates binding of phonological and word level verbal information for transfer into long-term memory. Copyright 2009 Wiley-Liss, Inc.

Authentication of gold nanoparticle encoded pharmaceutical tablets using polarimetric signatures.

Science.gov (United States)

Carnicer, Artur; Arteaga, Oriol; Suñé-Negre, Josep M; Javidi, Bahram

2016-10-01

The counterfeiting of pharmaceutical products represents concerns for both industry and the safety of the general public. Falsification produces losses to companies and poses health risks for patients. In order to detect fake pharmaceutical tablets, we propose producing film-coated tablets with gold nanoparticle encoding. These coated tablets contain unique polarimetric signatures. We present experiments to show that ellipsometric optical techniques, in combination with machine learning algorithms, can be used to distinguish genuine and fake samples. To the best of our knowledge, this is the first report using gold nanoparticles encoded with optical polarimetric classifiers to prevent the counterfeiting of pharmaceutical products.

Horse cDNA clones encoding two MHC class I genes

Energy Technology Data Exchange (ETDEWEB)

Barbis, D.P.; Maher, J.K.; Stanek, J.; Klaunberg, B.A.; Antczak, D.F.

1994-12-31

Two full-length clones encoding MHC class I genes were isolated by screening a horse cDNA library, using a probe encoding in human HLA-A2.2Y allele. The library was made in the pcDNA1 vector (Invitrogen, San Diego, CA), using mRNA from peripheral blood lymphocytes obtained from a Thoroughbred stallion (No. 0834) homozygous for a common horse MHC haplotype (ELA-A2, -B2, -D2; Antczak et al. 1984; Donaldson et al. 1988). The clones were sequenced, using SP6 and T7 universal primers and horse-specific oligonucleotides designed to extend previously determined sequences.

The Role of Executive Control of Attention and Selective Encoding for Preschoolers' Learning

Science.gov (United States)

Roderer, Thomas; Krebs, Saskia; Schmid, Corinne; Roebers, Claudia M.

2012-01-01

Selectivity in encoding, aspects of attentional control and their contribution to learning performance were explored in a sample of preschoolers. While the children are performing a learning task, their encoding of relevant and attention towards irrelevant information was recorded through an eye-tracking device. Recognition of target items was…

Learning-based encoding with soft assignment for age estimation under unconstrained imaging conditions

NARCIS (Netherlands)

Alnajar, F.; Shan, C.; Gevers, T.; Geusebroek, J.M.

2012-01-01

In this paper we propose to adopt a learning-based encoding method for age estimation under unconstrained imaging conditions. A similar approach [Cao et al., 2010] is applied to face recognition in real-life face images. However, the feature vectors are encoded in hard manner i.e. each feature

Encoding instructions and stimulus presentation in local environmental context-dependent memory studies.

Science.gov (United States)

Markopoulos, G; Rutherford, A; Cairns, C; Green, J

2010-08-01

Murnane and Phelps (1993) recommend word pair presentations in local environmental context (EC) studies to prevent associations being formed between successively presented items and their ECs and a consequent reduction in the EC effect. Two experiments were conducted to assess the veracity of this assumption. In Experiment 1, participants memorised single words or word pairs, or categorised them as natural or man made. Their free recall protocols were examined to assess any associations established between successively presented items. Fewest associations were observed when the item-specific encoding task (i.e., natural or man made categorisation of word referents) was applied to single words. These findings were examined further in Experiment 2, where the influence of encoding instructions and stimulus presentation on local EC dependent recognition memory was examined. Consistent with recognition dual-process signal detection model predictions and findings (e.g., Macken, 2002; Parks & Yonelinas, 2008), recollection sensitivity, but not familiarity sensitivity, was found to be local EC dependent. However, local EC dependent recognition was observed only after item-specific encoding instructions, irrespective of stimulus presentation. These findings and the existing literature suggest that the use of single word presentations and item-specific encoding enhances local EC dependent recognition.

