The actin-binding proteins eps8 and gelsolin have complementary roles in regulating the growth and stability of mechanosensory hair bundles of mammalian cochlear outer hair cells.

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Jennifer Olt

Full Text Available Sound transduction depends upon mechanosensitive channels localized on the hair-like bundles that project from the apical surface of cochlear hair cells. Hair bundles show a stair-case structure composed of rows of stereocilia, and each stereocilium contains a core of tightly-packed and uniformly-polarized actin filaments. The growth and maintenance of the stereociliary actin core are dynamically regulated. Recently, it was shown that the actin-binding protein gelsolin is expressed in the stereocilia of outer hair cells (OHCs and in its absence they become long and straggly. Gelsolin is part of a whirlin scaffolding protein complex at the stereocilia tip, which has been shown to interact with other actin regulatory molecules such as Eps8. Here we investigated the physiological effects associated with the absence of gelsolin and its possible overlapping role with Eps8. We found that, in contrast to Eps8, gelsolin does not affect mechanoelectrical transduction during immature stages of development. Moreover, OHCs from gelsolin knockout mice were able to mature into fully functional sensory receptors as judged by the normal resting membrane potential and basolateral membrane currents. Mechanoelectrical transducer current in gelsolin-Eps8 double knockout mice showed a profile similar to that observed in the single mutants for Eps8. We propose that gelsolin has a non-overlapping role with Eps8. While Eps8 is mainly involved in the initial growth of stereocilia in both inner hair cells (IHCs and OHCs, gelsolin is required for the maintenance of mature hair bundles of low-frequency OHCs after the onset of hearing.

Correlation between Platelet Gelsolin and Platelet Activation Level in Acute Myocardial Infarction Rats and Intervention Effect of Effective Components of Chuanxiong Rhizome and Red Peony Root

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Yue Liu

2013-01-01

Full Text Available The biological role of platelet gelsolin in platelet activation of acute myocardial infarction is not defined. In order to provide a potential new antiplatelet target for Chinese medicine and to elucidate the contribution of Xiongshao capsule, the effective components of Chuanxiong rhizome and red peony root, in this study, we randomly allocated Sprague Dawley rats to left anterior descending coronary artery ligation or sham surgery and different drug prophylaxis as control. We found that gelsolin is highly expressed in platelet rich plasma and lowly expressed in platelet poor plasma, accompanied by the high platelet activation level in model rats; plasma actin filaments and mean fluorescence intensity (MFI of platelet calcium ion increased and plasma vitamin D binding protein decreased in model rats. Xiongshao capsule could inhibit the gelsolin expression in platelet rich plasma and ischemic heart tissue simultaneously and reduce the level of plasma F-actin and MFI of platelet calcium ion. Our study concludes that platelet gelsolin is an important contributor to platelet activation, and platelet gelsolin inhibition may form a novel target for antiplatelet therapy. Xiongshao capsule may be a promising Chinese medicine drug for antiplatelet and aspirin-like cardioprotection effect.

Expected packing density allows prediction of both amyloidogenic and disordered regions in protein chains

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Galzitskaya, Oxana V; Garbuzynskiy, Sergiy O; Lobanov, Michail Yu [Institute of Protein Research, Russian Academy of Sciences, 142290, Pushchino, Moscow Region (Russian Federation)

2007-07-18

The determination of factors that influence conformational changes in proteins is very important for the identification of potentially amyloidogenic and disordered regions in polypeptide chains. In our work we introduce a new parameter, mean packing density, to detect both amyloidogenic and disordered regions in a protein sequence. It has been shown that regions with strong expected packing density are responsible for amyloid formation. Our predictions are consistent with known disease-related amyloidogenic regions for 9 of 12 amyloid-forming proteins and peptides in which the positions of amyloidogenic regions have been revealed experimentally. Our findings support the concept that the mechanism of formation of amyloid fibrils is similar for different peptides and proteins. Moreover, we have demonstrated that regions with weak expected packing density are responsible for the appearance of disordered regions. Our method has been tested on datasets of globular proteins and long disordered protein segments, and it shows improved performance over other widely used methods. Thus, we demonstrate that the expected packing density is a useful value for predicting both disordered and amyloidogenic regions of a protein based on sequence alone. Our results are important for understanding the structural characteristics of protein folding and misfolding.

EGCG Inhibited Lipofuscin Formation Based on Intercepting Amyloidogenic β-Sheet-Rich Structure Conversion.

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Shuxian Cai

Full Text Available Lipofuscin (LF is formed during lipid peroxidation and sugar glycosylation by carbonyl-amino crosslinks with biomacrolecules, and accumulates slowly within postmitotic cells. The environmental pollution, modern dietary culture and lifestyle changes have been found to be the major sources of reactive carbonyl compounds in vivo. Irreversible carbonyl-amino crosslinks induced by carbonyl stress are essentially toxiferous for aging-related functional losses in modern society. Results show that (--epigallocatechin gallate (EGCG, the main polyphenol in green tea, can neutralize the carbonyl-amino cross-linking reaction and inhibit LF formation, but the underlying mechanism is unknown.We explored the mechanism of the neutralization process from protein, cell, and animal levels using spectrofluorometry, infrared spectroscopy, conformation antibodies, and electron microscopy. LF demonstrated an amyloidogenic β-sheet-rich with antiparallel structure, which accelerated the carbonyl-amino crosslinks formation and disrupted proteolysis in both PC12 cells and D-galactose (D-gal-induced brain aging mice models. Additionally, EGCG effectively inhibited the formation of the amyloidogenic β-sheet-rich structure of LF, and prevented its conversion into toxic and on-pathway aggregation intermediates, thereby cutting off the carbonyl-amino crosslinks.Our study indicated that the amyloidogenic β-sheet structure of LF may be the core driving force for carbonyl-amino crosslinks further formation, which mediates the formation of amyloid fibrils from native state of biomacrolecules. That EGCG exhibits anti-amyloidogenic β-sheet-rich structure properties to prevent the LF formation represents a novel strategy to impede the development of degenerative processes caused by ageing or stress-induced premature senescence in modern environments.

Plasma Gelsolin Promotes Proliferation of Mesangial Cell in IgA Nephropathy

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Lei Zhang

2016-12-01

Full Text Available Background/Aims: Plasma gelsolin (pGSN is an actin-binding protein that plays a critical role in the pathogenesis of rheumatoid arthritis. However, whether pGSN is involved in other immunological diseases remains unknown. This study focused on the relationship between pGSN and immunoglobulin A (IgA nephropathy (IgAN. Methods: Two hundred patients with IgAN, 200 patients each with several other types of nephropathy and healthy controls (HCs who underwent kidney biopsies between 2000 and 2014 were enrolled in the study. The Oxford classification system was used to predict the risk of disease progression. Serum and renal tissue were used to detect pGSN, and the correlations between pGSN and IgA, galactose-deficient IgA1 (Gd-IgA1, transforming growth factor beta1 (TGF-β1, fibronectin (FN content, clinical symptoms, and kidney function were analyzed. Results: We found that the pGSN levels were significantly decreased in sera from IgAN patients compared to sera from patients with other forms of glomerular nephritis and HCs. Furthermore, the serum pGSN levels were negatively correlated with the serum IgA1, FN, and TGF-β1 levels, and positively correlated with the estimated glomerular filtration rate. Conversely, the glomerular pGSN content was significantly elevated in the IgAN patients and was positively correlated with TGF-β1 and FN levels. In renal tissue, the pGSN levels were significantly higher in IgAN patients with M1 and S1 compared to patients with M0 and S0 (p in vitro. pGSN also promoted integrin α2β1 expression in HMCs and enhanced the integrin α2β1-pGSN interaction. Conclusion: Our study suggested that pGSN may play an important role in the development of IgAN by promoting the proliferation of mesangial cells and that serum and glomerular pGSN levels may be new markers for predicting IgAN progression and prognosis.

Gelsolin negatively regulates the activity of tumor suppressor p53 through their physical interaction in hepatocarcinoma HepG2 cells

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An, Joo-Hee; Kim, Jung-Woong; Jang, Sang-Min; Kim, Chul-Hong; Kang, Eun-Jin; Choi, Kyung-Hee

2011-01-01

Highlights: → The actin binding protein Gelsolin (GSN) interacts with transcription factor p53. → GSN interacts with transactivation- and DNA binding domains of p53. → GSN represses transactivity of p53 via inhibition of nuclear translocation of p53. → GSN inhibits the p53-mediated apoptosis in hepatocarcinoma HepG2 cells. -- Abstract: As a transcription factor, p53 modulates several cellular responses including cell-cycle control, apoptosis, and differentiation. In this study, we have shown that an actin regulatory protein, gelsolin (GSN), can physically interact with p53. The nuclear localization of p53 is inhibited by GSN overexpression in hepatocarcinoma HepG2 cells. Additionally, we demonstrate that GSN negatively regulates p53-dependent transcriptional activity of a reporter construct, driven by the p21-promoter. Furthermore, p53-mediated apoptosis was repressed in GSN-transfected HepG2 cells. Taken together, these results suggest that GSN binds to p53 and this interaction leads to the inhibition of p53-induced apoptosis by anchoring of p53 in the cytoplasm in HepG2 cells.

Clinical significance of gelsolin-like actin-capping protein expression in oral carcinogenesis: an immunohistochemical study of premalignant and malignant lesions of the oral cavity

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Nomura, Hitomi; Kubosawa, Hitoshi; Tanzawa, Hideki; Uzawa, Katsuhiro; Ishigami, Takashi; Kouzu, Yukinao; Koike, Hirofumi; Ogawara, Katsunori; Siiba, Masashi; Bukawa, Hiroki; Yokoe, Hidetaka

2008-01-01

Gelsolin-like actin-capping protein (CapG) is a ubiquitous gelsolin-family actin-modulating protein involved in cell signalling, receptor-mediated membrane ruffling, phagocytosis, and motility. CapG has generated great interest due to its oncogenic function in the control of cell migration or invasion in a variety of cancer cells. We previously applied proteomic methods to characterize differentially expressed proteins in oral squamous-cell carcinoma (OSCC) cells and detected significantly high expression levels of CapG in OSCC-derived cell lines compared to human normal oral keratinocytes. In the current study, to further determine the potential involvement of CapG in OSCC, we evaluated the status of CapG protein and mRNA expression in human oral premalignant lesions (OPLs) and primary OSCCs and correlated the results with clinicopathologic variables. Matched normal and tumour tissue sections of 79 human primary OSCCs and 28 OPLs were analyzed for CapG expression by immunohistochemistry (IHC). Correlations between CapG-immunohistochemical staining scores of OSCCs and clinicopathologic features were evaluated by Fisher's exact test. Real-time quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) was used to estimate CapG expression at the mRNA level. In IHC, substantial up-regulation of CapG protein was observed in primary OSCCs (52%) and OPLs (64%), whereas corresponding normal tissues showed consistently weak or absent immunoreactivity of CapG. qRT-PCR data were consistent with the protein expression status. Moreover, CapG expression was correlated with the TNM stage grading of OSCCs. Our finding of frequent dysregulated expression of CapG in premalignant and malignant lesions together with an association with an advanced clinical disease stage suggests that CapG could contribute to cancer development and progression and that CapG may have potential as a biomarker and a therapeutic target for OSCC

Murine Adseverin (D5), a Novel Member of the Gelsolin Family, and Murine Adseverin Are Induced by Interleukin-9 in T-Helper Lymphocytes

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Robbens, Johan; Louahed, Jamila; De Pestel, Kathleen; Van Colen, Inge; Ampe, Christophe; Vandekerckhove, Joel; Renauld, Jean-Christophe

1998-01-01

We identified a number of upregulated genes by differential screening of interleukin-9-stimulated T-helper lymphocytes. Interestingly, two of these messengers encode proteins that are similar to proteins of the gelsolin family. The first displays a typical structure of six homologous domains and shows a high level of identity (90%) with bovine adseverin (or scinderin) and may therefore be considered the murine adseverin homolog. The second encodes a protein with only five segments. Sequence comparison shows that most of the fifth segment and a short amino-terminal part of the sixth segment (amino acids 528 to 628 of adseverin) are missing, and thus, this form may represent an alternatively spliced product derived from the same gene. The corresponding protein is called mouse adseverin (D5). We expressed both proteins in Escherichia coli and show that mouse adseverin displays the typical characteristics of all members of the gelsolin family with respect to actin binding (capping, severing, and nucleation) and its regulation by Ca2+. In contrast, mouse adseverin (D5) fails to nucleate actin polymerization, although like mouse adseverin and gelsolin, it severs and caps actin filaments in a Ca2+-dependent manner. Adseverin is present in all of the tissues and most of the cell lines tested, although at low concentrations. Mouse adseverin (D5) was found only in blood cells and in cell lines derived from T-helper lymphocytes and mast cells, where it is weakly expressed. In a gel filtration experiment, we demonstrated that mouse adseverin forms a 1:2 complex with G actin which is stable only in the presence of Ca2+, while no stable complex was observed for mouse adseverin (D5). PMID:9671468

In silico and in vitro characterization of anti-amyloidogenic activity of vitamin K3 analogues for Alzheimer's disease.

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Huy, Pham Dinh Quoc; Yu, Yao-Chung; Ngo, Son Tung; Thao, Tran Van; Chen, Chin-Piao; Li, Mai Suan; Chen, Yi-Cheng

2013-04-01

Aggregation of amyloid-beta (Aβ) has been proposed as the main cause of Alzheimer's disease (AD). Vitamin K deficiency has been linked to the pathogenesis of AD. Therefore, 15 synthesized vitamin K3 (VK3) analogues were studied for their anti-amyloidogenic activity. Biological and spectroscopic assays were used to characterize the effect of VK3 analogues on amyloidogenic properties of Aβ, such as aggregation, free radical formation, and cell viability. Molecular dynamics simulation was used to calculate the binding affinity and mode of VK3 analogue binding to Aβ. Both numerical and experimental results showed that several VK3 analogues, including VK3-6, VK3-8, VK3-9, VK3-10, and VK3-224 could effectively inhibit Aβ aggregation and conformational conversion. The calculated inhibition constants were in the μM range for VK3-10, VK3-6, and VK3-9 which was similar to the IC50 of curcumin. Cell viability assays indicated that VK3-9 could effectively reduce free radicals and had a protective effect on cytotoxicity induced by Aβ. The results clearly demonstrated that VK3 analogues could effectively inhibit Aβ aggregation and protect cells against Aβ induced toxicity. Modified VK3 analogues can possibly be developed as effective anti-amyloidogenic drugs for the treatment of AD. VK3 analogues effectively inhibit Aβ aggregation and are highly potent as anti-amyloidogenic drugs for therapeutic treatment of AD. Copyright © 2012 Elsevier B.V. All rights reserved.

Estrogen has anti-amyloidogenic effects on Alzheimer's β-amyloid fibrils in vitro

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Morinaga, Akiyoshi; Hirohata, Mie; Ono, Kenjiro; Yamada, Masahito

2007-01-01

Inhibition of the assembly of amyloid β-peptide (Aβ) as well as the destabilization of preformed β-amyloid fibrils (fAβ) in the central nervous system could be valuable therapeutics of patients with Alzheimer's disease (AD). Epidemiological studies have indicated that estrogen therapy reduced the risk of developing AD in women. Here, we examined the effects of estrogen (estrone (E1), estradiol (E2), and estriol (E3)) and related sexual steroids (androstenedione (AND) and testosterone (TES)) on the polymerization, extension and destabilization of fAβ(1-42) and fAβ(1-40) at pH 7.5 at 37 o C in vitro, using fluorescence spectroscopic analysis with thioflavin T and electron microscopic studies. E1, E2, and E3 dose-dependently inhibited the formation, as well as destabilization of fAβs. The overall anti-amyloidogenic activity of these molecules was in the order of: E3 > E2 = E1 >>AND = TES. Estrogen could be a potential therapeutic agent to prevent or delay AD progression

Disrupting self-assembly and toxicity of amyloidogenic protein oligomers by "molecular tweezers" - from the test tube to animal models.

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Attar, Aida; Bitan, Gal

2014-01-01

Despite decades of research, therapy for diseases caused by abnormal protein folding and aggregation (amyloidoses) is limited to treatment of symptoms and provides only temporary and moderate relief to sufferers. The failure in developing successful disease-modifying drugs for amyloidoses stems from the nature of the targets for such drugs - primarily oligomers of amyloidogenic proteins, which are distinct from traditional targets, such as enzymes or receptors. The oligomers are metastable, do not have well-defined structures, and exist in dynamically changing mixtures. Therefore, inhibiting the formation and toxicity of these oligomers likely will require out-of-the-box thinking and novel strategies. We review here the development of a strategy based on targeting the combination of hydrophobic and electrostatic interactions that are key to the assembly and toxicity of amyloidogenic proteins using lysine (K)-specific "molecular tweezers" (MTs). Our discussion includes a survey of the literature demonstrating the important role of K residues in the assembly and toxicity of amyloidogenic proteins and the development of a lead MT derivative called CLR01, from an inhibitor of protein aggregation in vitro to a drug candidate showing effective amelioration of disease symptoms in animal models of Alzheimer's and Parkinson's diseases.

Quantitative modelling of amyloidogenic processing and its influence by SORLA in Alzheimer's disease.

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Schmidt, Vanessa; Baum, Katharina; Lao, Angelyn; Rateitschak, Katja; Schmitz, Yvonne; Teichmann, Anke; Wiesner, Burkhard; Petersen, Claus Munck; Nykjaer, Anders; Wolf, Jana; Wolkenhauer, Olaf; Willnow, Thomas E

2012-01-04

The extent of proteolytic processing of the amyloid precursor protein (APP) into neurotoxic amyloid-β (Aβ) peptides is central to the pathology of Alzheimer's disease (AD). Accordingly, modifiers that increase Aβ production rates are risk factors in the sporadic form of AD. In a novel systems biology approach, we combined quantitative biochemical studies with mathematical modelling to establish a kinetic model of amyloidogenic processing, and to evaluate the influence by SORLA/SORL1, an inhibitor of APP processing and important genetic risk factor. Contrary to previous hypotheses, our studies demonstrate that secretases represent allosteric enzymes that require cooperativity by APP oligomerization for efficient processing. Cooperativity enables swift adaptive changes in secretase activity with even small alterations in APP concentration. We also show that SORLA prevents APP oligomerization both in cultured cells and in the brain in vivo, eliminating the preferred form of the substrate and causing secretases to switch to a less efficient non-allosteric mode of action. These data represent the first mathematical description of the contribution of genetic risk factors to AD substantiating the relevance of subtle changes in SORLA levels for amyloidogenic processing as proposed for patients carrying SORL1 risk alleles.

Plasma Gelsolin Induced Glomerular Fibrosis via the TGF-β1/Smads Signal Transduction Pathway in IgA Nephropathy

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Lei Zhang

2017-02-01

Full Text Available Glomerular fibrosis has been shown to be closely related to the progression and prognosis of IgA nephropathy (IgAN. However, mechanism underlying IgAN glomerular fibrosis remains unclear. Recently, our study showed that plasma gelsolin (pGSN was decreased in the serum of an IgAN mouse model and that pGSN deposition was found in the glomeruli. Another cytokine, TGF-β1, which is closely related to glomerular fibrosis, was also found to be highly expressed in the glomeruli. In the present study, we report that pGSN induces glomerular fibrosis through the TGF-β1/Smads signal transduction pathway. This is supported by the following findings: human mesangial cells (HMCs show remarkable morphological changes and proliferation in response to co-stimulation with pGSN and polymeric IgA1 (pIgA1 from IgAN patients compared to other controls. Moreover, ELISA assays showed that more TGF-β1 secretion was found in HMCs supernatants in the co-stimulation group. Further experiments showed increased TGF-β1, Smad3, p-Smad2/3, Smad4, and collagen 1 and decreased Smad7 expression in the co-stimulation group. Our present study implied that the synergistic effect of pGSN and pIgA induced glomerular fibrosis via the TGF-β1/Smads signal transduction pathway. This might be a potential mechanism for the glomerular fibrosis observed in IgAN patients.

Plasma Gelsolin Induced Glomerular Fibrosis via the TGF-β1/Smads Signal Transduction Pathway in IgA Nephropathy

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Zhang, Lei; Han, Changsong; Ye, Fei; He, Yan; Jin, Yinji; Wang, Tianzhen; Wu, Yiqi; Jiang, Yang; Zhang, Fengmin; Jin, Xiaoming

2017-01-01

Glomerular fibrosis has been shown to be closely related to the progression and prognosis of IgA nephropathy (IgAN). However, mechanism underlying IgAN glomerular fibrosis remains unclear. Recently, our study showed that plasma gelsolin (pGSN) was decreased in the serum of an IgAN mouse model and that pGSN deposition was found in the glomeruli. Another cytokine, TGF-β1, which is closely related to glomerular fibrosis, was also found to be highly expressed in the glomeruli. In the present study, we report that pGSN induces glomerular fibrosis through the TGF-β1/Smads signal transduction pathway. This is supported by the following findings: human mesangial cells (HMCs) show remarkable morphological changes and proliferation in response to co-stimulation with pGSN and polymeric IgA1 (pIgA1) from IgAN patients compared to other controls. Moreover, ELISA assays showed that more TGF-β1 secretion was found in HMCs supernatants in the co-stimulation group. Further experiments showed increased TGF-β1, Smad3, p-Smad2/3, Smad4, and collagen 1 and decreased Smad7 expression in the co-stimulation group. Our present study implied that the synergistic effect of pGSN and pIgA induced glomerular fibrosis via the TGF-β1/Smads signal transduction pathway. This might be a potential mechanism for the glomerular fibrosis observed in IgAN patients. PMID:28208683

Machine learning methods can replace 3D profile method in classification of amyloidogenic hexapeptides

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Stanislawski Jerzy

2013-01-01

Full Text Available Abstract Background Amyloids are proteins capable of forming fibrils. Many of them underlie serious diseases, like Alzheimer disease. The number of amyloid-associated diseases is constantly increasing. Recent studies indicate that amyloidogenic properties can be associated with short segments of aminoacids, which transform the structure when exposed. A few hundreds of such peptides have been experimentally found. Experimental testing of all possible aminoacid combinations is currently not feasible. Instead, they can be predicted by computational methods. 3D profile is a physicochemical-based method that has generated the most numerous dataset - ZipperDB. However, it is computationally very demanding. Here, we show that dataset generation can be accelerated. Two methods to increase the classification efficiency of amyloidogenic candidates are presented and tested: simplified 3D profile generation and machine learning methods. Results We generated a new dataset of hexapeptides, using more economical 3D profile algorithm, which showed very good classification overlap with ZipperDB (93.5%. The new part of our dataset contains 1779 segments, with 204 classified as amyloidogenic. The dataset of 6-residue sequences with their binary classification, based on the energy of the segment, was applied for training machine learning methods. A separate set of sequences from ZipperDB was used as a test set. The most effective methods were Alternating Decision Tree and Multilayer Perceptron. Both methods obtained area under ROC curve of 0.96, accuracy 91%, true positive rate ca. 78%, and true negative rate 95%. A few other machine learning methods also achieved a good performance. The computational time was reduced from 18-20 CPU-hours (full 3D profile to 0.5 CPU-hours (simplified 3D profile to seconds (machine learning. Conclusions We showed that the simplified profile generation method does not introduce an error with regard to the original method, while

Machine learning methods can replace 3D profile method in classification of amyloidogenic hexapeptides.

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Stanislawski, Jerzy; Kotulska, Malgorzata; Unold, Olgierd

2013-01-17

Amyloids are proteins capable of forming fibrils. Many of them underlie serious diseases, like Alzheimer disease. The number of amyloid-associated diseases is constantly increasing. Recent studies indicate that amyloidogenic properties can be associated with short segments of aminoacids, which transform the structure when exposed. A few hundreds of such peptides have been experimentally found. Experimental testing of all possible aminoacid combinations is currently not feasible. Instead, they can be predicted by computational methods. 3D profile is a physicochemical-based method that has generated the most numerous dataset - ZipperDB. However, it is computationally very demanding. Here, we show that dataset generation can be accelerated. Two methods to increase the classification efficiency of amyloidogenic candidates are presented and tested: simplified 3D profile generation and machine learning methods. We generated a new dataset of hexapeptides, using more economical 3D profile algorithm, which showed very good classification overlap with ZipperDB (93.5%). The new part of our dataset contains 1779 segments, with 204 classified as amyloidogenic. The dataset of 6-residue sequences with their binary classification, based on the energy of the segment, was applied for training machine learning methods. A separate set of sequences from ZipperDB was used as a test set. The most effective methods were Alternating Decision Tree and Multilayer Perceptron. Both methods obtained area under ROC curve of 0.96, accuracy 91%, true positive rate ca. 78%, and true negative rate 95%. A few other machine learning methods also achieved a good performance. The computational time was reduced from 18-20 CPU-hours (full 3D profile) to 0.5 CPU-hours (simplified 3D profile) to seconds (machine learning). We showed that the simplified profile generation method does not introduce an error with regard to the original method, while increasing the computational efficiency. Our new dataset

Nuclear 82-kDa choline acetyltransferase decreases amyloidogenic APP metabolism in neurons from APP/PS1 transgenic mice.

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Albers, Shawn; Inthathirath, Fatima; Gill, Sandeep K; Winick-Ng, Warren; Jaworski, Ewa; Wong, Daisy Y L; Gros, Robert; Rylett, R Jane

2014-09-01

Alzheimer disease (AD) is associated with increased amyloidogenic processing of amyloid precursor protein (APP) to β-amyloid peptides (Aβ), cholinergic neuron loss with decreased choline acetyltransferase (ChAT) activity, and cognitive dysfunction. Both 69-kDa ChAT and 82-kDa ChAT are expressed in cholinergic neurons in human brain and spinal cord with 82-kDa ChAT localized predominantly to neuronal nuclei, suggesting potential alternative functional roles for the enzyme. By gene microarray analysis, we found that 82-kDa ChAT-expressing IMR32 neural cells have altered expression of genes involved in diverse cellular functions. Importantly, genes for several proteins that regulate APP processing along amyloidogenic and non-amyloidogenic pathways are differentially expressed in 82-kDa ChAT-containing cells. The predicted net effect based on observed changes in expression patterns of these genes would be decreased amyloidogenic APP processing with decreased Aβ production. This functional outcome was verified experimentally as a significant decrease in BACE1 protein levels and activity and a concomitant reduction in the release of endogenous Aβ1-42 from neurons cultured from brains of AD-model APP/PS1 transgenic mice. The expression of 82-kDa ChAT in neurons increased levels of GGA3, which is involved in trafficking BACE1 to lysosomes for degradation. shRNA-induced decreases in GGA3 protein levels attenuated the 82-kDa ChAT-mediated decreases in BACE1 protein and activity and Aβ1-42 release. Evidence that 82-kDa ChAT can enhance GGA3 gene expression is shown by enhanced GGA3 gene promoter activity in SN56 neural cells expressing this ChAT protein. These studies indicate a novel relationship between cholinergic neurons and APP processing, with 82-kDa ChAT acting as a negative regulator of Aβ production. This decreased formation of Aβ could result in protection for cholinergic neurons, as well as protection of other cells in the vicinity that are sensitive to

Exploring the structural diversity in inhibitors of α-synuclein amyloidogenic folding, aggregation and neurotoxicity

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Das, Sukanya; Pukala, Tara L.; Smid, Scott D.

2018-05-01

Aggregation of α-Synuclein (αS) protein to amyloid fibrils is a neuropathological hallmark of Parkinson’s disease (PD). Growing evidence suggests that extracellular αS aggregation plays a pivotal role in neurodegeneration found in PD in addition to the intracellular αS aggregates in Lewy bodies (LB). Here, we identified and compared a diverse set of molecules capable of mitigating protein aggregation and exogenous toxicity of αSA53T, a more aggregation-prone αS mutant found in familial PD. For the first time, we investigated the αS anti-amyloid activity of semi-synthetic flavonoid 2', 3', 4' trihydroxyflavone or 2-D08, which was compared with natural flavones myricetin and transilitin, as well as such structurally diverse polyphenols as honokiol and punicalagin. Additionally, two novel synthetic compounds with a dibenzyl imidazolidine scaffold, Compound 1 and Compound 2, were also investigated as they exhibited favourable binding with αSA53T. All seven compounds inhibited αSA53T aggregation as demonstrated by Thioflavin T fluorescence assays, with modified fibril morphology observed by transmission electron microscopy. Ion mobility-mass spectrometry (IM-MS) was used to monitor the structural conversion of native αSA53T into amyloidogenic conformations and all seven compounds preserved the native unfolded conformations of αSA53T following 48 hrs incubation. The presence of each test compound in a 1:2 molar ratio was also shown to inhibit the neurotoxicity of preincubated αSA53T using phaeochromocytoma (PC12) cell viability assays. Among the seven tested compounds 2-D08, honokiol and the synthetic Compound 2 demonstrated the highest inhibition of aggregation, coupled with neuroprotection from preincubated αSA53T in vitro. Molecular docking predicted that all compounds bound near the lysine-rich region of the N-terminus of αSA53T, where the flavonoids and honokiol predominantly interacted with Lys 23. Overall, these findings highlight that i

Use of a Novel Grammatical Inference Approach in Classification of Amyloidogenic Hexapeptides

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Wojciech Wieczorek

2016-01-01

Full Text Available The present paper is a novel contribution to the field of bioinformatics by using grammatical inference in the analysis of data. We developed an algorithm for generating star-free regular expressions which turned out to be good recommendation tools, as they are characterized by a relatively high correlation coefficient between the observed and predicted binary classifications. The experiments have been performed for three datasets of amyloidogenic hexapeptides, and our results are compared with those obtained using the graph approaches, the current state-of-the-art methods in heuristic automata induction, and the support vector machine. The results showed the superior performance of the new grammatical inference algorithm on fixed-length amyloid datasets.

A Redox-Active, Compact Molecule for Cross-Linking Amyloidogenic Peptides into Nontoxic, Off-Pathway Aggregates: In Vitro and In Vivo Efficacy and Molecular Mechanisms

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Derrick, Jeffrey S.; Kerr, Richard A.; Nam, Younwoo; Oh, Shin Bi; Lee, Hyuck Jin; Earnest, Kaylin G.; Suh, Nayoung; Peck, Kristy L.; Ozbil, Mehmet; Korshavn, Kyle J.; Ramamoorthy, Ayyalusamy; Prabhakar, Rajeev; Merino, Edward J.; Shearer, Jason; Lee, Joo-Yong; Ruotolo, Brandon T.; Lim, Mi Hee

2015-11-25

Chemical reagents targeting and controlling amyloidogenic peptides have received much attention for helping identify their roles in the pathogenesis of protein-misfolding disorders. Herein, we report a novel strategy for redirecting amyloidogenic peptides into nontoxic, off-pathway aggregates, which utilizes redox properties of a small molecule (DMPD, N,N-dimethyl-p-phenylenediamine) to trigger covalent adduct formation with the peptide. In addition, for the first time, biochemical, biophysical, and molecular dynamics simulation studies have been performed to demonstrate a mechanistic understanding for such an interaction between a small molecule (DMPD) and amyloid-β (Aβ) and its subsequent anti-amyloidogenic activity, which, upon its transformation, generates ligand–peptide adducts via primary amine-dependent intramolecular cross-linking correlated with structural compaction. Furthermore, in vivo efficacy of DMPD toward amyloid pathology and cognitive impairment was evaluated employing 5xFAD mice of Alzheimer’s disease (AD). Such a small molecule (DMPD) is indicated to noticeably reduce the overall cerebral amyloid load of soluble Aβ forms and amyloid deposits as well as significantly improve cognitive defects in the AD mouse model. Overall, our in vitro and in vivo studies of DMPD toward Aβ with the first molecular-level mechanistic investigations present the feasibility of developing new, innovative approaches that employ redox-active compounds without the structural complexity as next-generation chemical tools for amyloid management.

Neuroprotective, Anti-Amyloidogenic and Neurotrophic Effects of Apigenin in an Alzheimer’s Disease Mouse Model

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Lu Zhang

2013-08-01

Full Text Available Alzheimer’s disease (AD is a neurodegenerative disorder characterized by extracellular senile plaques and intracellular neurofibrillary tangles in the brain. Amyloid-β peptides (Aβ are considered to play a critical role in the onset and progression of AD. Apigenin (4',5,7-trihydroxyflavone is a pharmacologically active agent. Even though some evidence suggests that it has potential neuroprotective effects, no preexisting study has reported any therapeutic effects of apigenin in AD models. In the present study, we examined the effects of apigenin on cognitive function in APP/PS1 double transgenic AD mice and explored its mechanism(s of action. Three-month oral treatment with apigenin rescued learning deficits and relieved memory retention in APP/PS1 mice. Apigenin also showed effects affecting APP processing and preventing Aβ burden due to the down-regulation of BACE1 and β-CTF levels, the relief of Aβ deposition, and the decrease of insoluble Aβ levels. Moreover, apigenin exhibited superoxide anion scavenging effects and improved antioxidative enzyme activity of superoxide dismutase and glutathione peroxidase. In addition, apigenin restored neurotrophic ERK/CREB/BDNF pathway in the cerebral cortex. In conclusion, apigenin may ameliorate AD-associated learning and memory impairment through relieving Aβ burden, suppressing amyloidogenic process, inhibiting oxidative stress, and restoring ERK/CREB/BDNF pathway. Therefore, apigenin appears to represent an alternative medication for the prevention and/or therapy of AD.

Anti-inflammatory and anti-amyloidogenic effects of a small molecule, 2,4-bis(p-hydroxyphenyl-2-butenal in Tg2576 Alzheimer’s disease mice model

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Jin Peng

2013-01-01

Full Text Available Abstract Background Alzheimer’s disease (AD is pathologically characterized by excessive accumulation of amyloid-beta (Aβ fibrils within the brain and activation of astrocytes and microglial cells. In this study, we examined anti-inflammatory and anti-amyloidogenic effects of 2,4-bis(p-hydroxyphenyl-2-butenal (HPB242, an anti-inflammatory compound produced by the tyrosine-fructose Maillard reaction. Methods 12-month-old Tg2576 mice were treated with HPB242 (5 mg/kg for 1 month and then cognitive function was assessed by the Morris water maze test and passive avoidance test. In addition, western blot analysis, Gel electromobility shift assay, immunostaining, immunofluorescence staining, ELISA and enzyme activity assays were used to examine the degree of Aβ deposition in the brains of Tg2576 mice. The Morris water maze task was analyzed using two-way ANOVA with repeated measures. Otherwise were analyzed by one-way ANOVA followed by Dunnett’s post hoc test. Results Treatment of HPB242 (5 mg/kg for 1 month significantly attenuated cognitive impairments in Tg2576 transgenic mice. HPB242 also prevented amyloidogenesis in Tg2576 transgenic mice brains. This can be evidenced by Aβ accumulation, BACE1, APP and C99 expression and β-secretase activity. In addition, HPB242 suppresses the expression of inducible nitric oxide synthase (iNOS and cyclooxygenase-2 (COX-2 as well as activation of astrocytes and microglial cells. Furthermore, activation of nuclear factor-kappaB (NF-κB and signal transducer and activator of transcription 1/3 (STAT1/3 in the brain was potently inhibited by HPB242. Conclusions Thus, these results suggest that HPB242 might be useful to intervene in development or progression of neurodegeneration in AD through its anti-inflammatory and anti-amyloidogenic effects.

Dataset of the molecular dynamics simulations of bilayers consisting of short amyloidogenic peptide VDSWNVLVAG from Bgl2p–glucantransferase of S. cerevisiae cell wall

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Anna V. Glyakina

2016-12-01

Full Text Available The amyloidogenic peptide VDSWNVLVAG from Bgl2p–glucantransferase of Saccharomyces cerevisiae cell wall and its modifying analog VESWNVLVAG were taken for the construction of four types of bilayers which differ by orientation of the peptides in the layers and of the layers relative to each other. These bilayers were used as starting models for the molecular dynamics (MD at three charge states (neutral, pH3, and pH5. The changes of the fraction of secondary structure during 1 ns simulations were received for 96 MD trajectories. The data article contains the necessary information for the construction of models of β-strands organization in the oligomer structure. These results were used in the associated research article “Structural model of amyloid fibrils for amyloidogenic peptide from Bgl2p–glucantransferase of S. cerevisiae cell wall and its modifying analog. New morphology of amyloid fibrils” (Selivanova et al., 2016 [1].

Molecular Origin of Gerstmann-Str ussler-Scheinker Syndrome: Insight from Computer Simulation of an Amyloidogenic Prion Peptide

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Diadone, Isabella [University of L' Aquila, L' Aquila, Italy; DiNola, Alfredo [University of Rome; Smith, Jeremy C [ORNL

2011-01-01

Prion proteins become pathogenic through misfolding. Here, we characterize the folding of a peptide consisting of residues 109 122 of the Syrian hamster prion protein (the H1 peptide) and of a more amyloidogenic A117V point mutant that leads in humans to an inheritable form of the Gerstmann-Straeussler-Scheinker syndrome. Atomistic molecular dynamics simulations are performed for 2.5 s. Both peptides lose their -helical starting conformations and assume a -hairpin that is structurally similar in both systems. In each simulation several unfolding/refolding events occur, leading to convergence of the thermodynamics of the conformational states to within 1 kJ/mol. The similar stability of the -hairpin relative to the unfolded state is observed in the two peptides. However, substantial differences are found between the two unfolded states. A local minimum is found within the free energy unfolded basin of the A117V mutant populated by misfolded collapsed conformations of comparable stability to the -hairpin state, consistent with increased amyloidogenicity. This population, in which V117 stabilizes a hydrophobic core, is absent in the wild-type peptide. These results are supported by simulations of oligomers showing a slightly higher stability of the associated structures and a lower barrier to association for the mutated peptide. Hence, a single point mutation carrying only two additional methyl groups is here shown to be responsible for rather dramatic differences of structuring within the unfolded (misfolded) state.

Cellular processing of the amyloidogenic cystatin C variant of hereditary cerebral hemorrhage with amyloidosis, Icelandic type

DEFF Research Database (Denmark)

Benedikz, Eirikur; Merz, G S; Schwenk, V

1999-01-01

of an amyloidogenic mutation on the intracellular processing of its protein product. The protein, a mutant of the cysteine protease inhibitor cystatin C, is the amyloid precursor protein in Hereditary Cerebral Hemorrhage with Amyloidosis--Icelandic type (HCHWA-I). The amyloid fibers are composed of mutant cystatin C...... (L68Q) that lacks the first 10 amino acids. We have previously shown that processing of wild-type cystatin C entails formation of a transient intracellular dimer that dissociates prior to secretion, such that extracellular cystatin C is monomeric. We report here that the cystatin C mutation engenders...

Comparative two-dimensional gel analysis and microsequencing identifies gelsolin as one of the most prominent downregulated markers of transformed human fibroblast and epithelial cells

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Vandekerckhove, J; Bauw, G; Vancompernolle, K

1990-01-01

A systematic comparison of the protein synthesis patterns of cultured normal and transformed human fibroblasts and epithelial cells, using two-dimensional gel protein analysis combined with computerized imaging and data acquisition, identified a 90-kD protein (SSP 5714) as one of the most striking...... downregulated markers typical of the transformed state. Using the information stored in the comprehensive human cellular protein database, we found this protein strongly expressed in several fetal tissues and one of them, epidermis, served as a source for preparative two-dimensional gel electrophoresis. Partial...... and by coelectrophoresis with purified human gelsolin. These results suggest that an important regulatory protein of the microfilament system may play a role in defining the phenotype of transformed human fibroblast and epithelial cells in culture. Udgivelsesdato: 1990-Jul...

Comparative two-dimensional gel analysis and microsequencing identifies gelsolin as one of the most prominent downregulated markers of transformed human fibroblast and epithelial cells

DEFF Research Database (Denmark)

Vandekerckhove, J; Bauw, G; Vancompernolle, K

1990-01-01

downregulated markers typical of the transformed state. Using the information stored in the comprehensive human cellular protein database, we found this protein strongly expressed in several fetal tissues and one of them, epidermis, served as a source for preparative two-dimensional gel electrophoresis. Partial......A systematic comparison of the protein synthesis patterns of cultured normal and transformed human fibroblasts and epithelial cells, using two-dimensional gel protein analysis combined with computerized imaging and data acquisition, identified a 90-kD protein (SSP 5714) as one of the most striking...... and by coelectrophoresis with purified human gelsolin. These results suggest that an important regulatory protein of the microfilament system may play a role in defining the phenotype of transformed human fibroblast and epithelial cells in culture. Udgivelsesdato: 1990-Jul...

Reduced amyloidogenic processing of the amyloid beta-protein precursor by the small-molecule Differentiation Inducing Factor-1.

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Myre, Michael A; Washicosky, Kevin; Moir, Robert D; Tesco, Giuseppina; Tanzi, Rudolph E; Wasco, Wilma

2009-04-01

The detection of cell cycle proteins in Alzheimer's disease (AD) brains may represent an early event leading to neurodegeneration. To identify cell cycle modifiers with anti-Abeta properties, we assessed the effect of Differentiation-Inducing Factor-1 (DIF-1), a unique, small-molecule from Dictyostelium discoideum, on the proteolysis of the amyloid beta-protein precursor (APP) in a variety of different cell types. We show that DIF-1 slows cell cycle progression through G0/G1 that correlates with a reduction in cyclin D1 protein levels. Western blot analysis of DIF-treated cells and conditioned medium revealed decreases in the levels of secreted APP, mature APP, and C-terminal fragments. Assessment of conditioned media by sandwich ELISA showed reduced levels of Abeta40 and Abeta42, also demonstrating that treatment with DIF-1 effectively decreases the ratio of Abeta42 to Abeta40. In addition, DIF-1 significantly diminished APP phosphorylation at residue T668. Interestingly, site-directed mutagenesis of APP residue Thr668 to alanine or glutamic acid abolished the effect of DIF-1 on APP proteolysis and restored secreted levels of Abeta. Finally, DIF-1 prevented the accumulation of APP C-terminal fragments induced by the proteasome inhibitor lactacystin, and calpain inhibitor N-acetyl-leucyl-leucyl-norleucinal (ALLN). Our findings suggest that DIF-1 affects G0/G1-associated amyloidogenic processing of APP by a gamma-secretase-, proteasome- and calpain-insensitive pathway, and that this effect requires the presence of residue Thr668.

Reduced amyloidogenic processing of the amyloid β-protein precursor by the small-molecule Differentiation Inducing Factor-1

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Myre, Michael A.; Washicosky, Kevin; Moir, Robert D.; Tesco, Giuseppina; Tanzi, Rudolph E.; Wasco, Wilma

2013-01-01

The detection of cell cycle proteins in Alzheimer’s disease (AD) brains may represent an early event leading to neurodegeneration. To identify cell cycle modifiers with anti-Aβ properties, we assessed the effect of Differentiation-Inducing Factor-1 (DIF-1), a unique, small-molecule from Dictyostelium discoideum, on the proteolysis of the amyloid β-protein precursor (APP) in a variety of different cell types. We show that DIF-1 slows cell cycle progression through G0/G1 that correlates with a reduction in cyclin D1 protein levels. Western blot analysis of DIF-treated cells and conditioned medium revealed decreases in the levels of secreted APP, mature APP, and C-terminal fragments. Assessment of conditioned media by sandwich ELISA showed reduced levels of Aβ40 and Aβ42, also demonstrating that treatment with DIF-1 effectively decreases the ratio of Aβ42 to Aβ40. In addition, DIF-1 significantly diminished APP phosphorylation at residue T668. Interestingly, site-directed mutagenesis of APP residue Thr668 to alanine or glutamic acid abolished the effect of DIF-1 on APP proteolysis and restored secreted levels of Aβ. Finally, DIF-1 prevented the accumulation of APP C-terminal fragments induced by the proteasome inhibitor lactacystin, and calpain inhibitor N-acetyl-leucyl-leucyl-norleucinal (ALLN). Our findings suggest that DIF-1 affects G0/G1-associated amyloidogenic processing of APP by a γ-secretase-, proteasome- and calpain-insensitive pathway, and that this effect requires the presence of residue Thr668. PMID:19154786

Amyloid-β Peptide Induces Prion Protein Amyloid Formation: Evidence for Its Widespread Amyloidogenic Effect.

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Honda, Ryo

2018-04-12

Transmissible spongiform encephalopathy is associated with misfolding of prion protein (PrP) into an amyloid β-rich aggregate. Previous studies have indicated that PrP interacts with Alzheimer's disease amyloid-β peptide (Aβ), but it remains elusive how this interaction impacts on the misfolding of PrP. This study presents the first in vitro evidence that Aβ induces PrP-amyloid formation at submicromolar concentrations. Interestingly, systematic mutagenesis of PrP revealed that Aβ requires no specific amino acid sequences in PrP, and induces the misfolding of other unrelated proteins (insulin and lysozyme) into amyloid fibrils in a manner analogous to PrP. This unanticipated nonspecific amyloidogenic effect of Aβ indicates that this peptide might be involved in widespread protein aggregation, regardless of the amino acid sequences of target proteins, and exacerbate the pathology of many neurodegenerative diseases. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

An Amyloidogenic Sequence at the N-Terminus of the Androgen Receptor Impacts Polyglutamine Aggregation

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Emmanuel Oppong

2017-06-01

Full Text Available The human androgen receptor (AR is a ligand inducible transcription factor that harbors an amino terminal domain (AR-NTD with a ligand-independent activation function. AR-NTD is intrinsically disordered and displays aggregation properties conferred by the presence of a poly-glutamine (polyQ sequence. The length of the polyQ sequence as well as its adjacent sequence motifs modulate this aggregation property. AR-NTD also contains a conserved KELCKAVSVSM sequence motif that displays an intrinsic property to form amyloid fibrils under mild oxidative conditions. As peptide sequences with intrinsic oligomerization properties are reported to have an impact on the aggregation of polyQ tracts, we determined the effect of the KELCKAVSVSM on the polyQ stretch in the context of the AR-NTD using atomic force microscopy (AFM. Here, we present evidence for a crosstalk between the amyloidogenic properties of the KELCKAVSVSM motif and the polyQ stretch at the AR-NTD.