Optical image encryption method based on incoherent imaging and polarized light encoding

Science.gov (United States)

Wang, Q.; Xiong, D.; Alfalou, A.; Brosseau, C.

2018-05-01

We propose an incoherent encoding system for image encryption based on a polarized encoding method combined with an incoherent imaging. Incoherent imaging is the core component of this proposal, in which the incoherent point-spread function (PSF) of the imaging system serves as the main key to encode the input intensity distribution thanks to a convolution operation. An array of retarders and polarizers is placed on the input plane of the imaging structure to encrypt the polarized state of light based on Mueller polarization calculus. The proposal makes full use of randomness of polarization parameters and incoherent PSF so that a multidimensional key space is generated to deal with illegal attacks. Mueller polarization calculus and incoherent illumination of imaging structure ensure that only intensity information is manipulated. Another key advantage is that complicated processing and recording related to a complex-valued signal are avoided. The encoded information is just an intensity distribution, which is advantageous for data storage and transition because information expansion accompanying conventional encryption methods is also avoided. The decryption procedure can be performed digitally or using optoelectronic devices. Numerical simulation tests demonstrate the validity of the proposed scheme.

Developing a hippocampal neural prosthetic to facilitate human memory encoding and recall

Science.gov (United States)

Hampson, Robert E.; Song, Dong; Robinson, Brian S.; Fetterhoff, Dustin; Dakos, Alexander S.; Roeder, Brent M.; She, Xiwei; Wicks, Robert T.; Witcher, Mark R.; Couture, Daniel E.; Laxton, Adrian W.; Munger-Clary, Heidi; Popli, Gautam; Sollman, Myriam J.; Whitlow, Christopher T.; Marmarelis, Vasilis Z.; Berger, Theodore W.; Deadwyler, Sam A.

2018-06-01

Objective. We demonstrate here the first successful implementation in humans of a proof-of-concept system for restoring and improving memory function via facilitation of memory encoding using the patient’s own hippocampal spatiotemporal neural codes for memory. Memory in humans is subject to disruption by drugs, disease and brain injury, yet previous attempts to restore or rescue memory function in humans typically involved only nonspecific, modulation of brain areas and neural systems related to memory retrieval. Approach. We have constructed a model of processes by which the hippocampus encodes memory items via spatiotemporal firing of neural ensembles that underlie the successful encoding of short-term memory. A nonlinear multi-input, multi-output (MIMO) model of hippocampal CA3 and CA1 neural firing is computed that predicts activation patterns of CA1 neurons during the encoding (sample) phase of a delayed match-to-sample (DMS) human short-term memory task. Main results. MIMO model-derived electrical stimulation delivered to the same CA1 locations during the sample phase of DMS trials facilitated short-term/working memory by 37% during the task. Longer term memory retention was also tested in the same human subjects with a delayed recognition (DR) task that utilized images from the DMS task, along with images that were not from the task. Across the subjects, the stimulated trials exhibited significant improvement (35%) in both short-term and long-term retention of visual information. Significance. These results demonstrate the facilitation of memory encoding which is an important feature for the construction of an implantable neural prosthetic to improve human memory.

Biomolecule-to-fluorescent-color encoder: modulation of fluorescence emission via DNA structural changes

Science.gov (United States)

Nishimura, Takahiro; Ogura, Yusuke; Yamada, Kenji; Ohno, Yuko; Tanida, Jun

2014-01-01

A biomolecule-to-fluorescent-color (B/F) encoder for optical readout of biomolecular information is proposed. In the B/F encoder, a set of fluorescence wavelengths and their intensity levels are used for coding of a biomolecular signal. A hybridization chain reaction of hairpin DNAs labeled with fluorescent reporters was performed to generate the fluorescence color codes. The fluorescence is modulated via fluorescence resonance energy transfer, which is controlled by DNA structural changes. The results demonstrate that fluorescent color codes can be configured based on two wavelengths and five intensities using the B/F encoder, and the assigned codes can be retrieved via fluorescence measurements. PMID:25071950

Distinct medial temporal networks encode surprise during motivation by reward versus punishment

OpenAIRE

Murty, Vishnu P.; LaBar, Kevin S.; Adcock, R. Alison

2016-01-01

Adaptive motivated behavior requires predictive internal representations of the environment, and surprising events are indications for encoding new representations of the environment. The medial temporal lobe memory system, including the hippocampus and surrounding cortex, encodes surprising events and is influenced by motivational state. Because behavior reflects the goals of an individual, we investigated whether motivational valence (i.e., pursuing rewards versus avoiding punishments) also...