A de novo designed 11 kDa polypeptide: model for amyloidogenic intrinsically disordered proteins.

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Topilina, Natalya I; Ermolenkov, Vladimir V; Sikirzhytski, Vitali; Higashiya, Seiichiro; Lednev, Igor K; Welch, John T

2010-07-01

A de novo polypeptide GH(6)[(GA)(3)GY(GA)(3)GE](8)GAH(6) (YE8) has a significant number of identical weakly interacting beta-strands with the turns and termini functionalized by charged amino acids to control polypeptide folding and aggregation. YE8 exists in a soluble, disordered form at neutral pH but is responsive to changes in pH and ionic strength. The evolution of YE8 secondary structure has been successfully quantified during all stages of polypeptide fibrillation by deep UV resonance Raman (DUVRR) spectroscopy combined with other morphological, structural, spectral, and tinctorial characterization. The YE8 folding kinetics at pH 3.5 are strongly dependent on polypeptide concentration with a lag phase that can be eliminated by seeding with a solution of folded fibrillar YE8. The lag phase of polypeptide folding is concentration dependent leading to the conclusion that beta-sheet folding of the 11-kDa amyloidogenic polypeptide is completely aggregation driven.

L-plastin nanobodies perturb matrix degradation, podosome formation, stability and lifetime in THP-1 macrophages.

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Sarah De Clercq

Full Text Available Podosomes are cellular structures acting as degradation 'hot-spots' in monocytic cells. They appear as dot-like structures at the ventral cell surface, enriched in F-actin and actin regulators, including gelsolin and L-plastin. Gelsolin is an ubiquitous severing and capping protein, whereas L-plastin is a leukocyte-specific actin bundling protein. The presence of the capping protein CapG in podosomes has not yet been investigated. We used an innovative approach to investigate the role of these proteins in macrophage podosomes by means of nanobodies or Camelid single domain antibodies. Nanobodies directed against distinct domains of gelsolin, L-plastin or CapG were stably expressed in macrophage-like THP-1 cells. CapG was not enriched in podosomes. Gelsolin nanobodies had no effect on podosome formation or function but proved very effective in tracing distinct gelsolin populations. One gelsolin nanobody specifically targets actin-bound gelsolin and was effectively enriched in podosomes. A gelsolin nanobody that blocks gelsolin-G-actin interaction was not enriched in podosomes demonstrating that the calcium-activated and actin-bound conformation of gelsolin is a constituent of podosomes. THP-1 cells expressing inhibitory L-plastin nanobodies were hampered in their ability to form stable podosomes. Nanobodies did not perturb Ser5 phosphorylation of L-plastin although phosphorylated L-plastin was highly enriched in podosomes. Furthermore, nanobody-induced inhibition of L-plastin function gave rise to an irregular and unstable actin turnover of podosomes, resulting in diminished degradation of the underlying matrix. Altogether these results indicate that L-plastin is indispensable for podosome formation and function in macrophages.

Differential recruitment efficacy of patient-derived amyloidogenic and myeloma light chain proteins by synthetic fibrils-A metric for predicting amyloid propensity.

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Emily B Martin

Full Text Available Monoclonal free light chain (LC proteins are present in the circulation of patients with immunoproliferative disorders such as light chain (AL amyloidosis and multiple myeloma (MM. Light chain-associated amyloid is a complex pathology composed of proteinaceous fibrils and extracellular matrix proteins found in all patients with AL and in ~10-30% of patients who presented with MM. Amyloid deposits systemically in multiple organs and tissues leading to dysfunction and ultimately death. The overall survival of patients with amyloidosis is worse than for those with early stage MM.We have developed a sensitive binding assay quantifying the recruitment of full length, patient-derived LC proteins by synthetic amyloid fibrils, as a method for studying their amyloidogenic potential. In a survey of eight urinary LC, both AL and MM-associated proteins were recruited by synthetic amyloid fibrils; however, AL-associated LC bound significantly more efficiently (p < 0.05 than did MM LCs. The LC proteins used in this study were isolated from urine and presumed to represent a surrogate of serum free light chains.The binding of LC to synthetic fibrils in this assay accurately differentiated LC with amyloidogenic propensity from MM LC that were not associated with clinical amyloid disease. Notably, the LC from a MM patient who subsequently developed amyloid behaved as an AL-associated protein in the assay, indicating the possibility for identifying MM patients at risk for developing amyloidosis based on the light chain recruitment efficacy. With this information, at risk patients can be monitored more closely for the development of amyloidosis, allowing timely administration of novel, amyloid-directed immunotherapies-this approach may improve the prognosis for these patients.

Generic amyloidogenicity of mammalian prion proteins from species susceptible and resistant to prions.

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Nyström, Sofie; Hammarström, Per

2015-05-11

Prion diseases are lethal, infectious diseases associated with prion protein (PrP) misfolding. A large number of mammals are susceptible to both sporadic and acquired prion diseases. Although PrP is highly conserved and ubiquitously expressed in all mammals, not all species exhibit prion disease. By employing full length recombinant PrP from five known prion susceptible species (human, cattle, cat, mouse and hamster) and two species considered to be prion resistant (pig and dog) the amyloidogenicity of these PrPs has been delineated. All the mammalian PrPs, even from resistant species, were swiftly converted from the native state to amyloid-like structure when subjected to a native condition conversion assay. The PrPs displayed amyloidotypic tinctorial and ultrastructural hallmarks. Self-seeded conversion of the PrPs displayed significantly decreased lag phases demonstrating that nucleation dependent polymerization is a dominating mechanism in the fibrillation process. Fibrils from Aβ1-40, Aβ1-42, Lysozyme, Insulin and Transthyretin did not accelerate conversion of HuPrP whereas fibrils from HuPrP90-231 and HuPrP121-231 as well as full length PrPs of all PrPs efficiently seeded conversion showing specificity of the assay requiring the C-terminal PrP sequence. Our findings have implications for PrP misfolding and could have ramifications in the context of prion resistant species and silent carriers.

Neuromodulatory Effect of Thymoquinone in Attenuating Glutamate-Mediated Neurotoxicity Targeting the Amyloidogenic and Apoptotic Pathways

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Ibram Amin Fouad

2018-04-01

Full Text Available Overexposure of the glutamatergic N-methyl-d-aspartate (NMDA receptor to the excitatory neurotransmitter l-glutamic acid leads to neuronal cell death by excitotoxicity as a result of increased intracellular Ca2+, mitochondrial dysfunction, and apoptosis. Moreover, it was previously reported that prolonged activation of the NMDA receptor increased beta-amyloid (Aβ levels in the brain. Thymoquinone (TQ, the active constituent of Nigella sativa seeds, has been shown to have potent antioxidant and antiapoptotic effects. The aim of the present study was to explore the neuromodulatory effects of different doses of TQ (2.5 and 10 mg/kg against apoptotic cell death and Aβ formation resulting from glutamate administration in rats using vitamin E as a positive control. Behavioral changes were assessed using Y-maze and Morris water maze tests for evaluating spatial memory and cognitive functions. Caspase-3, Lactate dehydrogenase, Aβ-42, and cytochrome c gene expression were determined. TQ-treated groups showed significant decreases in the levels of all tested biochemical and behavioral parameters compared with the glutamate-treated group. These findings demonstrated that TQ has a promising neuroprotective activity against glutamate-induced neurotoxicity and this effect is mediated through its anti-amyloidogenic, antioxidant, and antiapoptotic activities.

Persistent depletion of plasma gelsolin (pGSN) after exposure of mice to heavy silicon ions

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Rithidech, Kanokporn Noy; Reungpatthanaphong, Paiboon; Tungjai, Montree; Jangiam, Witawat; Honikel, Louise; Whorton, Elbert B.

2018-05-01

Little is known about plasma proteins that can be used as biomarkers for early and late responses to radiation. The purpose of this study was to determine a link between depletion of plasma gelsolin (pGSN) and cell-death as well as inflammatory responses in the lung (one of the tissues known to be radiosensitive) of the same exposed CBA/CaJ mice after exposure to heavy silicon (28Si) ions. To prevent the development of multiple organ dysfunctions, pGSN (an important component of the extracellular actin-scavenging system) is responsible for the removal of actin that is released into the circulation during inflammation and from dying cells. We evaluated the levels of pGSN in plasma collected from groups of mice (5 mice in each) at 1 week (wk) and 1 month (1 mo) after exposure whole body to different doses of 28Si ions, i.e. 0, 0.1, 0.25, or 0.5 Gy (2 fractionated exposures, 15 days apart that totaled each selected dose). In the same mouse, the measurements of pGSN levels were coupled with the quantitation of injuries in the lung, determined by (a) the levels of cleaved poly (ADP-ribose) polymerase (cleaved-PARP), a marker of apoptotic cell-death, (b) the levels of activated nuclear factor-kappa B (NF-κB) and selected cytokines, i.e. tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and IL-6, from tissue-lysates of the lung. Further, the ratio of neutrophils and lymphocytes (N/L) was determined in the same mouse. Our data indicated: (i) the magnitude of pGSN depletion was dependent to radiation dose at both harvest times, (ii) a persistent depletion of pGSN up to 1 mo post-exposure to 0.25 or 0.5 Gy of 28Si ions, (iii) an inverse-correlation between pGSN depletion and increased levels of cleaved-PARP, including activated NF-κB/pro-inflammatory cytokines in the lung, and (iv) at both harvest times, statistically significant increases in the N/L ratio in groups of mice exposed to 0.5 Gy only. Our findings suggested that depletion in pGSN levels

S100A7, a novel Alzheimer's disease biomarker with non-amyloidogenic alpha-secretase activity acts via selective promotion of ADAM-10.

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Weiping Qin

Full Text Available Alzheimer's disease (AD is the most common cause of dementia among older people. At present, there is no cure for the disease and as of now there are no early diagnostic tests for AD. There is an urgency to develop a novel promising biomarker for early diagnosis of AD. Using surface-enhanced laser desorption ionization-mass spectrometry SELDI-(MS proteomic technology, we identified and purified a novel 11.7-kDa metal- binding protein biomarker whose content is increased in the cerebrospinal fluid (CSF and in the brain of AD dementia subjects as a function of clinical dementia. Following purification and protein-sequence analysis, we identified and classified this biomarker as S100A7, a protein known to be involved in immune responses. Using an adenoviral-S100A7 expression system, we continued to examine the potential role of S100A7 in AD amyloid neuropathology in in vitro model of AD. We found that the expression of exogenous S100A7 in primary cortico-hippocampal neuron cultures derived from Tg2576 transgenic embryos inhibits the generation of beta-amyloid (Abeta(1-42 and Abeta(1-40 peptides, coincidental with a selective promotion of "non- amyloidogenic" alpha-secretase activity via promotion of ADAM (a disintegrin and metalloproteinase-10. Finally, a selective expression of human S100A7 in the brain of transgenic mice results in significant promotion of alpha-secretase activity. Our study for the first time suggests that S100A7 may be a novel biomarker of AD dementia and supports the hypothesis that promotion of S100A7 expression in the brain may selectively promote alpha-secretase activity in the brain of AD precluding the generation of amyloidogenic peptides. If in the future we find that S1000A7 protein content in CSF is sensitive to drug intervention experimentally and eventually in the clinical setting, S100A7 might be developed as novel surrogate index (biomarker of therapeutic efficacy in the characterization of novel drug agents for

Androgen regulation of the androgen receptor coregulators

International Nuclear Information System (INIS)

Urbanucci, Alfonso; Waltering, Kati K; Suikki, Hanna E; Helenius, Merja A; Visakorpi, Tapio

2008-01-01

The critical role of the androgen receptor (AR) in the development of prostate cancer is well recognized. The transcriptional activity of AR is partly regulated by coregulatory proteins. It has been suggested that these coregulators could also be important in the progression of prostate cancer. The aim of this study was to identify coregulators whose expression is regulated by either the androgens and/or by the expression level of AR. We used empty vector and AR cDNA-transfected LNCaP cells (LNCaP-pcDNA3.1, and LNCaP-ARhi, respectively), and grew them for 4 and 24 hours in the presence of dihydrotestosterone (DHT) at various concentrations. The expression of 25 AR coregulators (SRC1, TIF2, PIAS1, PIASx, ARIP4, BRCA1, β-catenin, AIB3, AIB1, CBP, STAT1, NCoR1, AES, cyclin D1, p300, ARA24, LSD1, BAG1L, gelsolin, prohibitin, JMJD2C, JMJD1A, MAK, PAK6 and MAGE11) was then measured by using real-time quantitative RT-PCR (Q-RT-PCR). Five of the coregulators (AIB1, CBP, MAK, BRCA1 and β-catenin) showed more than 2-fold induction and 5 others (cyclin D1, gelsolin, prohibitin, JMJD1A, and JMJD2C) less than 2-fold induction. Overexpression of AR did not affect the expression of the coregulators alone. However, overexpression of AR enhanced the DHT-stimulated expression of MAK, BRCA1, AIB1 and CBP and reduced the level of expression of β-catenin, cyclinD1 and gelsolin. In conclusion, we identified 5 coactivators whose expression was induced by androgens suggesting that they could potentiate AR signaling. Overexpression of AR seems to sensitize cells for low levels of androgens

The chemokine CXCL12 mediates the anti-amyloidogenic action of painless human nerve growth factor.

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Capsoni, Simona; Malerba, Francesca; Carucci, Nicola Maria; Rizzi, Caterina; Criscuolo, Chiara; Origlia, Nicola; Calvello, Mariantonietta; Viegi, Alessandro; Meli, Giovanni; Cattaneo, Antonino

2017-01-01

Nerve growth factor is a therapeutic candidate for Alzheimer's disease. Due to its pain-inducing activity, in current clinical trials nerve growth factor is delivered locally into the brain by neurosurgery, but data on the efficacy of local nerve growth factor delivery in decreasing amyloid-β deposition are not available. To reduce the nerve growth factor pain-inducing side effects, thus avoiding the need for local brain injection, we developed human painless nerve growth factor (hNGFp), inspired by the human genetic disease hereditary sensory and autonomic neuropathy type V. hNGFp has identical neurotrophic potency as wild-type human nerve growth factor, but a 10-fold lower pain sensitizing activity. In this study we first mimicked, in the 5xFAD mouse model, the intraparenchymal delivery of hNGFp used in clinical trials and found it to be ineffective in decreasing amyloid-β plaque load. On the contrary, the same dose of hNGFp delivered intranasally, which was widely biodistributed in the brain and did not induce pain, showed a potent anti-amyloidogenic action and rescued synaptic plasticity and memory deficits. We found that hNGFp acts on glial cells, modulating inflammatory proteins such as the soluble TNFα receptor II and the chemokine CXCL12. We further established that the rescuing effect by hNGFp is mediated by CXCL12, as pharmacological inhibition of CXCL12 receptor CXCR4 occludes most of hNGFp effects. These findings have significant therapeutic implications: (i) we established that a widespread exposure of the brain is required for nerve growth factor to fully exert its neuroprotective actions; and (ii) we have identified a new anti-neurodegenerative pathway as a broad target for new therapeutic opportunities for neurodegenerative diseases. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain.

The signaling cascades of Ganoderma lucidum extracts in stimulating non-amyloidogenic protein secretion in human neuroblastoma SH-SY5Y cell lines.

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Pinweha, Sirinthorn; Wanikiat, Payong; Sanvarinda, Yupin; Supavilai, Porntip

2008-12-19

Ganoderma lucidum (GL) is a medicinal mushroom that possesses various pharmacological properties which are also documented in the ancient reports where GL is praised for its effects on the promotion of health and longevity. In this study, we have investigated the effect of GL mycelia extracts on the non-amyloidogenic protein secretion (sAPPalpha) and the amyloid precursor protein (APP) expression in SH-SY5Y neuroblastoma cells. In order to characterize the signaling pathway which mediates GL-enhanced sAPPalpha secretion, we used inhibitors of nerve growth factor (NGF) signaling pathways, phosphatidylinositol 3 kinase (PI3K), phospholipase Cgamma1 (PLCgamma1), protein kinase C (PKC) and extracellular signal-regulated kinase (ERK1/2), to block GL-mediated sAPPalpha secretion as well as ERK1/2 and PKC activation by using Western blot analysis. Our results provided for the first time evidence that GL mycelia extracts increased APP expression and promoted sAPPalpha secretion. In addition, GL extracts activated ERK1/2 and PKC phosphorylation. The complex signaling cascades of PI3K and ERK may be responsible for GL-mediated sAPPalpha secretion.

Active Achilles tendon kinesitherapy accelerates Achilles tendon repair by promoting neurite regeneration.

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Jielile, Jiasharete; Aibai, Minawa; Sabirhazi, Gulnur; Shawutali, Nuerai; Tangkejie, Wulanbai; Badelhan, Aynaz; Nuerduola, Yeermike; Satewalede, Turde; Buranbai, Darehan; Hunapia, Beicen; Jialihasi, Ayidaer; Bai, Jingping; Kizaibek, Murat

2012-12-15

Active Achilles tendon kinesitherapy facilitates the functional recovery of a ruptured Achilles tendon. However, protein expression during the healing process remains a controversial issue. New Zealand rabbits, aged 14 weeks, underwent tenotomy followed immediately by Achilles tendon microsurgery to repair the Achilles tendon rupture. The tendon was then immobilized or subjected to postoperative early motion treatment (kinesitherapy). Mass spectrography results showed that after 14 days of motion treatment, 18 protein spots were differentially expressed, among which, 12 were up-regulated, consisting of gelsolin isoform b and neurite growth-related protein collapsing response mediator protein 2. Western blot analysis showed that gelsolin isoform b was up-regulated at days 7-21 of motion treatment. These findings suggest that active Achilles tendon kinesitherapy promotes the neurite regeneration of a ruptured Achilles tendon and gelsolin isoform b can be used as a biomarker for Achilles tendon healing after kinesitherapy.

Active Achilles tendon kinesitherapy accelerates Achilles tendon repair by promoting neurite regeneration☆

Science.gov (United States)

Jielile, Jiasharete; Aibai, Minawa; Sabirhazi, Gulnur; Shawutali, Nuerai; Tangkejie, Wulanbai; Badelhan, Aynaz; Nuerduola, Yeermike; Satewalede, Turde; Buranbai, Darehan; Hunapia, Beicen; Jialihasi, Ayidaer; Bai, Jingping; Kizaibek, Murat

2012-01-01

Active Achilles tendon kinesitherapy facilitates the functional recovery of a ruptured Achilles tendon. However, protein expression during the healing process remains a controversial issue. New Zealand rabbits, aged 14 weeks, underwent tenotomy followed immediately by Achilles tendon microsurgery to repair the Achilles tendon rupture. The tendon was then immobilized or subjected to postoperative early motion treatment (kinesitherapy). Mass spectrography results showed that after 14 days of motion treatment, 18 protein spots were differentially expressed, among which, 12 were up-regulated, consisting of gelsolin isoform b and neurite growth-related protein collapsing response mediator protein 2. Western blot analysis showed that gelsolin isoform b was up-regulated at days 7–21 of motion treatment. These findings suggest that active Achilles tendon kinesitherapy promotes the neurite regeneration of a ruptured Achilles tendon and gelsolin isoform b can be used as a biomarker for Achilles tendon healing after kinesitherapy. PMID:25317130

Gold Nanoparticles and Microwave Irradiation Inhibit Beta-Amyloid Amyloidogenesis

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Bastus Neus

2008-01-01

Full Text Available Abstract Peptide-Gold nanoparticles selectively attached to β-amyloid protein (Aβ amyloidogenic aggregates were irradiated with microwave. This treatment produces dramatic effects on the Aβ aggregates, inhibiting both the amyloidogenesis and the restoration of the amyloidogenic potential. This novel approach offers a new strategy to inhibit, locally and remotely, the amyloidogenic process, which could have application in Alzheimer’s disease therapy. We have studied the irradiation effect on the amyloidogenic process in the presence of conjugates peptide-nanoparticle by transmission electronic microscopy observations and by Thioflavine T assays to quantify the amount of fibrils in suspension. The amyloidogenic aggregates rather than the amyloid fibrils seem to be better targets for the treatment of the disease. Our results could contribute to the development of a new therapeutic strategy to inhibit the amyloidogenic process in Alzheimer’s disease.

Proteomic profiling of bone marrow mesenchymal stem cells upon TGF-beta stimulation

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Wang, Daojing; Park, Jennifer S.; Chu, Julia S.F.; Ari, Krakowski; Luo, Kunxin; Chen, David J.; Li, Song

2004-08-08

Bone marrow mesenchymal stem cells (MSCs) can differentiate into different types of cells, and have tremendous potential for cell therapy and tissue engineering. Transforming growth factor {beta}1 (TGF-{beta}) plays an important role in cell differentiation and vascular remodeling. We showed that TGF-{beta} induced cell morphology change and an increase in actin fibers in MSCs. To determine the global effects of TGF-{beta} on MSCs, we employed a proteomic strategy to analyze the effect of TGF-{beta} on the human MSC proteome. By using two-dimensional gel electrophoresis and electrospray ionization coupled to Quadrupole/time-of-flight tandem mass spectrometers, we have generated a proteome reference map of MSCs, and identified {approx}30 proteins with an increase or decrease in expression or phosphorylation in response to TGF-{beta}. The proteins regulated by TGF-{beta} included cytoskeletal proteins, matrix synthesis proteins, membrane proteins, metabolic enzymes, etc. TGF-{beta} increased the expression of smooth muscle (SM) {alpha}-actin and decreased the expression of gelsolin. Over-expression of gelsolin inhibited TGF-{beta}-induced assembly of SM {alpha}-actin; on the other hand, knocking down gelsolin expression enhanced the assembly of {alpha}-actin and actin filaments without significantly affecting {alpha}-actin expression. These results suggest that TGF-{beta} coordinates the increase of {alpha}-actin and the decrease of gelsolin to promote MSC differentiation. This study demonstrates that proteomic tools are valuable in studying stem cell differentiation and elucidating the underlying molecular mechanisms.