Effect of phase-encoding direction on group analysis of resting-state functional magnetic resonance imaging.

Science.gov (United States)

Mori, Yasuo; Miyata, Jun; Isobe, Masanori; Son, Shuraku; Yoshihara, Yujiro; Aso, Toshihiko; Kouchiyama, Takanori; Murai, Toshiya; Takahashi, Hidehiko

2018-05-17

Echo-planar imaging is a common technique used in functional magnetic resonance imaging (fMRI), however it suffers from image distortion and signal loss because of large susceptibility effects that are related to the phase-encoding direction of the scan. Despite this relationship, the majority of neuroimaging studies have not considered the influence of phase-encoding direction. Here, we aimed to clarify how phase-encoding direction can affect the outcome of an fMRI connectivity study of schizophrenia. Resting-state fMRI using anterior to posterior (A-P) and posterior to anterior (P-A) directions was used to examine 25 patients with schizophrenia (SC) and 37 matched healthy controls (HC). We conducted a functional connectivity analysis using independent component analysis and performed three group comparisons: A-P vs. P-A (all participants), SC vs. HC for the A-P and P-A datasets, and the interaction between phase-encoding direction and participant group. The estimated functional connectivity differed between the two phase-encoding directions in areas that were more extensive than those where signal loss has been reported. Although functional connectivity in the SC group was lower than that in the HC group for both directions, the A-P and P-A conditions did not exhibit the same specific pattern of differences. Further, we observed an interaction between participant group and the phase-encoding direction in the left temporo-parietal junction and left fusiform gyrus. Phase-encoding direction can influence the results of functional connectivity studies. Thus, appropriate selection and documentation of phase-encoding direction will be important in future resting-state fMRI studies. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Method for making an improved magnetic encoding device

Science.gov (United States)

Fox, Richard J.

1981-01-01

A magnetic encoding device and method for making the same are provided for use as magnetic storage mediums in identification control applications which give output signals from a reader that are of shorter duration and substantially greater magnitude than those of the prior art. Magnetic encoding elements are produced by uniformly bending wire or strip stock of a magnetic material longitudinally about a common radius to exceed the elastic limit of the material and subsequently mounting the material so that it is restrained in an unbent position on a substrate of nonmagnetic material. The elements are spot weld attached to a substrate to form a binary coded array of elements according to a desired binary code. The coded substrate may be enclosed in a plastic laminate structure. Such devices may be used for security badges, key cards, and the like and may have many other applications.

Improvement of encoding and retrieval in normal and pathological aging with word-picture paradigm.

Science.gov (United States)

Iodice, Rosario; Meilán, Juan José G; Carro, Juan

2015-01-01

During the aging process, there is a progressive deficit in the encoding of new information and its retrieval. Different strategies are used in order to maintain, optimize or diminish these deficits in people with and without dementia. One of the classic techniques is paired-associate learning (PAL), which is based on improving the encoding of memories, but it has yet to be used to its full potential in people with dementia. In this study, our aim is to corroborate the importance of PAL tasks as instrumental tools for creating contextual cues, during both the encoding and retrieval phases of memory. Additionally, we aim to identify the most effective form of presenting the related items. Pairs of stimuli were shown to healthy elderly people and to patients with moderate and mild Alzheimer's disease. The encoding conditions were as follows: word/word, picture/picture, picture/word, and word/picture. Associative cued recall of the second item in the pair shows that retrieval is higher for the word/picture condition in the two groups of patients with dementia when compared to the other conditions, while word/word is the least effective in all cases. These results confirm that PAL is an effective tool for creating contextual cues during both the encoding and retrieval phases in people with dementia when the items are presented using the word/picture condition. In this way, the encoding and retrieval deficit can be reduced in these people.