Scutellarin Mitigates Aβ-Induced Neurotoxicity and Improves Behavior Impairments in AD Mice

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Yue-Qin Zeng

2018-04-01

Full Text Available Alzheimer’s disease (AD is pathologically characterized by excessive accumulation of amyloid-beta (Aβ within extracellular spaces of the brain. Aggregation of Aβ has been shown to trigger oxidative stress, inflammation, and neurotoxicity resulting in cognitive dysfunction. In this study, we use models of cerebral Aβ amyloidosis to investigate anti-amyloidogenic effects of scutellarin in vitro and in vivo. Our results show that scutellarin, through binding to Aβ42, efficiently inhibits oligomerization as well as fibril formation and reduces Aβ oligomer-induced neuronal toxicity in cell line SH-SY5Y. After nine months of treatment in APP/PS1 double-transgenic mice, scutellarin significantly improves behavior, reduces soluble and insoluble Aβ levels in the brain and plasma, decreases Aβ plaque associated gliosis and levels of proinflammatory cytokines TNF-α and IL-6, attenuates neuroinflammation, displays anti-amyloidogenic effects, and highlights the beneficial effects of intervention on development or progression of AD-like neuropathology.

In vitro aggregation behavior of a non-amyloidogenic λ light chain dimer deriving from U266 multiple myeloma cells.

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Paolo Arosio

Full Text Available Excessive production of monoclonal light chains due to multiple myeloma can induce aggregation-related disorders, such as light chain amyloidosis (AL and light chain deposition diseases (LCDD. In this work, we produce a non-amyloidogenic IgE λ light chain dimer from human mammalian cells U266, which originated from a patient suffering from multiple myeloma, and we investigate the effect of several physicochemical parameters on the in vitro stability of this protein. The dimer is stable in physiological conditions and aggregation is observed only when strong denaturating conditions are applied (acidic pH with salt at large concentration or heating at melting temperature T(m at pH 7.4. The produced aggregates are spherical, amorphous oligomers. Despite the larger β-sheet content of such oligomers with respect to the native state, they do not bind Congo Red or ThT. The impossibility to obtain fibrils from the light chain dimer suggests that the occurrence of amyloidosis in patients requires the presence of the light chain fragment in the monomer form, while dimer can form only amorphous oligomers or amorphous deposits. No aggregation is observed after denaturant addition at pH 7.4 or at pH 2.0 with low salt concentration, indicating that not a generic unfolding but specific conformational changes are necessary to trigger aggregation. A specific anion effect in increasing the aggregation rate at pH 2.0 is observed according to the following order: SO(4(-≫Cl(->H(2PO(4(-, confirming the peculiar role of sulfate in promoting protein aggregation. It is found that, at least for the investigated case, the mechanism of the sulfate effect is related to protein secondary structure changes induced by anion binding.

Sildenafil Decreases BACE1 and Cathepsin B Levels and Reduces APP Amyloidogenic Processing in the SAMP8 Mouse.

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Orejana, Lourdes; Barros-Miñones, Lucía; Jordan, Joaquin; Cedazo-Minguez, Angel; Tordera, Rosa M; Aguirre, Norberto; Puerta, Elena

2015-06-01

The senescence-accelerated mouse-prone 8 (SAMP8), used as a model of aging, displays many established pathological features of Alzheimer's disease. Cognitive impairments and increased levels of hyperphosphorylated tau are found in the hippocampus of SAMP8 mice along with an increased β-secretase activity and amyloid-β (Aβ) depositions that increase in number and extent with age. Based on a previous study from our laboratory showing an amelioration of cognitive impairments and tau pathology by sildenafil, in this study we tested whether this drug could also modulate the amyloid precursor protein amyloidogenic processing in this mouse model. Our results show that the protein levels of the β-secretases β-site amyloid precursor protein cleaving enzyme 1 and cathepsin B are higher in the hippocampus of 9-month-old SAMP8 mice than those of age-matched senescence-resistant-1. Sildenafil (7.5mg/kg for 4 weeks) attenuated learning and memory impairments shown by SAMP8 mice in the passive avoidance test. The increased expression of β-site amyloid precursor protein cleaving enzyme 1 was also reduced by sildenafil, an effect paralleled to decreases in the activities of two β-site amyloid precursor protein cleaving enzyme 1 modulators, calpain and cyclin-dependent kinase 5 protein. Interestingly, sildenafil enhanced both Akt and glycogen synthase kinase-3β (ser9) phosphorylation, which could be mediating the reduction in cathepsin B levels found in the hippocampus of sildenafil-treated SAMP8 mice. Sildenafil-induced reduction in β-site amyloid precursor protein cleaving enzyme 1 and cathepsin B expression in SAMP8 mice was associated with a decrease in hippocampal Aβ42 levels which, in turn, could mediate the parallel decline in glial fibrillary acidic protein expression observed in these animals. These findings highlight the therapeutic potential of sildenafil in Alzheimer's disease pathogenesis. © The Author 2014. Published by Oxford University Press on behalf of

Huperzine A alleviates synaptic deficits and modulates amyloidogenic and nonamyloidogenic pathways in APPswe/PS1dE9 transgenic mice.

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Wang, Ying; Tang, Xi Can; Zhang, Hai Yan

2012-02-01

Huperzine A (HupA) is a potent acetylcholinesterase inhibitor (AChEI) used in the treatment of Alzheimer's disease (AD). Recently, HupA was shown to be active in modulating the nonamyloidogenic metabolism of β-amyloid precursor protein (APP) in APP-transfected human embryonic kidney cell line (HEK293swe). However, in vivo research concerning the mechanism of HupA in APP transgenic mice has not yet been fully elucidated. The present study indicates that the loss of dendritic spine density and synaptotagmin levels in the brain of APPswe/presenilin-1 (PS1) transgenic mice was significantly ameliorated by chronic HupA treatment and provides evidence that this neuroprotection was associated with reduced amyloid plaque burden and oligomeric β-amyloid (Aβ) levels in the cortex and hippocampus of APPswe/PS1dE9 transgenic mice. Our findings further demonstrate that the amelioration effect of HupA on Aβ deposits may be mediated, at least in part, by regulation of the compromised expression of a disintegrin and metalloprotease 10 (ADAM10) and excessive membrane trafficking of β-site APP cleavage enzyme 1 (BACE1) in these transgenic mice. In addition, extracellular signal-regulated kinases 1/2 (Erk1/2) phosphorylation may also be partially involved in the effect of HupA on APP processing. In conclusion, our work for the first time demonstrates the neuroprotective effect of HupA on synaptic deficits in APPswe/PS1dE9 transgenic mice and further clarifies the potential pharmacological targets for this protective effect, in which modulation of nonamyloidogenic and amyloidogenic APP processing pathways may be both involved. These findings may provide adequate evidence for the clinical and experimental benefits gained from HupA treatment. Copyright © 2011 Wiley Periodicals, Inc.

Oxidized epigallocatechin gallate inhibited lysozyme fibrillation more strongly than the native form

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Ting-Ting An

2017-04-01

Full Text Available Epigallocatechin gallate (EGCG, the most abundant flavanoid in green tea, is currently being evaluated in the clinic due to its benefits in the treatment of amyloid disorders. Its anti-amyloidogenic effect has been attributed to direct interaction of the intact molecule with misfolded polypeptides. In addition, antioxidant activity is also involved in the anti-amyloidogenic role. The detailed molecular mechanism is still unclear and requires further investigation. In the present study, the kinetics of EGCG oxidation and the anti-amyloidogenic effect of the resultant oxidation substances have been examined. The results indicate that EGCG degrades in a medium at pH 8.0 with a half-life less than 2 h. By utilizing lysozyme as an in vitro model, the oxidized EGCG demonstrates a more potent anti-amyloidogenic capacity than the intact molecule, as shown by ThT and ANS fluorescence, TEM determination, and hemolytic assay. The oxidized EGCG also has a stronger disruptive effect on preformed fibrils than the native form. Ascorbic acid eliminates the disruptive role of native EGCG on the fibrils, suggesting that oxidation is a prerequisite in fibril disruption. The results of this work demonstrate that oxidized EGCG plays a more important role than the intact molecule in anti-amyloidogenic activity. These insights into the action of EGCG may provide a novel route to understand the anti-amyloidogenic activity of natural polyphenols.

Impact of Cytokines and Chemokines on Alzheimer's Disease Neuropathological Hallmarks.

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Domingues, Catarina; da Cruz E Silva, Odete A B; Henriques, Ana Gabriela

2017-01-01

Alzheimer's disease (AD) is the most common neurodegenerative disorder, neuropathologically characterized by aggregates of β-amyloid peptides, which deposit as senile plaques, and of TAU protein, which forms neurofibrillary tangles. It is now widely accepted that neuroinflammation is implicated in AD pathogenesis. Indeed, inflammatory mediators, such as cytokines and chemokines (chemotactic cytokines) can impact on the Alzheimer´s amyloid precursor protein by affecting its expression levels and amyloidogenic processing and/or β -amyloid aggregation. Additionally, cytokines and chemokines can influence kinases' activities, leading to abnormal TAU phosphorylation. To date there is no cure for AD, but several therapeutic strategies have been directed to prevent neuroinflammation. Anti-inflammatory, but also anti-amyloidogenic compounds, such as flavonoids were shown to favourably modulate some pathological events associated with neurodegeneration. This review focuses on the role of cytokines and chemokines in AD-associated pathologies, and summarizes the potential anti-inflammatory therapeutic approaches aimed at preventing or slowing down disease progression. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Design, Engineering and Application of an Amyloidogenic Protein, SBAFP-m1, for use in Nanotechnological Applications

Science.gov (United States)

Peralta, Maria del Refugio

successful as homogeneous fibrils continued to form. Engineering an intermolecular disulfide bond across the dimer interface was also unsuccessful due to incomplete product and mixed disulfide formation. Heterogeneous fibril assembly via a SpyTag and SpyCatcher moiety resulted in improper folding of the parent, amyloid proteins, although with further optimization, heterogeneous fibril assembly should be attainable. This work illustrates from start to finish the ability to engineer an extremely strong and highly resistant amyloidogenic protein and its ability to be functionalized as a biological scaffold for the synthesis of nanowires. The potential for the engineered protein, SBAFP-m1, to be used in a variety of other nanotechnological applications is promising.

Curcumin and Apigenin - novel and promising therapeutics against chronic neuroinflammation in Alzheimer′s disease

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Madhuri Venigalla

2015-01-01

Full Text Available Alzheimer′s disease is a progressive neurodegenerative disorder, characterized by deposition of amyloid beta, neurofibrillary tangles, astrogliosis and microgliosis, leading to neuronal dysfunction and loss in the brain. Current treatments for Alzheimer′s disease primarily focus on enhancement of cholinergic transmission. However, these treatments are only symptomatic, and no disease-modifying drug is available for Alzheimer′s disease patients. This review will provide an overview of the proven antioxidant, anti-inflammatory, anti-amyloidogenic, neuroprotective, and cognition-enhancing effects of curcumin and apigenin and discuss the potential of these compounds for Alzheimer′s disease prevention and treatment. We suggest that these compounds might delay the onset of Alzheimer′s disease or slow down its progression, and they should enter clinical trials as soon as possible.

Mild oxidative stress induces redistribution of BACE1 in non-apoptotic conditions and promotes the amyloidogenic processing of Alzheimer's disease amyloid precursor protein.

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Jiang-Li Tan

Full Text Available BACE1 is responsible for β-secretase cleavage of the amyloid precursor protein (APP, which represents the first step in the production of amyloid β (Aβ peptides. Previous reports, by us and others, have indicated that the levels of BACE1 protein and activity are increased in the brain cortex of patients with Alzheimer's disease (AD. The association between oxidative stress (OS and AD has prompted investigations that support the potentiation of BACE1 expression and enzymatic activity by OS. Here, we have established conditions to analyse the effects of mild, non-lethal OS on BACE1 in primary neuronal cultures, independently from apoptotic mechanisms that were shown to impair BACE1 turnover. Six-hour treatment of mouse primary cortical cells with 10-40 µM hydrogen peroxide did not significantly compromise cell viability but it did produce mild oxidative stress (mOS, as shown by the increased levels of reactive radical species and activation of p38 stress kinase. The endogenous levels of BACE1 mRNA and protein were not significantly altered in these conditions, whereas a toxic H2O2 concentration (100 µM caused an increase in BACE1 protein levels. Notably, mOS conditions resulted in increased levels of the BACE1 C-terminal cleavage product of APP, β-CTF. Subcellular fractionation techniques showed that mOS caused a major rearrangement of BACE1 localization from light to denser fractions, resulting in an increased distribution of BACE1 in fractions containing APP and markers for trans-Golgi network and early endosomes. Collectively, these data demonstrate that mOS does not modify BACE1 expression but alters BACE1 subcellular compartmentalization to favour the amyloidogenic processing of APP, and thus offer new insight in the early molecular events of AD pathogenesis.

Specific binding of a naturally occurring amyloidogenic fragment of Streptococcus mutans adhesin P1 to intact P1 on the cell surface characterized by solid state NMR spectroscopy

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Tang, Wenxing; Bhatt, Avni [University of Florida, Department of Biochemistry and Molecular Biology, College of Medicine (United States); Smith, Adam N. [University of Florida, Department of Chemistry, College of Liberal Arts and Sciences (United States); Crowley, Paula J.; Brady, L. Jeannine, E-mail: jbrady@dental.ufl.edu [University of Florida, Department of Oral Biology, College of Dentistry (United States); Long, Joanna R., E-mail: jrlong@ufl.edu [University of Florida, Department of Biochemistry and Molecular Biology, College of Medicine (United States)

2016-02-15

The P1 adhesin (aka Antigen I/II or PAc) of the cariogenic bacterium Streptococcus mutans is a cell surface-localized protein involved in sucrose-independent adhesion and colonization of the tooth surface. The immunoreactive and adhesive properties of S. mutans suggest an unusual functional quaternary ultrastructure comprised of intact P1 covalently attached to the cell wall and interacting with non-covalently associated proteolytic fragments thereof, particularly the ∼57-kDa C-terminal fragment C123 previously identified as Antigen II. S. mutans is capable of amyloid formation when grown in a biofilm and P1 is among its amyloidogenic proteins. The C123 fragment of P1 readily forms amyloid fibers in vitro suggesting it may play a role in the formation of functional amyloid during biofilm development. Using wild-type and P1-deficient strains of S. mutans, we demonstrate that solid state NMR (ssNMR) spectroscopy can be used to (1) globally characterize cell walls isolated from a Gram-positive bacterium and (2) characterize the specific binding of heterologously expressed, isotopically-enriched C123 to cell wall-anchored P1. Our results lay the groundwork for future high-resolution characterization of the C123/P1 ultrastructure and subsequent steps in biofilm formation via ssNMR spectroscopy, and they support an emerging model of S. mutans colonization whereby quaternary P1-C123 interactions confer adhesive properties important to binding to immobilized human salivary agglutinin.

Specific binding of a naturally occurring amyloidogenic fragment of Streptococcus mutans adhesin P1 to intact P1 on the cell surface characterized by solid state NMR spectroscopy

International Nuclear Information System (INIS)

Tang, Wenxing; Bhatt, Avni; Smith, Adam N.; Crowley, Paula J.; Brady, L. Jeannine; Long, Joanna R.

2016-01-01

The P1 adhesin (aka Antigen I/II or PAc) of the cariogenic bacterium Streptococcus mutans is a cell surface-localized protein involved in sucrose-independent adhesion and colonization of the tooth surface. The immunoreactive and adhesive properties of S. mutans suggest an unusual functional quaternary ultrastructure comprised of intact P1 covalently attached to the cell wall and interacting with non-covalently associated proteolytic fragments thereof, particularly the ∼57-kDa C-terminal fragment C123 previously identified as Antigen II. S. mutans is capable of amyloid formation when grown in a biofilm and P1 is among its amyloidogenic proteins. The C123 fragment of P1 readily forms amyloid fibers in vitro suggesting it may play a role in the formation of functional amyloid during biofilm development. Using wild-type and P1-deficient strains of S. mutans, we demonstrate that solid state NMR (ssNMR) spectroscopy can be used to (1) globally characterize cell walls isolated from a Gram-positive bacterium and (2) characterize the specific binding of heterologously expressed, isotopically-enriched C123 to cell wall-anchored P1. Our results lay the groundwork for future high-resolution characterization of the C123/P1 ultrastructure and subsequent steps in biofilm formation via ssNMR spectroscopy, and they support an emerging model of S. mutans colonization whereby quaternary P1-C123 interactions confer adhesive properties important to binding to immobilized human salivary agglutinin

Specific binding of a naturally occurring amyloidogenic fragment of Streptococcus mutans adhesin P1 to intact P1 on the cell surface characterized by solid state NMR spectroscopy.

Science.gov (United States)

Tang, Wenxing; Bhatt, Avni; Smith, Adam N; Crowley, Paula J; Brady, L Jeannine; Long, Joanna R

2016-02-01

The P1 adhesin (aka Antigen I/II or PAc) of the cariogenic bacterium Streptococcus mutans is a cell surface-localized protein involved in sucrose-independent adhesion and colonization of the tooth surface. The immunoreactive and adhesive properties of S. mutans suggest an unusual functional quaternary ultrastructure comprised of intact P1 covalently attached to the cell wall and interacting with non-covalently associated proteolytic fragments thereof, particularly the ~57-kDa C-terminal fragment C123 previously identified as Antigen II. S. mutans is capable of amyloid formation when grown in a biofilm and P1 is among its amyloidogenic proteins. The C123 fragment of P1 readily forms amyloid fibers in vitro suggesting it may play a role in the formation of functional amyloid during biofilm development. Using wild-type and P1-deficient strains of S. mutans, we demonstrate that solid state NMR (ssNMR) spectroscopy can be used to (1) globally characterize cell walls isolated from a Gram-positive bacterium and (2) characterize the specific binding of heterologously expressed, isotopically-enriched C123 to cell wall-anchored P1. Our results lay the groundwork for future high-resolution characterization of the C123/P1 ultrastructure and subsequent steps in biofilm formation via ssNMR spectroscopy, and they support an emerging model of S. mutans colonization whereby quaternary P1-C123 interactions confer adhesive properties important to binding to immobilized human salivary agglutinin.

Bilateral optic neuropathy in a patient with familial amyloidotic polyneuropathy

DEFF Research Database (Denmark)

Hamann, Steffen; Jensen, Peter Koch; Fledelius, Hans Callø

2013-01-01

Amyloidogenic transthyretin (ATTR)-related familial amyloidotic polyneuropathy (FAP) is an autosomal-dominant hereditary disease characterised by slowly progressive peripheral sensorimotor and autonomic neuropathy and tissue involvement of the heart, kidneys and central nervous system. Secondary...... ATTR Val30Met mutation. After 11 years of ophthalmic follow-up best-corrected visual acuity was 20/100 in his seeing eye, which further had visual field findings suggestive of optic neuropathy. This was also the diagnosis underlying the preceding insidious full loss of vision in the fellow eye......, with colour Doppler imaging to support an ischaemic aetiology. To our knowledge, this is the first report of ischaemic optic neuropathy in this familial amyloid disorder....

The proteome response to amyloid protein expression in vivo.

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Ricardo A Gomes

Full Text Available Protein misfolding disorders such as Alzheimer, Parkinson and transthyretin amyloidosis are characterized by the formation of protein amyloid deposits. Although the nature and location of the aggregated proteins varies between different diseases, they all share similar molecular pathways of protein unfolding, aggregation and amyloid deposition. Most effects of these proteins are likely to occur at the proteome level, a virtually unexplored reality. To investigate the effects of an amyloid protein expression on the cellular proteome, we created a yeast expression system using human transthyretin (TTR as a model amyloidogenic protein. We used Saccharomyces cerevisiae, a living test tube, to express native TTR (non-amyloidogenic and the amyloidogenic TTR variant L55P, the later forming aggregates when expressed in yeast. Differential proteome changes were quantitatively analyzed by 2D-differential in gel electrophoresis (2D-DIGE. We show that the expression of the amyloidogenic TTR-L55P causes a metabolic shift towards energy production, increased superoxide dismutase expression as well as of several molecular chaperones involved in protein refolding. Among these chaperones, members of the HSP70 family and the peptidyl-prolyl-cis-trans isomerase (PPIase were identified. The latter is highly relevant considering that it was previously found to be a TTR interacting partner in the plasma of ATTR patients but not in healthy or asymptomatic subjects. The small ubiquitin-like modifier (SUMO expression is also increased. Our findings suggest that refolding and degradation pathways are activated, causing an increased demand of energetic resources, thus the metabolic shift. Additionally, oxidative stress appears to be a consequence of the amyloidogenic process, posing an enhanced threat to cell survival.

Maximally asymmetric transbilayer distribution of anionic lipids alters the structure and interaction with lipids of an amyloidogenic protein dimer bound to the membrane surface.

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Cheng, Sara Y; Chou, George; Buie, Creighton; Vaughn, Mark W; Compton, Campbell; Cheng, Kwan H

2016-03-01

We used molecular dynamics simulations to explore the effects of asymmetric transbilayer distribution of anionic phosphatidylserine (PS) lipids on the structure of a protein on the membrane surface and subsequent protein-lipid interactions. Our simulation systems consisted of an amyloidogenic, beta-sheet rich dimeric protein (D42) absorbed to the phosphatidylcholine (PC) leaflet, or protein-contact PC leaflet, of two membrane systems: a single-component PC bilayer and double PC/PS bilayers. The latter comprised of a stable but asymmetric transbilayer distribution of PS in the presence of counterions, with a 1-component PC leaflet coupled to a 1-component PS leaflet in each bilayer. The maximally asymmetric PC/PS bilayer had a non-zero transmembrane potential (TMP) difference and higher lipid order packing, whereas the symmetric PC bilayer had a zero TMP difference and lower lipid order packing under physiologically relevant conditions. Analysis of the adsorbed protein structures revealed weaker protein binding, more folding in the N-terminal domain, more aggregation of the N- and C-terminal domains and larger tilt angle of D42 on the PC leaflet surface of the PC/PS bilayer versus the PC bilayer. Also, analysis of protein-induced membrane structural disruption revealed more localized bilayer thinning in the PC/PS versus PC bilayer. Although the electric field profile in the non-protein-contact PS leaflet of the PC/PS bilayer differed significantly from that in the non-protein-contact PC leaflet of the PC bilayer, no significant difference in the electric field profile in the protein-contact PC leaflet of either bilayer was evident. We speculate that lipid packing has a larger effect on the surface adsorbed protein structure than the electric field for a maximally asymmetric PC/PS bilayer. Our results support the mechanism that the higher lipid packing in a lipid leaflet promotes stronger protein-protein but weaker protein-lipid interactions for a dimeric protein on

Maternal serum proteome changes between the first and third trimester of pregnancy in rural southern Nepal.

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Scholl, P F; Cole, R N; Ruczinski, I; Gucek, M; Diez, R; Rennie, A; Nathasingh, C; Schulze, K; Christian, P; Yager, J D; Groopman, J D; West, K P

2012-05-01

Characterization of normal changes in the serum proteome during pregnancy may enhance understanding of maternal physiology and lead to the development of new gestational biomarkers. In 23 Nepalese pregnant women who delivered at term, two-dimensional difference in-gel electrophoresis (DIGE) was used to assess changes in relative protein abundance between paired serum samples collected in the first and third trimesters. One-hundred and forty-five of over 700 protein spots in DIGE gels (pI 4.2-6.8) exhibited nominally significant (p < 0.05) differences in abundance across trimesters. Additional filtering using a Bonferroni correction reduced the number of significant (p < 0.00019) spots to 61. Mass spectrometric analysis detected 38 proteins associated with gestational age, cytoskeletal remodeling, blood pressure regulation, lipid and nutrient transport, and inflammation. One new protein, pregnancy-specific β-glycoprotein 4 was detected. A follow-up isotope tagging for relative and absolute quantitation (iTRAQ) experiment of six mothers from the DIGE study revealed 111 proteins, of which 11 exhibited significant (p < 0.05) differences between trimesters. Four of these proteins: gelsolin, complement C1r subcomponent, α-1-acid glycoprotein, and α-1B-glycoprotein also changed in the DIGE analysis. Although not previously associated with normal pregnancy, gelsolin decreased in abundance by the third trimester (p < 0.01) in DIGE, iTRAQ and Western analyses. Changes in abundance of proteins in serum that are associated with syncytiotrophoblasts (gelsolin, pregnancy-specific β-1 glycoprotein 1 and β-2-glycoprotein I) probably reflect dynamics of a placental proteome shed into maternal circulation during pregnancy. Measurement of changes in the maternal serum proteome, when linked with birth outcomes, may yield biomarkers for tracking reproductive health in resource poor settings in future studies. Published by Elsevier Ltd.

Interaction of human laminin receptor with Sup35, the [PSI⁺] prion-forming protein from S. cerevisiae: a yeast model for studies of LamR interactions with amyloidogenic proteins.

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Christine Pampeno

Full Text Available The laminin receptor (LamR is a cell surface receptor for extracellular matrix laminin, whereas the same protein within the cell interacts with ribosomes, nuclear proteins and cytoskeletal fibers. LamR has been shown to be a receptor for several bacteria and viruses. Furthermore, LamR interacts with both cellular and infectious forms of the prion protein, PrP(C and PrP(Sc. Indeed, LamR is a receptor for PrP(C. Whether LamR interacts with PrP(Sc exclusively in a capacity of the PrP receptor, or LamR specifically recognizes prion determinants of PrP(Sc, is unclear. In order to explore whether LamR has a propensity to interact with prions and amyloids, we examined LamR interaction with the yeast prion-forming protein, Sup35. Sup35 is a translation termination factor with no homology or functional relationship to PrP. Plasmids expressing LamR or LamR fused with the green fluorescent protein (GFP were transformed into yeast strain variants differing by the presence or absence of the prion conformation of Sup35, respectively [PSI⁺] and [psi⁻]. Analyses by immunoprecipitation, centrifugal fractionation and fluorescent microscopy reveal interaction between LamR and Sup35 in [PSI⁺] strains. The presence of [PSI⁺] promotes LamR co-precipitation with Sup35 as well as LamR aggregation. In [PSI⁺] cells, LamR tagged with GFP or mCherry forms bright fluorescent aggregates that co-localize with visible [PSI⁺] foci. The yeast prion model will facilitate studying the interaction of LamR with amyloidogenic prions in a safe and easily manipulated system that may lead to a better understanding and treatment of amyloid diseases.

Pharmacophore-based design and discovery of (-)-meptazinol carbamates as dual modulators of cholinesterase and amyloidogenesis.

Science.gov (United States)

Xie, Qiong; Zheng, Zhaoxi; Shao, Biyun; Fu, Wei; Xia, Zheng; Li, Wei; Sun, Jian; Zheng, Wei; Zhang, Weiwei; Sheng, Wei; Zhang, Qihong; Chen, Hongzhuan; Wang, Hao; Qiu, Zhuibai

2017-12-01

Multifunctional carbamate-type acetylcholinesterase (AChE) inhibitors with anti-amyloidogenic properties like phenserine are potential therapeutic agents for Alzheimer's disease (AD). We reported here the design of new carbamates using pharmacophore model strategy to modulate both cholinesterase and amyloidogenesis. A five-feature pharmacophore model was generated based on 25 carbamate-type training set compounds. (-)-Meptazinol carbamates that superimposed well upon the model were designed and synthesized, which exhibited nanomolar AChE inhibitory potency and good anti-amyloidogenic properties in in vitro test. The phenylcarbamate 43 was highly potent (IC 50 31.6 nM) and slightly selective for AChE, and showed low acute toxicity. In enzyme kinetics assay, 43 exhibited uncompetitive inhibition and reacted by pseudo-irreversible mechanism. 43 also showed amyloid-β (Aβ) lowering effects (51.9% decrease of Aβ 42 ) superior to phenserine (31% decrease of total Aβ) in SH-SY5Y-APP 695 cells at 50 µM. The dual actions of 43 on cholinergic and amyloidogenic pathways indicated potential uses as symptomatic and disease-modifying agents.

The progressive tax

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Estrada, Fernando

2010-01-01

This article describes the argumentative structure of Hayek on the relationship between power to tax and the progressive tax. It is observed throughout its work giving special attention to two works: The Constitution of Liberty (1959) and Law, Legislation and Liberty, vol3; The Political Order of Free People, 1979) Hayek describes one of the arguments most complete information bout SFP progressive tax systems (progressive tax). According to the author the history of the tax progressive system...

When Progressive Disease Does Not Mean Treatment Failure: Reconsidering the Criteria for Progression

Science.gov (United States)

2012-01-01

Although progression-based endpoints, such as progression-free survival, are often key clinical trial endpoints for anticancer agents, the clinical meaning of “objective progression” is much less certain. As scrutiny of progression-based endpoints in clinical trials increases, it should be remembered that the Response Evaluation Criteria In Solid Tumors (RECIST) progression criteria were not developed as a surrogate for survival. Now that progression-free survival has come to be an increasingly important trial endpoint, the criteria that define progression deserve critical evaluation to determine whether alternate definitions of progression might facilitate the development of stronger surrogate endpoints and more meaningful trial results. In this commentary, we review the genesis of the criteria for progression, highlight recent data that question their value as a marker of treatment failure, and advocate for several research strategies that could lay the groundwork for a clinically validated definition of disease progression in solid tumor oncology. PMID:22927506

Assessment value of transcranial Doppler hemodynamic typing for prognosis of patients with acute middle cerebral artery infarction

Directory of Open Access Journals (Sweden)

Jing Xie

2016-08-01

Full Text Available Objective: To analyze the assessment value of transcranial Doppler hemodynamic typing for prognosis of patients with acute middle cerebral artery infarction. Methods: A total of 54 cases of patients with acute middle cerebral artery infarction who received treatment in our hospital from January 2014 to June 2015 were included for study, and according to different types, they were divided into total occlusion group 17 cases, partial occlusion group 28 cases and nonocclusion group 9 cases. Differences in levels of infarction-related proteins, coagulation-related indicators, illness-related factors, etc in circulating blood of three groups were compared, and the correlation of middle cerebral arterial systolic velocity (Vs and diastolic velocity (Vd with above indicators was further analyzed. Results: Vs and Vd values of non-occlusion group were higher than those of total occlusion group and partial occlusion group, and Vs and Vd values of partial occlusion group were higher than those of total occlusion group; serum Gelsolin, PT, APTT and TT values of non-occlusion group were higher, SAA, Apo- CⅡ, HbA1c, GSP, A毬, HSP70, FIB, D-D, Copeptin, P-selectin, PTX3, TPO and FFA values were lower, and compared with partial occlusion group and total occlusion group, differences were significant; Gelsolin, PT, APTT and TT values of partial occlusion group were higher than those of total occlusion group, and SAA, Apo- CⅡ, HbA1c, GSP, A毬, HSP70, FIB, D-D, Copeptin, P-selectin, PTX3, TPO and FFA values were lower than those of total occlusion group; middle cerebral arterial Vs and Vd values were directly proportional to Gelsolin, PT, APTT and TT values, and inversely proportional to SAA, Apo- CⅡ, HbA1c, GSP, A毬, HSP70, FIB, D-D, Copeptin, P-selectin, PTX3, TPO and FFA values. Conclusions: Transcranial Doppler hemodynamic typing can be the reliable way to judge the severity of acute middle cerebral artery infarction, and has great value in assessing

Progress Report

DEFF Research Database (Denmark)

Duer, Karsten

1999-01-01

Progress report describing the work carried out by the Danish participant in the ALTSET project in the period January 1999 to July 1999.......Progress report describing the work carried out by the Danish participant in the ALTSET project in the period January 1999 to July 1999....

Progress Report

Science.gov (United States)

2018-05-16

This report summarizes the annual progress of EPA’s Clean Air Markets Programs such as the Acid Rain Program (ARP) and the Cross-State Air Pollution Rule (CSAPR). EPA systematically collects data on emissions, compliance, and environmental effects, these data are highlighted in our Progress Reports.

[Progressive visual agnosia].

Science.gov (United States)

Sugimoto, Azusa; Futamura, Akinori; Kawamura, Mitsuru

2011-10-01

Progressive visual agnosia was discovered in the 20th century following the discovery of classical non-progressive visual agnosia. In contrast to the classical type, which is caused by cerebral vascular disease or traumatic injury, progressive visual agnosia is a symptom of neurological degeneration. The condition of progressive visual loss, including visual agnosia, and posterior cerebral atrophy was named posterior cortical atrophy (PCA) by Benson et al. (1988). Progressive visual agnosia is also observed in semantic dementia (SD) and other degenerative diseases, but there is a difference in the subtype of visual agnosia associated with these diseases. Lissauer (1890) classified visual agnosia into apperceptive and associative types, and it in most cases, PCA is associated with the apperceptive type. However, SD patients exhibit symptoms of associative visual agnosia before changing to those of semantic memory disorder. Insights into progressive visual agnosia have helped us understand the visual system and discover how we "perceive" the outer world neuronally, with regard to consciousness. Although PCA is a type of atypical dementia, its diagnosis is important to enable patients to live better lives with appropriate functional support.

Bone marrow amyloid spherulites in a case of AL amyloidosis.

Science.gov (United States)

Bommannan B K, Karthik; Sonai, Mukinkumar; Sachdeva, Man Updesh Singh

2016-05-01

Parallel arrangement of β-pleated sheets by amyloidogenic proteins is a well known phenomenon. Rarely, amyloid fibrils undergo radial orientation to form globular structures called spherulites. These amyloid spherulites show Maltese cross pattern under polarized microscopy. The clinical significance of amyloid spherulites is undetermined. Amyloidogenic proteins like insulin and β-lactoglobulin form spherulites in vitro. The senile plaques of Alzheimer's disease rarely form in vivo spherulites. Amyloid spherulites have been described in the liver and small intestine. For the first time, we document amyloid spherulite formation in the bone marrow biopsy of an AL amyloidosis patient. Copyright © 2016 Elsevier Inc. All rights reserved.

Psychological functioning in primary progressive versus secondary progressive multiple sclerosis

DEFF Research Database (Denmark)

Vleugels, L; Pfennings, L E; Pouwer, F

1998-01-01

Psychological functioning in two types of multiple sclerosis (MS) patients is assessed: primary progressive (PP) and secondary progressive (SP) patients. On the basis of differences in clinical course and underlying pathology we hypothesized that primary progressive patients and secondary...... progressive patients might have different psychological functioning. Seventy patients treated in an MS centre were examined cross-sectionally. Forty had an SP course of MS and 30 a PP course. The 33 male and 37 female patients had a mean age of 48.4 years (SD 11.2) and mean age of onset of MS of 30.7 years...... (SD 11.1). Patients completed questionnaires measuring among others the following aspects of psychological functioning: depression (BDI, SCL-90), anxiety (STAI, SCL-90), agoraphobia (SCL-90), somatic complaints (SCL-90), hostility (SCL-90) and attitude towards handicap (GHAS). Patients with a PP...

Primary Progressive Aphasia

Science.gov (United States)

... which cause different symptoms. Semantic variant primary progressive aphasia Symptoms include these difficulties: Comprehending spoken or written ... word meanings Naming objects Logopenic variant primary progressive aphasia Symptoms include: Having difficulty retrieving words Frequently pausing ...

Progressive Business

DEFF Research Database (Denmark)

Christiansen, Christian O.

2016-01-01

Guest Post to the Society for U.S. Intellectual History Blog. Brief introduction to the book Progressive Business: An Intellectual History of the Role of Business in American Society, Oxford U.P., 2015.......Guest Post to the Society for U.S. Intellectual History Blog. Brief introduction to the book Progressive Business: An Intellectual History of the Role of Business in American Society, Oxford U.P., 2015....

White matter lesion progression

DEFF Research Database (Denmark)

Hofer, Edith; Cavalieri, Margherita; Bis, Joshua C

2015-01-01

10 cohorts. To assess the relative contribution of genetic factors to progression of WML, we compared in 7 cohorts risk models including demographics, vascular risk factors plus single-nucleotide polymorphisms that have been shown to be associated cross-sectionally with WML in the current......BACKGROUND AND PURPOSE: White matter lesion (WML) progression on magnetic resonance imaging is related to cognitive decline and stroke, but its determinants besides baseline WML burden are largely unknown. Here, we estimated heritability of WML progression, and sought common genetic variants...... associated with WML progression in elderly participants from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium. METHODS: Heritability of WML progression was calculated in the Framingham Heart Study. The genome-wide association study included 7773 elderly participants from...

Quantitative proteomic analysis of serum from pregnant women carrying a fetus with conotruncal heart defect using isobaric tags for relative and absolute quantitation (iTRAQ labeling.

Directory of Open Access Journals (Sweden)

Ying Zhang

Full Text Available To identify differentially expressed proteins from serum of pregnant women carrying a conotruncal heart defects (CTD fetus, using proteomic analysis.The study was conducted using a nested case-control design. The 5473 maternal serum samples were collected at 14-18 weeks of gestation. The serum from 9 pregnant women carrying a CTD fetus, 10 with another CHD (ACHD fetus, and 11 with a normal fetus were selected from the above samples, and analyzed by using isobaric tags for relative and absolute quantitation (iTRAQ coupled with two-dimensional liquid chromatography-tandem mass spectrometry(2D LC-MS/MS. The differentially expressed proteins identified by iTRAQ were further validated with Western blot.A total of 105 unique proteins present in the three groups were identified, and relative expression data were obtained for 92 of them with high confidence by employing the iTRAQ-based experiments. The downregulation of gelsolin in maternal serum of fetus with CTD was further verified by Western blot.The identification of differentially expressed protein gelsolin in the serum of the pregnant women carrying a CTD fetus by using proteomic technology may be able to serve as a foundation to further explore the biomarker for detection of CTD fetus from the maternal serum.

Clinical characteristics and SAP scintigraphic findings in 10 patients with AGel amyloidosis.

Science.gov (United States)

Rowczenio, Dorota; Tennent, Glenys A; Gilbertson, Janet; Lachmann, Helen J; Hutt, David F; Bybee, Alison; Hawkins, Philip N; Gillmore, Julian D

2014-12-01

The clinical features of hereditary gelsolin (AGel) amyloidosis include corneal lattice dystrophy, distal sensorimotor, cranial neuropathy and cutis laxa. To date, four mutations of the gelsolin (GSN) gene encoding the following variants have been identified as the cause of this malady; p.D214N, p.D214Y, p.G194R and p.N211K (this nomenclature includes the 27-residue signal peptide). Interestingly, the latter two variants are associated exclusively with a renal amyloidosis phenotype. Here we report the clinical features in 10 patients with AGel amyloidosis associated with the p.D214N mutation, all of whom underwent whole body (123)I-SAP scintigraphy and were followed up in a single UK Centre for a prolonged period. Two patients, from the same kindred presented with proteinuria; eight subjects had a characteristic AGel amyloidosis phenotype including cranial neuropathy and/or corneal lattice dystrophy. (123)I-SAP scintigraphy revealed substantial renal amyloid deposits in all 10 patients, including those with preserved renal function, and usually without tracer uptake into other visceral organs. (123)I-SAP scintigraphy is a non-invasive technique that aids early diagnosis of patients with this rare disease, especially those who lack a family history and/or present with an unusual clinical phenotype.

Histone acetylation and CREB binding protein are required for neuronal resistance against ischemic injury.

Directory of Open Access Journals (Sweden)

Ferah Yildirim

Full Text Available Epigenetic transcriptional regulation by histone acetylation depends on the balance between histone acetyltransferase (HAT and deacetylase activities (HDAC. Inhibition of HDAC activity provides neuroprotection, indicating that the outcome of cerebral ischemia depends crucially on the acetylation status of histones. In the present study, we characterized the changes in histone acetylation levels in ischemia models of focal cerebral ischemia and identified cAMP-response element binding protein (CREB-binding protein (CBP as a crucial factor in the susceptibility of neurons to ischemic stress. Both neuron-specific RNA interference and neurons derived from CBP heterozygous knockout mice showed increased damage after oxygen-glucose deprivation (OGD in vitro. Furthermore, we demonstrated that ischemic preconditioning by a short (5 min subthreshold occlusion of the middle cerebral artery (MCA, followed 24 h afterwards by a 30 min occlusion of the MCA, increased histone acetylation levels in vivo. Ischemic preconditioning enhanced CBP recruitment and histone acetylation at the promoter of the neuroprotective gene gelsolin leading to increased gelsolin expression in neurons. Inhibition of CBP's HAT activity attenuated neuronal ischemic preconditioning. Taken together, our findings suggest that the levels of CBP and histone acetylation determine stroke outcome and are crucially associated with the induction of an ischemia-resistant state in neurons.

Progressive Pigmentary Purpura

Science.gov (United States)

... Category: Share: Yes No, Keep Private Progressive Pigmentary Purpura Share | Progressive pigmentary purpura (we will call it PPP) is a group ... conditions ( Schamberg's disease , Lichenoid dermatitis of Gourgerot-Blum, purpura annularis telangiectodes of Majocchi and Lichen aureus). Schamberg's ...

The cleavage product of amyloid-β protein precursor sAβPPα modulates BAG3-dependent aggresome formation and enhances cellular proteasomal activity.

Science.gov (United States)

Renziehausen, Jana; Hiebel, Christof; Nagel, Heike; Kundu, Arpita; Kins, Stefan; Kögel, Donat; Behl, Christian; Hajieva, Parvana

2015-01-01

Alzheimer's disease (AD) is the major age-associated form of dementia characterized by gradual cognitive decline. Aberrant cleavage of the amyloid-β protein precursor (AβPP) is thought to play an important role in the pathology of this disease. Two principal AβPP processing pathways exist: amyloidogenic cleavage of AβPP resulting in production of the soluble N-terminal fragment sAβPPβ, amyloid-β (Aβ), which accumulates in AD brain, and the AβPP intracellular domain (AICD) sAβPPα, p3 and AICD are generated in the non-amyloidogenic pathway. Prevalence of amyloidogenic versus non-amyloidogenic processing leads to depletion of sAβPPα and an increase in Aβ. Although sAβPPα is a well-accepted neurotrophic protein, molecular effects of this fragment remains unknown. Different studies reported impaired protein degradation pathways in AD brain, pointing to a role of disturbed proteasomal activity in the pathogenesis of this disease. Here we studied the possible role of sAβPPα in Bag3-mediated selective macroautophagy and proteasomal degradation. Employing human IMR90 cells, HEK 293 cells, and primary neurons, we demonstrate that sAβPPα prevents the proteotoxic stress-induced increase of Bag3 at the protein and at the mRNA level indicating a transcriptional regulation. Intriguingly, p62 and LC3, two other key players of autophagy, were not affected. Moreover, the formation and the accumulation of disease-related protein aggregates were significantly reduced by sAβPPα. Interestingly, there was a significant increase of proteasomal activity by sAβPPα as demonstrated by using various proteasome substrates. Our findings demonstrate that sAβPPα modulates Bag3 expression, aggresome formation, and proteasomal activity, thereby providing first evidence for a function of sAβPPα in the regulation of proteostasis.

Progressive geometric algorithms

NARCIS (Netherlands)

Alewijnse, S.P.A.; Bagautdinov, T.M.; de Berg, M.T.; Bouts, Q.W.; ten Brink, Alex P.; Buchin, K.A.; Westenberg, M.A.

2015-01-01

Progressive algorithms are algorithms that, on the way to computing a complete solution to the problem at hand, output intermediate solutions that approximate the complete solution increasingly well. We present a framework for analyzing such algorithms, and develop efficient progressive algorithms

Progressive geometric algorithms

NARCIS (Netherlands)

Alewijnse, S.P.A.; Bagautdinov, T.M.; Berg, de M.T.; Bouts, Q.W.; Brink, ten A.P.; Buchin, K.; Westenberg, M.A.

2014-01-01

Progressive algorithms are algorithms that, on the way to computing a complete solution to the problem at hand, output intermediate solutions that approximate the complete solution increasingly well. We present a framework for analyzing such algorithms, and develop efficient progressive algorithms

Work in Progress: Gender and Politics in Late Elizabethan Progress Entertainments

Science.gov (United States)

Kolkovich, Elizabeth Zeman

2009-01-01

This dissertation analyzes the understudied dramatic genre of Elizabethan progress entertainments, the political ideologies it conveys, and especially the female alliances it enacts. Aristocrats staged these outdoor, episodic pageants on their country estates during Elizabeth I's summer "progress" visits, 1575-1602. While previous scholars…

Geothermal progress monitor. Progress report No. 1

Energy Technology Data Exchange (ETDEWEB)

1979-12-01

Progress is reported on the following: electrical uses, direct-heat uses, drilling activities, leases, geothermal loan guarantee program, general activities, and legal, institutional, and regulatory activites. (MHR)

Pathway-based analysis of genome-wide siRNA screens reveals the regulatory landscape of APP processing.