Semantic encoding and retrieval in the left inferior prefrontal cortex: a functional MRI study of task difficulty and process specificity.

Science.gov (United States)

Demb, J B; Desmond, J E; Wagner, A D; Vaidya, C J; Glover, G H; Gabrieli, J D

1995-09-01

Prefrontal cortical function was examined during semantic encoding and repetition priming using functional magnetic resonance imaging (fMRI), a noninvasive technique for localizing regional changes in blood oxygenation, a correlate of neural activity. Words studied in a semantic (deep) encoding condition were better remembered than words studied in both easier and more difficult nonsemantic (shallow) encoding conditions, with difficulty indexed by response time. The left inferior prefrontal cortex (LIPC) (Brodmann's areas 45, 46, 47) showed increased activation during semantic encoding relative to nonsemantic encoding regardless of the relative difficulty of the nonsemantic encoding task. Therefore, LIPC activation appears to be related to semantic encoding and not task difficulty. Semantic encoding decisions are performed faster the second time words are presented. This represents semantic repetition priming, a facilitation in semantic processing for previously encoded words that is not dependent on intentional recollection. The same LIPC area activated during semantic encoding showed decreased activation during repeated semantic encoding relative to initial semantic encoding of the same words. This decrease in activation during repeated encoding was process specific; it occurred when words were semantically reprocessed but not when words were nonsemantically reprocessed. The results were apparent in both individual and averaged functional maps. These findings suggest that the LIPC is part of a semantic executive system that contributes to the on-line retrieval of semantic information.

Modality-specific alpha modulations facilitate long-term memory encoding in the presence of distracters.

Science.gov (United States)

Jiang, Haiteng; van Gerven, Marcel A J; Jensen, Ole

2015-03-01

It has been proposed that long-term memory encoding is not only dependent on engaging task-relevant regions but also on disengaging task-irrelevant regions. In particular, oscillatory alpha activity has been shown to be involved in shaping the functional architecture of the working brain because it reflects the functional disengagement of specific regions in attention and memory tasks. We here ask if such allocation of resources by alpha oscillations generalizes to long-term memory encoding in a cross-modal setting in which we acquired the ongoing brain activity using magnetoencephalography. Participants were asked to encode pictures while ignoring simultaneously presented words and vice versa. We quantified the brain activity during rehearsal reflecting subsequent memory in the different attention conditions. The key finding was that successful long-term memory encoding is reflected by alpha power decreases in the sensory region of the to-be-attended modality and increases in the sensory region of the to-be-ignored modality to suppress distraction during rehearsal period. Our results corroborate related findings from attention studies by demonstrating that alpha activity is also important for the allocation of resources during long-term memory encoding in the presence of distracters.

Neural activation patterns of successful episodic encoding: Reorganization during childhood, maintenance in old age

Directory of Open Access Journals (Sweden)

Yee Lee Shing

2016-08-01

Full Text Available The two-component framework of episodic memory (EM development posits that the contributions of medial temporal lobe (MTL and prefrontal cortex (PFC to successful encoding differ across the lifespan. To test the framework’s hypotheses, we compared subsequent memory effects (SME of 10–12 year-old children, younger adults, and older adults using functional magnetic resonance imaging (fMRI. Memory was probed by cued recall, and SME were defined as regional activation differences during encoding between subsequently correctly recalled versus omitted items. In MTL areas, children’s SME did not differ in magnitude from those of younger and older adults. In contrast, children’s SME in PFC were weaker than the corresponding SME in younger and older adults, in line with the hypothesis that PFC contributes less to successful encoding in childhood. Differences in SME between younger and older adults were negligible. The present results suggest that, among individuals with high memory functioning, the neural circuitry contributing to successful episodic encoding is reorganized from middle childhood to adulthood. Successful episodic encoding in later adulthood, however, is characterized by the ability to maintain the activation patterns that emerged in young adulthood.