Directory of Open Access Journals (Sweden)

Luiz Miguel Camargo

Full Text Available The progressive aggregation of Amyloid-β (Aβ in the brain is a major trait of Alzheimer's Disease (AD. Aβ is produced as a result of proteolytic processing of the β-amyloid precursor protein (APP. Processing of APP is mediated by multiple enzymes, resulting in the production of distinct peptide products: the non-amyloidogenic peptide sAPPα and the amyloidogenic peptides sAPPβ, Aβ40, and Aβ42. Using a pathway-based approach, we analyzed a large-scale siRNA screen that measured the production of different APP proteolytic products. Our analysis identified many of the biological processes/pathways that are known to regulate APP processing and have been implicated in AD pathogenesis, as well as revealing novel regulatory mechanisms. Furthermore, we also demonstrate that some of these processes differentially regulate APP processing, with some mechanisms favouring production of certain peptide species over others. For example, synaptic transmission having a bias towards regulating Aβ40 production over Aβ42 as well as processes involved in insulin and pancreatic biology having a bias for sAPPβ production over sAPPα. In addition, some of the pathways identified as regulators of APP processing contain genes (CLU, BIN1, CR1, PICALM, TREM2, SORL1, MEF2C, DSG2, EPH1A recently implicated with AD through genome wide association studies (GWAS and associated meta-analysis. In addition, we provide supporting evidence and a deeper mechanistic understanding of the role of diabetes in AD. The identification of these processes/pathways, their differential impact on APP processing, and their relationships to each other, provide a comprehensive systems biology view of the "regulatory landscape" of APP.

Progress test utopia.

Science.gov (United States)

van der Vleuten, Cees; Freeman, Adrian; Collares, Carlos Fernando

2018-04-01

This paper discusses the advantages of progress testing. A utopia is described where medical schools would work together to develop and administer progress testing. This would lead to a significant reduction of cost, an increase in the quality of measurement and phenomenal feedback to learner and school. Progress testing would also provide more freedom and resources for more creative in-school assessment. It would be an educationally attractive alternative for the creation of cognitive licensing exams. A utopia is always far away in the future, but by formulating a vision for that future we may engage in discussions on how to get there.

Setting a research agenda for progressive multiple sclerosis: the International Collaborative on Progressive MS.

Science.gov (United States)

Fox, Robert J; Thompson, Alan; Baker, David; Baneke, Peer; Brown, Doug; Browne, Paul; Chandraratna, Dhia; Ciccarelli, Olga; Coetzee, Timothy; Comi, Giancarlo; Feinstein, Anthony; Kapoor, Raj; Lee, Karen; Salvetti, Marco; Sharrock, Kersten; Toosy, Ahmed; Zaratin, Paola; Zuidwijk, Kim

2012-11-01

Despite significant progress in the development of therapies for relapsing MS, progressive MS remains comparatively disappointing. Our objective, in this paper, is to review the current challenges in developing therapies for progressive MS and identify key priority areas for research. A collaborative was convened by volunteer and staff leaders from several MS societies with the mission to expedite the development of effective disease-modifying and symptom management therapies for progressive forms of multiple sclerosis. Through a series of scientific and strategic planning meetings, the collaborative identified and developed new perspectives on five key priority areas for research: experimental models, identification and validation of targets and repurposing opportunities, proof-of-concept clinical trial strategies, clinical outcome measures, and symptom management and rehabilitation. Our conclusions, tackling the impediments in developing therapies for progressive MS will require an integrated, multi-disciplinary approach to enable effective translation of research into therapies for progressive MS. Engagement of the MS research community through an international effort is needed to address and fund these research priorities with the ultimate goal of expediting the development of disease-modifying and symptom-relief treatments for progressive MS.

Setting a research agenda for progressive multiple sclerosis: The International Collaborative on Progressive MS

Science.gov (United States)

Thompson, Alan; Baker, David; Baneke, Peer; Brown, Doug; Browne, Paul; Chandraratna, Dhia; Ciccarelli, Olga; Coetzee, Timothy; Comi, Giancarlo; Feinstein, Anthony; Kapoor, Raj; Lee, Karen; Salvetti, Marco; Sharrock, Kersten; Toosy, Ahmed; Zaratin, Paola; Zuidwijk, Kim

2012-01-01

Despite significant progress in the development of therapies for relapsing MS, progressive MS remains comparatively disappointing. Our objective, in this paper, is to review the current challenges in developing therapies for progressive MS and identify key priority areas for research. A collaborative was convened by volunteer and staff leaders from several MS societies with the mission to expedite the development of effective disease-modifying and symptom management therapies for progressive forms of multiple sclerosis. Through a series of scientific and strategic planning meetings, the collaborative identified and developed new perspectives on five key priority areas for research: experimental models, identification and validation of targets and repurposing opportunities, proof-of-concept clinical trial strategies, clinical outcome measures, and symptom management and rehabilitation. Our conclusions, tackling the impediments in developing therapies for progressive MS will require an integrated, multi-disciplinary approach to enable effective translation of research into therapies for progressive MS. Engagement of the MS research community through an international effort is needed to address and fund these research priorities with the ultimate goal of expediting the development of disease-modifying and symptom-relief treatments for progressive MS. PMID:22917690

Progress Report 1994

International Nuclear Information System (INIS)

1995-01-01

This document is the 1994 annual progress report of the CEA-Direction of Waste Management (DGD). It comprises four chapters. The first chapter is a general presentation of radioactive wastes, of the management of liquid effluents, solid wastes, sealed sources, of the relations with the ANDRA (The French Agency for the Management of Radioactive Wastes), and of the research and development studies in progress for the improvement of waste management. The second chapter concerns the spent fuels and their reprocessing, in particular AGR and PWR type reactor fuels, the ''Caramel'' fuel from Osiris reactor and the cover elements from the Rapsodie reactor core. The long time storage of ancient fuels is also discussed. The third chapter concerns the dismantling of decommissioned installations, the actions in progress and the planning of dismantling actions up to the year 2000. Chapter four is devoted to the management of wastes from the Direction of Military Applications (DAM), the actions in progress in the different DAM centers and the cleansing projects at Marcoule plant. (J.S.). 5 figs., 28 tabs., 21 photos., 3 appendix

White Matter Lesion Progression in LADIS

DEFF Research Database (Denmark)

Schmidt, Reinhold; Berghold, Andrea; Jokinen, Hanna

2012-01-01

BACKGROUND AND PURPOSE: White matter lesion (WML) progression has been advocated as a surrogate marker in intervention trials on cerebral small vessel disease. We assessed the rate of visually rated WML progression, studied correlations between lesion progression and cognition, and estimated sample...... sizes for clinical trials with pure WML progression vs combined WML progression-cognitive outcomes. METHODS: Those 394 participants of the Leukoaraiosis and Disability Study (LADIS) study with magnetic resonance imaging scanning at baseline and 3-year follow-up were analyzed. WML progression rating...

Association for Progressive Communication : Institutional ...

International Development Research Centre (IDRC) Digital Library (Canada)

Monitoring Progress Toward the Information Society : Digital Divide Index. Orbicom's Digital Divide Index is a rigorous statistical tool for benchmarking access to and use of information and communication technologies (ICT), and monitoring progress toward the... View moreMonitoring Progress Toward the Information ...

Does a Progressive PIT Stabilize the Economy? A Comparison of Progressive and Flat Taxes

Directory of Open Access Journals (Sweden)

Krajewski Piotr

2017-03-01

Full Text Available The aim of the article is to examine the impact of progressive personal income tax rates and the effectiveness of this tax as an automatic economic stabilizer. The assessment of automatic stabilizers is based on the estimates of tax cyclical components. The study shows that the output elasticity of PIT is higher than one, which means that the analysed tax acts relatively efficiently as an automatic stabilizer. However, it was also observed that the tax progressivity is not the main reason of the effectiveness of a progressive PIT as an automatic stabilizer. The study shows that changes in progressive rates of PIT, contrary to widespread opinions, have little effect on the effectiveness of passive fiscal policy. Personal income tax acts as automatic stabilizer mostly due not to the progressive tax rates, but because of the sensitivity of employment to GDP fluctuations.

Progression og underviserkompetencer

Directory of Open Access Journals (Sweden)

Lene Tortzen Bager

2014-03-01

Full Text Available På baggrund af en kvalitativ interviewundersøgelse af undervisere ved Aarhus Universitet lavet i 2012, tematiserer artiklen, hvordan undervisere udvikler deres faglige og pædagogiske kompetencer i forhold til at kunne skabe progression inden for innovation og entreprenørskab forstået enten som didaktik, arbejdsformer i faglige forløb eller som fag på universitetet. I arbejdet med progression er det en udfordring at integrere de nye faglige dimensioner i det kernefaglige felt. Den seneste model for progression inden for innovation og entreprenør-skab siger, at det er den lærendes generelle erfaringsniveau, der er den afgørende progressionsskabende faktor (Progressionsmodellen, Fonden for Entreprenørskab, 2013b. Samtidig skelner international forskning inden for studiekompetenceområdet mellem niveauer, hvor indlejret viden er det mest avancerede kompetenceniveau (Barrie, 2002.Ifølge progressionsmodellen og den nævnte kompetenceforskning er erfaring og dybt integreret læring altså centrale dimensioner i progression. Men hvad er underviserens rolle heri? Underviserens professionelle udviklingsarbejde forekommer at være underbelyst i forhold til, at underviseren er den legitime garant for integrationen af nye faglige dimensioner og for den studerendes kompetenceniveau. Interviewundersøgelsen forholder sig til spørgsmålet om progression gennem de deltagende underviseres beskrivelse af betydningslag i entreprenørskabsbegrebet koblet til de praksisformer i undervisningen, der knytter sig hertil samt et indblik i undervisernes refleksioner over deres kompetenceudviklingsprocesser. Artiklens bidrag til progression er at se underviserens motivation og kompetenceudvikling som forudsætninger herfor.     Based on a qualitative study of five teachers in the Faculty of Arts at Aarhus University that took place during 2012, the article thematizes how teachers develop their professional and educational qualifications in innovation and

Arsenic trioxide (AT) is a novel human neutrophil pro-apoptotic agent: effects of catalase on AT-induced apoptosis, degradation of cytoskeletal proteins and de novo protein synthesis.

Science.gov (United States)

Binet, François; Cavalli, Hélène; Moisan, Eliane; Girard, Denis

2006-02-01

The anti-cancer drug arsenic trioxide (AT) induces apoptosis in a variety of transformed or proliferating cells. However, little is known regarding its ability to induce apoptosis in terminally differentiated cells, such as neutrophils. Because neutropenia has been reported in some cancer patients after AT treatment, we hypothesised that AT could induce neutrophil apoptosis, an issue that has never been investigated. Herein, we found that AT-induced neutrophil apoptosis and gelsolin degradation via caspases. AT did not increase neutrophil superoxide production and did not induce mitochondrial generation of reactive oxygen species. AT-induced apoptosis in PLB-985 and X-linked chronic granulomatous disease (CGD) cells (PLB-985 cells deficient in gp91(phox) mimicking CGD) at the same potency. Addition of catalase, an inhibitor of H2O2, reversed AT-induced apoptosis and degradation of the cytoskeletal proteins gelsolin, alpha-tubulin and lamin B1. Unexpectedly, AT-induced de novo protein synthesis, which was reversed by catalase. Cycloheximide partially reversed AT-induced apoptosis. We conclude that AT induces neutrophil apoptosis by a caspase-dependent mechanism and via de novo protein synthesis. H2O2 is of major importance in AT-induced neutrophil apoptosis but its production does not originate from nicotinamide adenine dinucleotide phosphate dehydrogenase activation and mitochondria. Cytoskeletal structures other than microtubules can now be considered as novel targets of AT.

Docosahexaenoic Acid Reduces Amyloid β Production via Multiple Pleiotropic Mechanisms*

Science.gov (United States)

Grimm, Marcus O. W.; Kuchenbecker, Johanna; Grösgen, Sven; Burg, Verena K.; Hundsdörfer, Benjamin; Rothhaar, Tatjana L.; Friess, Petra; de Wilde, Martijn C.; Broersen, Laus M.; Penke, Botond; Péter, Mária; Vígh, László; Grimm, Heike S.; Hartmann, Tobias

2011-01-01

Alzheimer disease is characterized by accumulation of the β-amyloid peptide (Aβ) generated by β- and γ-secretase processing of the amyloid precursor protein (APP). The intake of the polyunsaturated fatty acid docosahexaenoic acid (DHA) has been associated with decreased amyloid deposition and a reduced risk in Alzheimer disease in several epidemiological trials; however, the exact underlying molecular mechanism remains to be elucidated. Here, we systematically investigate the effect of DHA on amyloidogenic and nonamyloidogenic APP processing and the potential cross-links to cholesterol metabolism in vivo and in vitro. DHA reduces amyloidogenic processing by decreasing β- and γ-secretase activity, whereas the expression and protein levels of BACE1 and presenilin1 remain unchanged. In addition, DHA increases protein stability of α-secretase resulting in increased nonamyloidogenic processing. Besides the known effect of DHA to decrease cholesterol de novo synthesis, we found cholesterol distribution in plasma membrane to be altered. In the presence of DHA, cholesterol shifts from raft to non-raft domains, and this is accompanied by a shift in γ-secretase activity and presenilin1 protein levels. Taken together, DHA directs amyloidogenic processing of APP toward nonamyloidogenic processing, effectively reducing Aβ release. DHA has a typical pleiotropic effect; DHA-mediated Aβ reduction is not the consequence of a single major mechanism but is the result of combined multiple effects. PMID:21324907

Demyelination versus remyelination in progressive multiple sclerosis

DEFF Research Database (Denmark)

Bramow, Stephan; Frischer, Josa M; Lassmann, Hans

2010-01-01

The causes of incomplete remyelination in progressive multiple sclerosis are unknown, as are the pathological correlates of the different clinical characteristics of patients with primary and secondary progressive disease. We analysed brains and spinal cords from 51 patients with progressive...... multiple sclerosis by planimetry. Thirteen patients with primary progressive disease were compared with 34 with secondary progressive disease. In patients with secondary progressive multiple sclerosis, we found larger brain plaques, more demyelination in total and higher brain loads of active demyelination...... compared with patients with primary progressive disease. In addition, the brain density of plaques with high-grade inflammation and active demyelination was highest in secondary progressive multiple sclerosis and remained ~18% higher than in primary progressive multiple sclerosis after adjustments...

Progress as Compositional Lock-Freedom

DEFF Research Database (Denmark)

Carbone, Marco; Dardha, Ornela; Montesi, Fabrizio

2014-01-01

A session-based process satisfies the progress property if its sessions never get stuck when it is executed in an adequate context. Previous work studied how to define progress by introducing the notion of catalysers, execution contexts generated from the type of a process. In this paper, we refine...... such definition to capture a more intuitive notion of context adequacy for checking progress. Interestingly, our new catalysers lead to a novel characterisation of progress in terms of the standard notion of lock-freedom. Guided by this discovery, we also develop a conservative extension of catalysers that does...

Progression from acute to chronic pancreatitis

DEFF Research Database (Denmark)

Nøjgaard, Camilla; Becker, Ulrik; Matzen, Peter

2011-01-01

Objectives: Knowledge of the natural course of acute pancreatitis (AP) and risk of progression to chronic pancreatitis (CP) is limited. The aims were to describe: (1) the incidence of progression from AP to CP, (2) prognostic factors for progression, and (3) the natural course and mortality.......1%) during follow-up; 48.2% developed from alcoholic AP, 47.0% from idiopathic AP, and 4.8% from other causes. The mortality rate for patients with progressive AP was 2.7 times higher than in patients with nonprogressive acute pancreatitis, and 5.3 to 6.5 times higher than in the background population....... In Cox regression analyses corrected for age, only smoking was of significance for the progression from AP to CP. Conclusions: Acute pancreatitis can progress to CP, not only from alcoholic but also from nonalcoholic AP. Smoking was the strongest risk factor associated with progression. The mortality...

Waste management progress report

International Nuclear Information System (INIS)

1997-06-01

During the Cold War era, when DOE and its predecessor agencies produced nuclear weapons and components, and conducted nuclear research, a variety of wastes were generated (both radioactive and hazardous). DOE now has the task of managing these wastes so that they are not a threat to human health and the environment. This document is the Waste Management Progress Report for the U.S. Department of Energy dated June 1997. This progress report contains a radioactive and hazardous waste inventory and waste management program mission, a section describing progress toward mission completion, mid-year 1997 accomplishments, and the future outlook for waste management

Opportunities for Collaborative Adaptive Management Progress: Integrating Stakeholder Assessments into Progress Measurement

Directory of Open Access Journals (Sweden)

Jim Berkley

2013-12-01

There are differences among stakeholders in the indicators they consider as relevant to the assessment of progress. Elucidating these differences can provide useful information about system components and relationships that are important to public support of a CAM program and progress. One of the sources of differences in progress assessments among stakeholders comes from their diverse perceptions about the desired and current states of the social-ecological systems. Stakeholder behavior can be inconsistent between group and individual settings. Individually they may make plans, based on their assessments, that do not conform to the group plan because of their unique interests and preferences. The results of this study need to be further tested. The framework should be used through multiple cycles to determine whether the information gathered with this approach results in additional progress as compared with past approaches. In particular, it would be helpful to test whether gathering such information resulted in a decrease in stakeholders electing to go outside of the CAM process to get their needs met.

Scientific progress as increasing verisimilitude.

Science.gov (United States)

Niiniluoto, Ilkka

2014-06-01

According to the foundationalist picture, shared by many rationalists and positivist empiricists, science makes cognitive progress by accumulating justified truths. Fallibilists, who point out that complete certainty cannot be achieved in empirical science, can still argue that even successions of false theories may progress toward the truth. This proposal was supported by Karl Popper with his notion of truthlikeness or verisimilitude. Popper's own technical definition failed, but the idea that scientific progress means increasing truthlikeness can be expressed by defining degrees of truthlikeness in terms of similarities between states of affairs. This paper defends the verisimilitude approach against Alexander Bird who argues that the "semantic" definition (in terms of truth or truthlikeness alone) is not sufficient to define progress, but the "epistemic" definition referring to justification and knowledge is more adequate. Here Bird ignores the crucial distinction between real progress and estimated progress, explicated by the difference between absolute (and usually unknown) degrees of truthlikeness and their evidence-relative expected values. Further, it is argued that Bird's idea of returning to the cumulative model of growth requires an implausible trick of transforming past false theories into true ones.

Involvement of receptor tyrosine kinase Tyro3 in amyloidogenic APP processing and β-amyloid deposition in Alzheimer's disease models.

Directory of Open Access Journals (Sweden)

Yan Zheng

Full Text Available Alzheimer's disease (AD is the most common progressive neurodegenerative disease known to humankind. It is characterized by brain atrophy, extracellular amyloid plaques, and intracellular neurofibril tangles. β-Amyloid cascade is considered the major causative player in AD. Up until now, the mechanisms underlying the process of Aβ generation and accumulation in the brain have not been well understood. Tyro3 receptor belongs to the TAM receptor subfamily of receptor protein tyrosine kinases (RPTKs. It is specifically expressed in the neurons of the neocortex and hippocampus. In this study, we established a cell model stably expressing APPswe mutants and producing Aβ. We found that overexpression of Tyro3 receptor in the cell model significantly decreased Aβ generation and also down-regulated the expression of β-site amyloid precursor protein cleaving enzyme (BACE1. However, the effects of Tyro3 were inhibited by its natural ligand, Gas6, in a concentration-dependent manner. In order to confirm the role of Tyro3 in the progression of AD development, we generated an AD transgenic mouse model accompanied by Tyro3 knockdown. We observed a significant increase in the number of amyloid plaques in the hippocampus in the mouse model. More plaque-associated clusters of astroglia were also detected. The present study may help researchers determine the role of Tyro3 receptor in the neuropathology of AD.

Discovering biological progression underlying microarray samples.

Directory of Open Access Journals (Sweden)

Peng Qiu

2011-04-01

Full Text Available In biological systems that undergo processes such as differentiation, a clear concept of progression exists. We present a novel computational approach, called Sample Progression Discovery (SPD, to discover patterns of biological progression underlying microarray gene expression data. SPD assumes that individual samples of a microarray dataset are related by an unknown biological process (i.e., differentiation, development, cell cycle, disease progression, and that each sample represents one unknown point along the progression of that process. SPD aims to organize the samples in a manner that reveals the underlying progression and to simultaneously identify subsets of genes that are responsible for that progression. We demonstrate the performance of SPD on a variety of microarray datasets that were generated by sampling a biological process at different points along its progression, without providing SPD any information of the underlying process. When applied to a cell cycle time series microarray dataset, SPD was not provided any prior knowledge of samples' time order or of which genes are cell-cycle regulated, yet SPD recovered the correct time order and identified many genes that have been associated with the cell cycle. When applied to B-cell differentiation data, SPD recovered the correct order of stages of normal B-cell differentiation and the linkage between preB-ALL tumor cells with their cell origin preB. When applied to mouse embryonic stem cell differentiation data, SPD uncovered a landscape of ESC differentiation into various lineages and genes that represent both generic and lineage specific processes. When applied to a prostate cancer microarray dataset, SPD identified gene modules that reflect a progression consistent with disease stages. SPD may be best viewed as a novel tool for synthesizing biological hypotheses because it provides a likely biological progression underlying a microarray dataset and, perhaps more importantly, the

A beta2-microglobulin cleavage variant fibrillates at near-physiological pH

DEFF Research Database (Denmark)

Corlin, Dorthe B; Johnsen, Christina K; Nissen, Mogens H

2009-01-01

Beta2-microglobulin (beta2m) deposits as amyloid in dialysis-related amyloidosis (DRA), predominantly in joints. The molecular mechanisms underlying the amyloidogenicity of beta2m are still largely unknown. In vitro, acidic conditions, pH ... several days. Here, we show that amyloid fibrils are generated in less than an hour when a cleavage variant of beta2m--found in the circulation of many dialysis patients--is exposed to pH levels (pH 6.6) occurring in joints during inflammation. Aggregation and fibrillation, including seeding effects...... with intact, native beta2m were studied by Thioflavin T fluorescence spectroscopy, turbidimetry, capillary electrophoresis, and electron microscopy. We conclude that a biologically relevant variant of beta2m is amyloidogenic at slightly acidic pH. Also, only a very small amount of preformed fibrils...

Physicians’ Progress Notes

DEFF Research Database (Denmark)

Bansler, Jørgen; Havn, Erling C.; Mønsted, Troels

2013-01-01

in patient care, they have not dealt specifically with the role, structure, and content of the progress notes. As a consequence, CSCW research has not yet taken fully into account the fact that progress notes are coordinative artifacts of a rather special kind, an open-ended chain of prose texts, written...... sequentially by cooperating physicians for their own use as well as for that of their colleagues. We argue that progress notes are the core of the medical record, in that they marshal and summarize the overwhelming amount of data that is available in the modern hospital environment, and that their narrative...... format is uniquely adequate for the pivotal epistemic aspect of cooperative clinical work: the narrative format enables physicians to not only record ‘facts’ but also—by filtering, interpreting, organizing, and qualifying information—to make sense and act concertedly under conditions of uncertainty...