Grapheme-color synesthesia can enhance immediate memory without disrupting the encoding of relational cues.

Science.gov (United States)

Gibson, Bradley S; Radvansky, Gabriel A; Johnson, Ann C; McNerney, M Windy

2012-12-01

Previous evidence has suggested that grapheme-color synesthesia can enhance memory for words, but little is known about how these photisms cue retrieval. Often, the encoding of specific features of individual words can disrupt the encoding of ordered relations between words, resulting in an overall decrease in recall accuracy. Here we show that the photisms arising from grapheme-color synesthesia do not function like these item-specific cues. The influences of high and low word frequency on the encoding of ordered relations and the accuracy of immediate free recall were compared across a group of 10 synesthetes and 48 nonsynesthetes. The main findings of Experiment 1 showed that the experience of synesthesia had no adverse effect on the encoding of ordered relations (as measured by input-output correspondence); furthermore, it enhanced recall accuracy in a strictly additive fashion across the two word frequency conditions. Experiment 2 corroborated these findings by showing that the synesthetes only outperformed the nonsynesthetes when the materials involved words and letters, not when they involved digits and spatial locations. Altogether, the present findings suggest that synesthesia can boost immediate memory performance without disrupting the encoding of ordered relations.

Semantic Encoding Enhances the Pictorial Superiority Effect in the Oldest-Old

Science.gov (United States)

Cherry, Katie E.; Brown, Jennifer Silva; Walker, Erin Jackson; Smitherman, Emily A.; Boudreaux, Emily O.; Volaufova, Julia; Jazwinski, S. Michal

2011-01-01

We examined the effect of a semantic orienting task during encoding on free recall and recognition of simple line drawings and matching words in middle-aged (44 to 59 years), older (60 to 89 years), and oldest-old (90 + years) adults. Participants studied line drawings and matching words presented in blocked order. Half of the participants were given a semantic orienting task and the other half received standard intentional learning instructions. Results confirmed that the pictorial superiority effect was greater in magnitude following semantic encoding compared to the control condition. Analyses of clustering in free recall revealed that oldest-old adults’ encoding and retrieval strategies were generally similar to the two younger groups. Self-reported strategy use was less frequent among the oldest-old adults. These data strongly suggest that semantic elaboration is an effective compensatory mechanism underlying preserved episodic memory performance that persists well into the ninth decade of life. PMID:22053814

Method and system for progressive mesh storage and reconstruction using wavelet-encoded height fields

Science.gov (United States)

Baxes, Gregory A. (Inventor); Linger, Timothy C. (Inventor)

2011-01-01

Systems and methods are provided for progressive mesh storage and reconstruction using wavelet-encoded height fields. A method for progressive mesh storage includes reading raster height field data, and processing the raster height field data with a discrete wavelet transform to generate wavelet-encoded height fields. In another embodiment, a method for progressive mesh storage includes reading texture map data, and processing the texture map data with a discrete wavelet transform to generate wavelet-encoded texture map fields. A method for reconstructing a progressive mesh from wavelet-encoded height field data includes determining terrain blocks, and a level of detail required for each terrain block, based upon a viewpoint. Triangle strip constructs are generated from vertices of the terrain blocks, and an image is rendered utilizing the triangle strip constructs. Software products that implement these methods are provided.

Feasibility study of a real-time operating system for a multichannel MPEG-4 encoder

Science.gov (United States)

Lehtoranta, Olli; Hamalainen, Timo D.

2005-03-01

Feasibility of DSP/BIOS real-time operating system for a multi-channel MPEG-4 encoder is studied. Performances of two MPEG-4 encoder implementations with and without the operating system are compared in terms of encoding frame rate and memory requirements. The effects of task switching frequency and number of parallel video channels to the encoding frame rate are measured. The research is carried out on a 200 MHz TMS320C6201 fixed point DSP using QCIF (176x144 pixels) video format. Compared to a traditional DSP implementation without an operating system, inclusion of DSP/BIOS reduces total system throughput only by 1 QCIF frames/s. The operating system has 6 KB data memory overhead and program memory requirement of 15.7 KB. Hence, the overhead is considered low enough for resource critical mobile video applications.