Zolpidem in Progressive Supranuclear Palsy

Directory of Open Access Journals (Sweden)

Sandip K. Dash

2013-01-01

Full Text Available Progressive supranuclear palsy (PSP is a progressive neurodegenerative disorder, characterized by motor symptoms, postural instability, personality changes, and cognitive impairment. There is no effective treatment for this disorder. Reduced neurotransmission of GABA in the striatum and globus pallidus may contribute to the symptoms of motor and cognitive symptoms seen in PSP. Zolpidem is a GABA agonist of the benzodiazepine subreceptor BZ1. Here a nondiabetic, normotensive case of PSP is (Progressive Supranuclear Palsy described, which showed improvement in swallowing, speech, and gaze paresis after zolpidem therapy and possible mechanism of actions are discussed. However, more trials are needed with large number of patients to confirm the effectiveness of zolpidem in progressive supranuclear palsy.

Progress report 1981

International Nuclear Information System (INIS)

Chalupka, A.; Dirninger, G.

1982-01-01

The progress report describes the scientific work and research results of the institute for radium research and nuclear physics of the Austrian Academy of Sciences for the period of 1981. The progress report covers the subject areas of nuclear theory, nuclear model calculations, experimental nuclear physics and neutron involved reactions, medium energy physics, instrumentation and detectors, evaluation of nuclear data and numerical data processing, dating, applications in medicine, dosimetry and environmental studies. A list of publications of this institute is given. (A.N.)

Progress report 1982

International Nuclear Information System (INIS)

Chalupka, A.; Wild, E.; Dirninger, G.

1983-01-01

The progress report describes the scientific work and research results of the institute for radium research and nuclear physics of the Austrian Academy of Sciences for the period of 1982. The progress report covers the subject areas of nuclear theory, nuclear model calculations, experimental nuclear physics and neutron involved reactions, medium energy physics, instrumentation and detectors, evaluation of nuclear data and numerical data processing, dating, applications in medicine, dosimetry and environmental studies. A list of publications of this institute is given. (A.N.)

Progress at LAMPF: Clinton P. Anderson Meson Physics Facility. Progress report, January-June 1981

International Nuclear Information System (INIS)

Allred, J.C.

1981-09-01

Progress at LAMPF is the semiannual progress report of the MP Division of the Los Alamos National Laboratory. The report includes brief reports on research done at LAMPF by researchers from other institutions and Los Alamos divisions

Progress at LAMPF: Clinton P. Anderson Meson Physics Facility. Progress report, January-June 1981

Energy Technology Data Exchange (ETDEWEB)

Allred, J.C. (ed.)

1981-09-01

Progress at LAMPF is the semiannual progress report of the MP Division of the Los Alamos National Laboratory. The report includes brief reports on research done at LAMPF by researchers from other institutions and Los Alamos divisions.

Earnings progression, human capital and incentives

DEFF Research Database (Denmark)

Frederiksen, Anders

progression by investigating the effects of on-the-job human capital acquisition, explicit short-run incentives and career concern incentives on earnings progression. The model leads to predictions about the incentive structure and the progression in both cross-sectional and individual earnings which...

Progress at LAMPF: Clinton P. Anderson Meson Physics Facility. Progress report, July-December 1980

International Nuclear Information System (INIS)

Allred, J.C.

1981-03-01

Progress at LAMPF is the semiannual progress report of the MP Division of the Los Alamos National Laboratory. The report also includes brief reports on research done at LAMPF by researchers from other institutions and Los Alamos divisions

Progressive taxation, income inequality, and happiness.

Science.gov (United States)

Oishi, Shigehiro; Kushlev, Kostadin; Schimmack, Ulrich

2018-01-01

Income inequality has become one of the more widely debated social issues today. The current article explores the role of progressive taxation in income inequality and happiness. Using historical data in the United States from 1962 to 2014, we found that income inequality was substantially smaller in years when the income tax was more progressive (i.e., a higher tax rate for higher income brackets), even when controlling for variables like stock market performance and unemployment rate. Time lag analyses further showed that higher progressive taxation predicted increasingly lower income inequality up to 5 years later. Data from the General Social Survey (1972-2014; N = 59,599) with U.S. residents (hereafter referred to as "Americans") showed that during years with higher progressive taxation rates, less wealthy Americans-those in the lowest 40% of the income distribution-tended to be happier, whereas the richest 20% were not significantly less happy. Mediational analyses confirmed that the association of progressive taxation with the happiness of less wealthy Americans can be explained by lower income inequality in years with higher progressive taxation. A separate sample of Americans polled online (N = 373) correctly predicted the positive association between progressive taxation and the happiness of poorer Americans but incorrectly expected a strong negative association between progressive taxation and the happiness of richer Americans. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Individual moral development and moral progress

OpenAIRE

Schinkel, Anders; de Ruyter, Doret J.

2017-01-01

At first glance, one of the most obvious places to look for moral progress is in individuals, in particular in moral development from childhood to adulthood. In fact, that moral progress is possible is a foundational assumption of moral education. Beyond the general agreement that moral progress is not only possible but even a common feature of human development things become blurry, however. For what do we mean by ‘progress’? And what constitutes moral progress? Does the idea of individual m...

Pregnancy-induced progression of keratoconus.

Science.gov (United States)

Bilgihan, Kamil; Hondur, Ahmet; Sul, Sabahattin; Ozturk, Sertac

2011-09-01

To report eyes with keratoconus that progressed during pregnancy. Seven eyes of 4 patients with progression of keratoconus during pregnancy were included in this study. The mean age of patients and the mean follow-up duration were 29.3 years and 39 months, respectively. Progressive keratoconus was documented with changes in refraction, corneal topography, and rigid gas-permeable lens fitting pattern. Patients with accompanying systemic and ocular diseases associated with keratoconus, uncontrolled atopic disease, and eye rubbing were excluded. Mean increase in spherical equivalent refraction and simulated keratometry values were 1.4 ± 1.1 and 1.1 ± 0.8 diopters, respectively. In eyes wearing rigid gas-permeable lenses, increase in corneal apical touch and decrease in the base curve radius of the best-fitting contact lens were observed. Hormonal changes during pregnancy may affect corneal biomechanics negatively, and pregnancy may be a previously unrecognized risk factor for progression of keratoconus. To our knowledge, this is the first study showing pregnancy-induced keratoconus progression in patients with no accompanying disease.

The Efficient Side of Progressive Income Taxation

OpenAIRE

Corneo, Giacomo

2000-01-01

This paper examines the allocative implications of progressive income taxation when individuals care about their relative income. It shows that tax progressivity might improve efficiency, and the more so in egalitarian economies. Introducing a progressive income tax can yield a Pareto improvement if pre-tax income is evenly distributed. Implementing undistorted choices of working hours requires a progressive tax schedule, and the optimal degree of progressivity decreases with pre-tax income i...

Progressivity of Taxes, Skeweness of Income Distribution and Violations of the Progressive Principle in Income Tax Systems

Directory of Open Access Journals (Sweden)

Edyta Mazurek

2014-06-01

Full Text Available Kakwani and Lambert state the three axioms, which should be respected by an equitable tax system. They also proposed a measurement system to evaluate the violations of the axioms. One of the axioms, axiom 2, formulates the progression principle in income tax systems. Vernizzi and Pellegrino improved the alternative index to evaluate violations concerning the progressive command in a tax system. The main aim of this paper is to compare the two indexes in order to evaluate violations of progressive principle in income tax systém using the real data. We also check how the progressivity of taxes and skewness of income distribution affect the measurement of the progressive principle violation.

Individual moral development and moral progress

NARCIS (Netherlands)

Schinkel, Anders; de Ruyter, Doret J.

At first glance, one of the most obvious places to look for moral progress is in individuals, in particular in moral development from childhood to adulthood. In fact, that moral progress is possible is a foundational assumption of moral education. Beyond the general agreement that moral progress is

Individual Moral Development and Moral Progress

NARCIS (Netherlands)

Schinkel, Anders; de Ruyter, Doret J.

2017-01-01

At first glance, one of the most obvious places to look for moral progress is in individuals, in particular in moral development from childhood to adulthood. In fact, that moral progress is possible is a foundational assumption of moral education. Beyond the general agreement that moral progress is

Progressive Taxation and Tax Morale

OpenAIRE

Philipp Doerrenberg; Andreas Peichl

2010-01-01

As the link between tax compliance and tax morale is found to be robust, finding the determinants of tax morale can help to understand and fight tax evasion. In this paper we analyze the effect of progressive taxation on tax morale in a cross-country approach - which has not been investigated before. Our theoretical analysis leads to two testable predictions. First, an individual's tax morale is higher, the more progressive the tax schedule is. Second, the impact of tax progressivity on tax m...

Early detection of emphysema progression

DEFF Research Database (Denmark)

Gorbunova, Vladlena; Jacobs, Sander S A M; Lo, Pechin

2010-01-01

Emphysema is one of the most widespread diseases in subjects with smoking history. The gold standard method for estimating the severity of emphysema is a lung function test, such as forced expiratory volume in first second (FEV1). However, several clinical studies showed that chest CT scans offer...... more sensitive estimates of emphysema progression. The standard CT densitometric score of emphysema is the relative area of voxels below a threshold (RA). The RA score is a global measurement and reflects the overall emphysema progression. In this work, we propose a framework for estimation of local...... emphysema progression from longitudinal chest CT scans. First, images are registered to a common system of coordinates and then local image dissimilarities are computed in corresponding anatomical locations. Finally, the obtained dissimilarity representation is converted into a single emphysema progression...

Progressive pseudorheumatoid dysplasia

International Nuclear Information System (INIS)

Mampaey, S.; De Schepper, A.; Vanhoenacker, F.; Boven, K.; Hul, W. van

2000-01-01

A rare case of progressive pseudorheumatoid dysplasia (PPD) in a 9-year-old girl is presented. Clinically, chronic painless swollen joints, accompanied by progressive motion restriction and progressive walking difficulties, were found. Radiologically, there was enlargement of the epimetaphyseal portions of the large joints, metacarpal heads, and phalanges, and generalized platyspondyly with irregular delineation of the endplates of the vertebral bodies. The radioclinical features at the peripheral joints were originally misdiagnosed as juvenile rheumatoid arthritis (JRA), and the structural spinal abnormalities were neglected and interpreted as Scheuermann's disease. However, the absence of active inflammatory parameters argues against JRA, whereas the low age of onset of the irregularities at the vertebral endplates is an argument against the diagnosis of Scheuermann's disease. The combination of the dysplastic abnormalities of the spine, with platyspondyly and Scheuermann-like lesions at an unusually low age of onset, and radiological features mimicking JRA of the peripheral joints, is the clue to the diagnosis of this rare autosomal-recessive disease. This case is the first to document the MRI features of PPD of the spine. (orig.)

How curcumin affords effective protection against amyloid fibrillation in insulin?

DEFF Research Database (Denmark)

Rabiee, Atefeh; Ebrahim Habibi, Azadeh; Ghasemi, Atiyeh Ghasemi

2013-01-01

Since the formation of amyloid structures from proteins was recognized in numerous diseases, many efforts have been devoted to the task of finding effective anti-amyloidogenic compounds. In a number of these investigations, the existence of “generic” compounds is implicitly acknowledged. Curcumin...... been shown effectively influenced by micro molar concentrations of curcumin. Under amyloidogenic conditions (pH 2.5 and 37°C), the compound was observed to inhibit fibril formation of insulin in a dose-dependent manner. Moreover, addition of curcumin to the protein incubated in such conditions...... at different time points resulted in reduced amounts of final fibrils. Disaggregation of pre-formed fibrils was also observed upon addition of curcumin, as well as reduction in final fibril amounts after seeding. Overall, this compound appears to be able to interact with native, intermediate and fibrillar...

Progression of motor symptoms in Parkinson's disease

Institute of Scientific and Technical Information of China (English)

Ruiping Xia; Zhi-Hong Mao

2012-01-01

Parkinson's disease (PD) is a chronic progressive neurodegenerative disease that is clinically manifested by a triad of cardinal motor symptoms - rigidity,bradykinesia and tremor - due to loss of dopaminergic neurons.The motor symptoms of PD become progressively worse as the disease advances.PD is also a heterogeneous disease since rigidity and bradykinesia are the major complaints in some patients whereas tremor is predominant in others.In recent years,many studies have investigated the progression of the hallmark symptoms over time,and the cardinal motor symptoms have different rates of progression,with the disease usually progressing faster in patients with rigidity and bradykinesia than in those with predominant tremor.The current treatment regime of dopamine-replacement therapy improves motor symptoms and alleviates disability.Increasing the dosage of dopaminergic medication is commonly used to combat the worsenirtg symptoms.However,the drug-induced involuntary body movements and motor comphcations can significantly contribute to overall disability.Further,none of the currently-available therapies can slow or halt the disease progression.Significant research efforts have been directed towards developing neuroprotective or disease-modifying agents that are intended to slow the progression.In this article,the most recent clinical studies investigating disease progression and current progress on the development of disease-modifying drug trials are reviewed.

Progressive pseudorheumatoid dysplasia misdiagnosed as ...

African Journals Online (AJOL)

Progressive pseudorheumatoid dysplasia misdiagnosed as seronegative juvenile idiopathic arthritis. Ozgur Taspinar, Fatih Kelesoglu, Yasar Keskin, Murat Uludag. Abstract. Background: Progressive pseudorheumatoid dysplasia (PPD) is a rare spondylo- epi-metaphyseal dysplasia (SEMD). It can be confused with juvenile ...

Progression of chronic renal failure.

Science.gov (United States)

Hakim, R M; Lazarus, J M

1989-11-01

Rates of progression of renal failure were calculated for a group of 277 patients who had five or more clinic visits. The goals of therapy in the absence of ongoing immunological processes were control of blood pressure to diastolic pressures less than 85 mm Hg and serum phosphate less than 1.60 mmol/L (5 mg/dL). The mean rate of progression expressed as the slope of the reciprocal creatinine versus time was -0.0054 +/- 0.0009 dL/mg/mo (mean +/- SEM), and the median was -0.00315 dL/mg/mo. Approximately 25% of these patients had rates of progression less than -0.001 dL/mg/mo. The rate of progression was inversely correlated with the creatinine concentration at entry (P less than 0.004) and with the frequency of clinic visits (P less than 0.01). The "renal survival" time from a creatinine of 880 mumol/L (10 mg/dL) to dialysis was 10.0 +/- 1.2 months (mean +/- SEM). These data provide rates of progression for a group of patients without specific dietary intervention but with vigorous control of blood pressure and phosphorus.

Evaluation of keratoconus progression.

Science.gov (United States)

Shajari, Mehdi; Steinwender, Gernot; Herrmann, Kim; Kubiak, Kate Barbara; Pavlovic, Ivana; Plawetzki, Elena; Schmack, Ingo; Kohnen, Thomas

2018-06-01

To define variables for the evaluation of keratoconus progression and to determine cut-off values. In this retrospective cohort study (2010-2016), 265 eyes of 165 patients diagnosed with keratoconus underwent two Scheimpflug measurements (Pentacam) that took place 1 year apart ±3 months. Variables used for keratoconus detection were evaluated for progression and a correlation analysis was performed. By logistic regression analysis, a keratoconus progression index (KPI) was defined. Receiver-operating characteristic curve (ROC) analysis was performed and Youden Index calculated to determine cut-off values. Variables used for keratoconus detection showed a weak correlation with each other (eg, correlation r=0.245 between RPImin and Kmax, pKPI). KPI was defined by logistic regression and consisted of a Pachymin coefficient of -0.78 (p=0.001), a maximum elevation of back surface coefficient of 0.27 and coefficient of corneal curvature at the zone 3 mm away from the thinnest point on the posterior corneal surface of -12.44 (both pKPI: D-index had a cut-off of 0.4175 (70.6% sensitivity) and Youden Index of 0.606. Cut-off for KPI was -0.78196 (84.7% sensitivity) and a Youden Index of 0.747; both 90% specificity. Keratoconus progression should be defined by evaluating parameters that consider several corneal changes; we suggest D-index and KPI to detect progression. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Motor Speech Phenotypes of Frontotemporal Dementia, Primary Progressive Aphasia, and Progressive Apraxia of Speech

Science.gov (United States)

Poole, Matthew L.; Brodtmann, Amy; Darby, David; Vogel, Adam P.

2017-01-01

Purpose: Our purpose was to create a comprehensive review of speech impairment in frontotemporal dementia (FTD), primary progressive aphasia (PPA), and progressive apraxia of speech in order to identify the most effective measures for diagnosis and monitoring, and to elucidate associations between speech and neuroimaging. Method: Speech and…

Primary progressive aphasia and apraxia of speech.

Science.gov (United States)

Jung, Youngsin; Duffy, Joseph R; Josephs, Keith A

2013-09-01

Primary progressive aphasia is a neurodegenerative syndrome characterized by progressive language dysfunction. The majority of primary progressive aphasia cases can be classified into three subtypes: nonfluent/agrammatic, semantic, and logopenic variants. Each variant presents with unique clinical features, and is associated with distinctive underlying pathology and neuroimaging findings. Unlike primary progressive aphasia, apraxia of speech is a disorder that involves inaccurate production of sounds secondary to impaired planning or programming of speech movements. Primary progressive apraxia of speech is a neurodegenerative form of apraxia of speech, and it should be distinguished from primary progressive aphasia given its discrete clinicopathological presentation. Recently, there have been substantial advances in our understanding of these speech and language disorders. The clinical, neuroimaging, and histopathological features of primary progressive aphasia and apraxia of speech are reviewed in this article. The distinctions among these disorders for accurate diagnosis are increasingly important from a prognostic and therapeutic standpoint. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Modeling Progress in AI

OpenAIRE

Brundage, Miles

2015-01-01

Participants in recent discussions of AI-related issues ranging from intelligence explosion to technological unemployment have made diverse claims about the nature, pace, and drivers of progress in AI. However, these theories are rarely specified in enough detail to enable systematic evaluation of their assumptions or to extrapolate progress quantitatively, as is often done with some success in other technological domains. After reviewing relevant literatures and justifying the need for more ...

Scientific Progress in Strategic Management

DEFF Research Database (Denmark)

Foss, Nicolai Juul

Does the RBV represent a case of scientific progress? And has it emerged as the dominant approach to the analysis of competitive advantage for this reason? Conventional criteria for scientific progress, notably those of the growth of knowledge literature, are not particularly helpful for understa...

Progressive cerebral atrophy in neuromyelitis optica.

Science.gov (United States)

Warabi, Yoko; Takahashi, Toshiyuki; Isozaki, Eiji

2015-12-01

We report two cases of neuromyelitis optica patients with progressive cerebral atrophy. The patients exhibited characteristic clinical features, including elderly onset, secondary progressive tetraparesis and cognitive impairment, abnormally elevated CSF protein and myelin basic protein levels, and extremely highly elevated serum anti-AQP-4 antibody titer. Because neuromyelitis optica pathology cannot switch from an inflammatory phase to the degenerative phase until the terminal phase, neuromyelitis optica rarely appears as a secondary progressive clinical course caused by axonal degeneration. However, severe intrathecal inflammation and massive destruction of neuroglia could cause a secondary progressive clinical course associated with cerebral atrophy in neuromyelitis optica patients. © The Author(s), 2015.

Lifestyle modification and progressive renal failure.

Science.gov (United States)

Ritz, Eberhard; Schwenger, Vedat

2005-08-01

There is increasing evidence that lifestyle factors impact on the risk of developing chronic kidney disease (CKD) and the risk of progression of CKD. Equally important is the consideration that patients with CKD are more likely to die from cardiovascular disease than to reach the stage of end-stage renal failure. It is advantageous that manoeuvres that interfere with progression at the same time also reduce the risk of cardiovascular events. Lifestyle factors that aggravate progression include, among others, smoking, obesity and dietary salt intake. Alcohol consumption, according to some preliminary information, has a bimodal relationship to cardiovascular risk and progression, with moderate consumption being protective.

Periodic progress report, 6 months

DEFF Research Database (Denmark)

Juhl, Thomas Winther; Nielsen, Jakob Skov

This is the first progress report of the BriteEuram project named "High Power Laser Cutting for Heavy Industry" ("Powercut"). The report contains a summary of the objectives of the first period, an overview of the technical progress, a comparison between the planed and the accomplished work...

Progressive Collapse of High-Rise Buildings from Fire

Directory of Open Access Journals (Sweden)

Pershakov Valerii

2016-01-01

Full Text Available Considers ensuring the stability of structures of high-rise buildings against progressive collapse due to fire, proposed measures to ensure the stability of high-rise buildings due to progressive collapse. The analysis of large fires in high-rise buildings with progressive collapse and review of the literature on the issue of progressive collapse. The analysis of the Ukrainian normative documents on progressive collapse resistance.

[Riboflavin UVA crosslinking in progressive keratoconus].

Science.gov (United States)

Maier, P; Reinhard, T

2017-06-01

In patients with keratoconus, a progressive, ectatic disease of the cornea, the shape of the cornea is continuously changing leading to a reduction in visual acuity by progressive myopia and more and more (irregular) astigmatism. The symptomatic treatment consists of the prescription of glasses or special gas-permeable rigid contact lenses. Corneal tomography is generally used for diagnosis. After initial diagnosis of keratoconus, regular tomographic follow-ups should be performed. If clinically significant progression is found and confirmed by repeated measurements, riboflavin UVA collagen crosslinking should be offered to the patients. The aim of riboflavin UVA collagen crosslinking is to halt the progression of the disease to avoid further complications. The therapeutic principle is a combined effect of the photosensitizer riboflavin and UVA light. This stiffening effect of the corneal tissue halts the progression of keratoconus. The efficacy of this treatment has been demonstrated in various randomized, controlled trials.

Glaucoma Monitoring in a Clinical Setting Glaucoma Progression Analysis vs Nonparametric Progression Analysis in the Groningen Longitudinal Glaucoma Study

NARCIS (Netherlands)

Wesselink, Christiaan; Heeg, Govert P.; Jansonius, Nomdo M.

Objective: To compare prospectively 2 perimetric progression detection algorithms for glaucoma, the Early Manifest Glaucoma Trial algorithm (glaucoma progression analysis [GPA]) and a nonparametric algorithm applied to the mean deviation (MD) (nonparametric progression analysis [NPA]). Methods:

Federal Facility Agreement progress report

Energy Technology Data Exchange (ETDEWEB)

1993-10-01

The (SRS) Federal Facility Agreement (FFA) was made effective by the US. Environmental Protection Agency Region IV (EPA) on August 16, 1993. To meet the reporting requirements in Section XXV of the Agreement, the FFA Progress Report was developed. The FFA Progress Report is the first of a series of quarterly progress reports to be prepared by the SRS. As such this report describes the information and action taken to September 30, 1993 on the SRS units identified for investigation and remediation in the Agreement. This includes; rubble pits, runoff basins, retention basin, seepage basin, burning pits, H-Area Tank 16, and spill areas.