Divided Attention Can Enhance Memory Encoding: The Attentional Boost Effect in Implicit Memory

Science.gov (United States)

Spataro, Pietro; Mulligan, Neil W.; Rossi-Arnaud, Clelia

2013-01-01

Distraction during encoding has long been known to disrupt later memory performance. Contrary to this long-standing result, we show that detecting an infrequent target in a dual-task paradigm actually improves memory encoding for a concurrently presented word, above and beyond the performance reached in the full-attention condition. This absolute…

A Ti plasmid-encoded enzyme required for degradation of mannopine is functionally homologous to the T-region-encoded enzyme required for synthesis of this opine in crown gall tumors.

Science.gov (United States)

Kim, K S; Chilton, W S; Farrand, S K

1996-06-01

The mocC gene encoded by the octopine/mannityl opine-type Ti plasmid pTi15955 is related at the nucleotide sequence level to mas1' encoded by the T region of this plasmid. While Mas1 is required for the synthesis of mannopine (MOP) by crown gall tumor cells, MocC is essential for the utilization of MOP by Agrobacterium spp. A cosmid clone of pTi15955, pYDH208, encodes mocC and confers the utilization of MOP on strain NT1 and on strain UIA5, a derivative of NT1 lacking the 450-kb cryptic plasmid pAtC58. NT1 or UIA5 harboring pYDH208 with an insertion mutation in mocC failed to utilize MOP as the sole carbon source. Plasmid pSa-C, which encodes only mocC, complemented this mutation in both strains. This plasmid also was sufficient to confer utilization of MOP on NT1 but not on UIA5. Computer analysis showed that MocC is related at the amino acid sequence level to members of the short-chain alcohol dehydrogenase family of oxidoreductases. Lysates prepared from Escherichia coli cells expressing mocC contained an enzymatic activity that oxidizes MOP to deoxyfructosyl glutamine (santhopine [SOP]) in the presence of NAD+. The reaction catalyzed by the MOP oxidoreductase is reversible; in the presence of NADH, the enzyme reduced SOP to MOP. The apparent Km values of the enzyme for MOP and SOP were 6.3 and 1.2 mM, respectively. Among analogs of MOP tested, only N-1-(1-deoxy-D-lyxityl)-L-glutamine and N-1-(1-deoxy-D-mannityl)-L-asparagine served as substrates for MOP oxidoreductase. These results indicate that mocC encodes an oxidoreductase that, as an oxidase, is essential for the catabolism of MOP. The reductase activity of this enzyme is precisely the reaction ascribed to its T-region-encoded homolog, Mas1, which is responsible for biosynthesis of mannopine in crown gall tumors.

Resource-aware complexity scalability for mobile MPEG encoding

NARCIS (Netherlands)

Mietens, S.O.; With, de P.H.N.; Hentschel, C.; Panchanatan, S.; Vasudev, B.

2004-01-01

Complexity scalability attempts to scale the required resources of an algorithm with the chose quality settings, in order to broaden the application range. In this paper, we present complexity-scalable MPEG encoding of which the core processing modules are modified for scalability. Scalability is

EGVII endoglucanase and nucleic acids encoding the same

Science.gov (United States)

Dunn-Coleman, Nigel [Los Gatos, CA; Goedegebuur, Frits [Vlaardingen, NL; Ward, Michael [San Francisco, CA; Yao, Jian [Sunnyvale, CA

2009-05-05

The present invention provides an endoglucanase nucleic acid sequence, designated egl7, and the corresponding EGVII amino acid sequence. The invention also provides expression vectors and host cells comprising a nucleic acid sequence encoding EGVII, recombinant EGVII proteins and methods for producing the same.