Federal Facility Agreement progress report

International Nuclear Information System (INIS)

1993-10-01

The (SRS) Federal Facility Agreement (FFA) was made effective by the US. Environmental Protection Agency Region IV (EPA) on August 16, 1993. To meet the reporting requirements in Section XXV of the Agreement, the FFA Progress Report was developed. The FFA Progress Report is the first of a series of quarterly progress reports to be prepared by the SRS. As such this report describes the information and action taken to September 30, 1993 on the SRS units identified for investigation and remediation in the Agreement. This includes; rubble pits, runoff basins, retention basin, seepage basin, burning pits, H-Area Tank 16, and spill areas

Chronic progressive multiple sclerosis

International Nuclear Information System (INIS)

Buffoli, A.; Micheletti, E.; Capra, R.; Mattioli, F.; Marciano', N.

1991-01-01

A long-lasting immunological suppression action seems to be produced by total lymphoid irradiation; some authors emphasize the favorable effect of this treatment on chronic progressive multiple sclerosis. In order to evaluate the actual role of TLI, 6 patients affected with chronic progressive multiple sclerosis were submitted to TLI with shaped and personalized fields at the Istituto del Radio, University of Brescia, Italy. The total dose delivered was 19.8 Gy in 4 weeks, 1.8 Gy/day, 5d/w; a week elapsed between the first and the second irradiation course. Disability according to Kurtzke scale was evaluated, together with blood lymphocyte count and irradiation side-effects, over a mean follow-up period of 20.8 months (range: 13-24). Our findings indicate that: a) disease progression was not markedly reduced by TLI; b) steroid hormones responsivity was restored after irradiation, and c) side-effects were mild and tolerable

Dissecting the role of disulfide bonds on the amyloid formation of insulin

International Nuclear Information System (INIS)

Li, Yang; Gong, Hao; Sun, Yue; Yan, Juan; Cheng, Biao; Zhang, Xin; Huang, Jing; Yu, Mengying; Guo, Yu; Zheng, Ling; Huang, Kun

2012-01-01

Highlights: ► We dissect how individual disulfide bond affects the amyloidogenicity of insulin. ► A controlled reduction system for insulin is established in this study. ► Disulfide breakage is associated with unfolding and increased amyloidogenicity. ► Breakage of A6-A11 is associated with significantly increased cytotoxicity. ► Analogs without A6-A11 have a higher potency to form high order toxic oligomers. -- Abstract: Disulfide bonds play a critical role in the stability and folding of proteins. Here, we used insulin as a model system, to investigate the role of its individual disulfide bond during the amyloid formation of insulin. Tris(2-carboxyethyl)phosphine (TCEP) was applied to reduce two of the three disulfide bonds in porcine insulin and the reduced disulfide bonds were then alkylated by iodoacetamide. Three disulfide bond-modified insulin analogs, INS-2 (lack of A6-A11), INS-3 (lack of A7-B7) and INS-6 (lack of both A6-A11 and A7-B7), were obtained. Far-UV circular dichroism (CD) spectroscopy results indicated that the secondary structure of INS-2 was the closest to insulin under neutral conditions, followed by INS-3 and INS-6, whereas in an acidic solution all analogs were essentially unfolded. To test how these modifications affect the amyloidogenicity of insulin, thioflavin-T (ThT) fluorescence and transmission electronic microscopy (TEM) were performed. Our results showed that all analogs were more prone to aggregation than insulin, with the order of aggregation rates being INS-6 > INS-3 > INS-2. Cross-linking of unmodified proteins (PICUP) assay results showed that analogs without A6-A11 (INS-2 and INS-6) have a higher potential for oligomerization than insulin and INS-3, which is accompanied with a higher cytotoxicity as the hemolytic assays of human erythrocytes suggested. The results indicated that breakage of A7-B7 induced more unfolding of the insulin structure and a higher amyloidogenicity than breakage of A6-A11, but breakage of A6

Conformational Compatibility Is Essential for Heterologous Aggregation of α-Synuclein

NARCIS (Netherlands)

Sidhu, Arshdeep; Segers-Nolten, Ine; Subramaniam, Vinod

2016-01-01

Under aggregation-prone conditions, soluble amyloidogenic protein monomers can self-assemble into fibrils or they can fibrillize on preformed fibrillar seeds (seeded aggregation). Seeded aggregations are known to propagate the morphology of the seeds in the event of cross-seeding. However, not all

48 CFR 2052.211-71 - Technical progress report.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Technical progress report... Technical progress report. As prescribed at 2011.104-70(b), the contracting officer shall insert the... solicitation. Technical Progress Report (JAN 1993) The contractor shall provide a monthly Technical Progress...

Ceramides in Alzheimer’s Disease: Key Mediators of Neuronal Apoptosis Induced by Oxidative Stress and Aβ Accumulation

Directory of Open Access Journals (Sweden)

Maja Jazvinšćak Jembrek

2015-01-01

Full Text Available Alzheimer’s disease (AD, the most common chronic and progressive neurodegenerative disorder, is characterized by extracellular deposits of amyloid β-peptides (Aβ and intracellular deposits of hyperphosphorylated tau (phospho-tau protein. Ceramides, the major molecules of sphingolipid metabolism and lipid second messengers, have been associated with AD progression and pathology via Aβ generation. Enhanced levels of ceramides directly increase Aβ through stabilization of β-secretase, the key enzyme in the amyloidogenic processing of Aβ precursor protein (APP. As a positive feedback loop, the generated oligomeric and fibrillar Aβ induces a further increase in ceramide levels by activating sphingomyelinases that catalyze the catabolic breakdown of sphingomyelin to ceramide. Evidence also supports important role of ceramides in neuronal apoptosis. Ceramides may initiate a cascade of biochemical alterations, which ultimately leads to neuronal death by diverse mechanisms, including depolarization and permeabilization of mitochondria, increased production of reactive oxygen species (ROS, cytochrome c release, Bcl-2 depletion, and caspase-3 activation, mainly by modulating intracellular signalling, particularly along the pathways related to Akt/PKB kinase and mitogen-activated protein kinases (MAPKs. This review summarizes recent findings related to the role of ceramides in oxidative stress-driven neuronal apoptosis and interplay with Aβ in the cascade of events ending in neuronal degeneration.

End-to-end Structural Restriction of α-Synuclein and Its Influence on Amyloid Fibril Formation

International Nuclear Information System (INIS)

Hong, Chul Suk; Park, Jae Hyung; Choe, Young Jun; Paik, Seung R.

2014-01-01

Relationship between molecular freedom of amyloidogenic protein and its self-assembly into amyloid fibrils has been evaluated with α-synuclein, an intrinsically unfolded protein related to Parkinson's disease, by restricting its structural plasticity through an end-to-end disulfide bond formation between two newly introduced cysteine residues on the N- and C-termini. Although the resulting circular form of α-synuclein exhibited an impaired fibrillation propensity, the restriction did not completely block the protein's interactive core since co-incubation with wild-type α-synuclein dramatically facilitated the fibrillation by producing distinctive forms of amyloid fibrils. The suppressed fibrillation propensity was instantly restored as the structural restriction was unleashed with β-mercaptoethanol. Conformational flexibility of the accreting amyloidogenic protein to pre-existing seeds has been demonstrated to be critical for fibrillar extension process by exerting structural adjustment to a complementary structure for the assembly

End-to-end Structural Restriction of α-Synuclein and Its Influence on Amyloid Fibril Formation

Energy Technology Data Exchange (ETDEWEB)

Hong, Chul Suk; Park, Jae Hyung; Choe, Young Jun; Paik, Seung R. [Seoul National University, Seoul (Korea, Republic of)

2014-09-15

Relationship between molecular freedom of amyloidogenic protein and its self-assembly into amyloid fibrils has been evaluated with α-synuclein, an intrinsically unfolded protein related to Parkinson's disease, by restricting its structural plasticity through an end-to-end disulfide bond formation between two newly introduced cysteine residues on the N- and C-termini. Although the resulting circular form of α-synuclein exhibited an impaired fibrillation propensity, the restriction did not completely block the protein's interactive core since co-incubation with wild-type α-synuclein dramatically facilitated the fibrillation by producing distinctive forms of amyloid fibrils. The suppressed fibrillation propensity was instantly restored as the structural restriction was unleashed with β-mercaptoethanol. Conformational flexibility of the accreting amyloidogenic protein to pre-existing seeds has been demonstrated to be critical for fibrillar extension process by exerting structural adjustment to a complementary structure for the assembly.

Progressive Multifocal Leukoencephalopathy

Science.gov (United States)

... SEARCH Definition Treatment Prognosis Clinical Trials Organizations Publications Definition Progressive multifocal leukoencephalopathy (PML) is a disease of the white matter of the brain, caused by a virus infection ...

Mutations in specific structural regions of immunoglobulin light chains are associated with free light chain levels in patients with AL amyloidosis.

Directory of Open Access Journals (Sweden)

Tanya L Poshusta

Full Text Available BACKGROUND: The amyloidoses are protein misfolding diseases characterized by the deposition of amyloid that leads to cell death and tissue degeneration. In immunoglobulin light chain amyloidosis (AL, each patient has a unique monoclonal immunoglobulin light chain (LC that forms amyloid deposits. Somatic mutations in AL LCs make these proteins less thermodynamically stable than their non-amyloidogenic counterparts, leading to misfolding and ultimately the formation of amyloid fibrils. We hypothesize that location rather than number of non-conservative mutations determines the amyloidogenicity of light chains. METHODOLOGY/PRINCIPAL FINDINGS: We performed sequence alignments on the variable domain of 50 kappa and 91 lambda AL light chains and calculated the number of non-conservative mutations over total number of patients for each secondary structure element in order to identify regions that accumulate non-conservative mutations. Among patients with AL, the levels of circulating immunoglobulin free light chain varies greatly, but even patients with very low levels can have very advanced amyloid deposition. CONCLUSIONS: Our results show that in specific secondary structure elements, there are significant differences in the number of non-conservative mutations between normal and AL sequences. AL sequences from patients with different levels of secreted light chain have distinct differences in the location of non-conservative mutations, suggesting that for patients with very low levels of light chains and advanced amyloid deposition, the location of non-conservative mutations rather than the amount of free light chain in circulation may determine the amyloidogenic propensity of light chains.

SuperB Progress Report: Detector

Energy Technology Data Exchange (ETDEWEB)

Grauges, E.; /Barcelona U., ECM; Donvito, G.; Spinoso, V.; /INFN, Bari /Bari U.; Manghisoni, M.; Re, V.; Traversi, G.; /INFN, Pavia /Bergamo U., Ingengneria Dept.; Eigen, G.; Fehlker, D.; Helleve, L.; /Bergen U.; Carbone, A.; Di Sipio, R.; Gabrielli, A.; Galli, D.; Giorgi, F.; Marconi, U.; Perazzini, S.; Sbarra, C.; Vagnoni, V.; Valentinetti, S.; Villa, M.; Zoccoli, A.; /INFN, Bologna /Bologna U. /Caltech /Carleton U. /Cincinnati U. /INFN, CNAF /INFN, Ferrara /Ferrara U. /UC, Irvine /Taras Shevchenko U. /Orsay, LAL /LBL, Berkeley /UC, Berkeley /Frascati /INFN, Legnaro /Orsay, IPN /Maryland U. /McGill U. /INFN, Milan /Milan U. /INFN, Naples /Naples U. /Novosibirsk, IYF /INFN, Padua /Padua U. /INFN, Pavia /Pavia U. /INFN, Perugia /Perugia U. /INFN, Perugia /Caltech /INFN, Pisa /Pisa U. /Pisa, Scuola Normale Superiore /PNL, Richland /Queen Mary, U. of London /Rutherford /INFN, Rome /Rome U. /INFN, Rome2 /Rome U.,Tor Vergata /INFN, Rome3 /Rome III U. /SLAC /Tel Aviv U. /INFN, Turin /Turin U. /INFN, Padua /Trento U. /INFN, Trieste /Trieste U. /TRIUMF /British Columbia U. /Montreal U. /Victoria U.

2012-02-14

This report describes the present status of the detector design for SuperB. It is one of four separate progress reports that, taken collectively, describe progress made on the SuperB Project since the publication of the SuperB Conceptual Design Report in 2007 and the Proceedings of SuperB Workshop VI in Valencia in 2008.

SuperB Progress Report: Detector

International Nuclear Information System (INIS)

Grauges, E.; Donvito, G.; Spinoso, V.; Manghisoni, M.; Re, V.; Traversi, G.; Eigen, G.; Fehlker, D.; Helleve, L.; Cheng, C.; Chivukula, A.; Doll, D.; Echenard, B.; Hitlin, D.; Ongmongkolkul, P.; Porter, F.; Rakitin, A.; Thomas, M.; Zhu, R.; Tatishvili, G.; Andreassen, R.; Fabby, C.; Meadows, B.; Simpson, A.; Sokoloff, M.; Tomko, K.; Fella, A.; Andreotti, M.; Baldini, W.; Calabrese, R.; Carassiti, V.; Cibinetto, G.; Cotta Ramusino, A.; Gianoli, A.; Luppi, E.; Munerato, M.; Santoro, V.; Tomassetti, L.; Stoker, D.; Bezshyyko, O.; Dolinska, G.; Arnaud, N.; Beigbeder, C.; Bogard, F.; Breton, D.; Burmistrov, L.; Charlet, D.; Maalmi, J.; Perez Perez, L.; Puill, V.; Stocchi, A.; Tocut, V.; Wallon, S.; Wormser, G.; Brown, D.

2012-01-01

This report describes the present status of the detector design for SuperB. It is one of four separate progress reports that, taken collectively, describe progress made on the SuperB Project since the publication of the SuperB Conceptual Design Report in 2007 and the Proceedings of SuperB Workshop VI in Valencia in 2008.

SuperB Progress Reports Accelerator

CERN Document Server

Biagini, Maria Enrica; Boscolo, M; Buonomo, B; Demma, T; Drago, A; Esposito, M; Guiducci, S; Mazzitelli, G; Pellegrino, L; Preger, M A; Raimondi, P; Ricci, R; Rotundo, U; Sanelli, C; Serio, M; Stella, A; Tomassini, S; Zobov, M; Bertsche, K; Brachman, A; Cai, Y; Chao, A; Chesnut, R; Donald, M.H; Field, C; Fisher, A; Kharakh, D; Krasnykh, A; Moffeit, K; Nosochkov, Y; Pivi, M; Seeman, J; Sullivan, M.K; Weathersby, S; Weidemann, A; Weisend, J; Wienands, U; Wittmer, W; Woods, M; Yocky, G; Bogomiagkov, A; Koop, I; Levichev, E; Nikitin, S; Okunev, I; Piminov, P; Sinyatkin, S; Shatilov, D; Vobly, P; Bosi, F; Liuzzo, S; Paoloni, E; Bonis, J; Chehab, R; Le Meur, G; Lepercq, P; Letellier-Cohen, F; Mercier, B; Poirier, F; Prevost, C; Rimbault, C; Touze, F; Variola, A; Bolzon, B; Brunetti, L; Jeremie, A; Baylac, M; Bourrion, O; De Conto, J M; Gomez, Y; Meot, F; Monseu, N; Tourres, D; Vescovi, C; Chanci, A; Napoly, O; Barber, D P; Bettoni, S; Quatraro, D

2010-01-01

This report details the present status of the Accelerator design for the SuperB Project. It is one of four separate progress reports that, taken collectively, describe progress made on the SuperB Project since the publication of the SuperB Conceptual Design Report in 2007 and the Proceedings of SuperB Workshop VI in Valencia in 2008.

Annual progress report 1981

International Nuclear Information System (INIS)

1982-01-01

This annual progress report of the CEA Protection and Nuclear Safety Institut outlines a brief description of the progress made in each section of the Institut. Research activities of the Protection department include, radiation effects on man, radioecology and environment radioprotection techniques. Research activities of the Nuclear Safety department include, reactor safety analysis, fuel cycle facilities safety analysis, safety research programs. The third section deals with nuclear material security including security of facilities, security of nuclear material transport and monitoring of nuclear material management [fr

A survey on the progress with implementation of the radiography profession's career progression framework in UK radiotherapy centres

International Nuclear Information System (INIS)

James, Sarah; Beardmore, Charlotte; Dumbleton, Claire

2012-01-01

Aim: The purpose of the survey was to benchmark the progress with implementing the radiography profession's career progression framework within radiotherapy centres across the United Kingdom (UK). Methods: A survey questionnaire was constructed using the Survey Monkey™ tool to assess implementation of the career progression framework of the Society and College of Radiographers. Once constructed, an on line link to the survey questionnaire was emailed to all radiotherapy centre managers in the UK (N = 67) who were invited to provide one response per centre. The survey comprised twenty nine questions which were grouped into nine sections. Key results: The workforce profile indicates that increases in assistant, advanced and consultant level practitioners are required to meet National Radiotherapy Advisory Group recommendations with only a small number of centres having fully implemented the career progression framework. The overall vacancy level across the therapeutic radiography workforce was 4.6% at the time of the survey. Conclusions: and Recommendations: The survey has highlighted some progress with implementation of the career progression framework across the UK since its launch in 2000. However the current level of implementation demonstrated is disappointing considering it is a key recommendation within the NRAG Report 2007 with respect to England. It is recommended that all centres undertake a multi-professional workforce review to embed the career progression framework within their service in order to meet the workforce challenge associated with the required anticipated large growth in radiotherapy capacity.

Progress in physical chemistry

CERN Document Server

Hempelmann, Rolf

2008-01-01

Progress in Physical Chemistry is a collection of recent ""Review Articles"" published in the ""Zeitschrift für Physikalische Chemie"". The second volume of Progress in Physical Chemistry is a collection of thematically closely related minireview articles written by the members of the Collaborative Research Centre (SFB) 277 of the German Research Foundation (DFG). These articles are based on twelve years of intense coordinated research efforts. Central topics are the synthesis and the characterization of interface-dominated, i.e. nanostructured materials, mainly in the solid state but also as

1985. Annual progress report

International Nuclear Information System (INIS)

1986-01-01

This annual progress report of the CEA Protection and Nuclear Safety Institut outlines a description of the progress made in each sections of the Institut Research activities of the different departments include: reactor safety analysis, fuel cycle facilities analysis; and associated safety research programs (criticality, sites, transport ...), radioecology and environmental radioprotection techniques; data acquisition on radioactive waste storage sites; radiation effects on man, studies on radioprotection techniques; nuclear material security including security of facilities, security of nuclear material transport, and monitoring of nuclear material management; nuclear facility decommissioning; and finally the public information [fr

[Charles Darwin and the problem of evolutionary progress].

Science.gov (United States)

Iordanskiĭ, N N

2010-01-01

According to Ch. Darwin's evolutionary theory, evolutionary progress (interpreted as morpho-physiological progress or arogenesis in recent terminology) is one of logical results of natural selection. At the same time, natural selection does not hold any factors especially promoting evolutionary progress. Darwin emphasized that the pattern of evolutionary changes depends on organism nature more than on the pattern of environment changes. Arogenesis specificity is determined by organization of rigorous biological systems - integral organisms. Onward progressive development is determined by fundamental features of living organisms: metabolism and homeostasis. The concept of social Darwinism differs fundamentally from Darwin's ideas about the most important role of social instincts in progress of mankind. Competition and selection play secondary role in socio-cultural progress of human society.

Progress report 1985

International Nuclear Information System (INIS)

1986-01-01

This progress report of the nuclear physics institute includes five basic subjects: theoretical physics, high energy and intermediate energy physics, nuclear physics, combined research physics and instrumentation (microelectronics, imaging, multidetectors, scintillators,...) [fr

Detergent-induced aggregation of an amyloidogenic intrinsically ...

Indian Academy of Sciences (India)

Shruti Arya

2017-11-02

Nov 2, 2017 ... the effect of a well-known anionic lipid mimetic, sodium dodecyl sulfate (SDS), on the aggregation ... for the fabrication of nano-structures for a wide variety ...... M 2014 Classification of intrinsically disordered regions.

Targeting ECM Disrupts Cancer Progression

DEFF Research Database (Denmark)

Venning, Freja A; Wullkopf, Lena; Erler, Janine T

2015-01-01

, the extracellular matrix (ECM). Many ECM proteins are significantly deregulated during the progression of cancer, causing both biochemical and biomechanical changes that together promote the metastatic cascade. In this review, the influence of several ECM proteins on these multiple steps of cancer spread...... is summarized. In addition, we highlight the promising (pre-)clinical data showing benefits of targeting these ECM macromolecules to prevent cancer progression....

THE EFFECTS OF SINGLE LEG HOP PROGRESSION AND DOUBLE LEGS HOP PROGRESSION EXERCISE TO INCREASE SPEED AND EXPLOSIVE POWER OF LEG MUSCLE

Directory of Open Access Journals (Sweden)

Nining W. Kusnanik

2015-05-01

Full Text Available The main purpose of this study was to determine the effect of single leg hop progression and double legs hop progression exercise to increase speed and explosive power of leg muscles. Plyometric is one of the training methods that can increase explosive power. There are many models of plyometric training including single leg hop progression and double leg hop progression. This research was experimental using match subject design techniques. The subjects of this study were 39 students who joined basketball school club. There were 3 groups in this study: Group 1 were 13 students who given sin¬gle leg hop progression exercise, Group 2 were 13 students who given double legs hop progression exercise, Group 3 were 13 students who given conventional exercise. The data was collected during pre test and post test by testing 30m speed running and vertical jump. The data was analyzed using Analysis of Varians (Anova. It was found that there were significantly increased on speed and explosive power of leg muscles of Group 1 and Group 2. It can be stated that single leg hop progression exercise was more effective than double leg hop progression exercise. The recent findings supported the hypothesis that single leg hop progression and double legs hop progression exercise can increase speed and explosive power of leg muscles. These finding were supported by some previous studies (Singh, et al, 2011; Shallaby, H.K., 2010. The single leg hop progression is more effective than double legs hop progression. This finding was consistent with some previous evidences (McCurdy, et al, 2005; Makaruk et al, 2011.

Effects of Canon chord progression on brain activity and motivation are dependent on subjective feelings, not the chord progression per se

Directory of Open Access Journals (Sweden)

Kayashima Y

2017-06-01

Full Text Available Yoshinori Kayashima,1,2,* Kazuhiko Yamamuro,1,* Manabu Makinodan,1 Yoko Nakanishi,1 Akio Wanaka,2 Toshifumi Kishimoto1 1Department of Psychiatry, 2Department of Anatomy and Neuroscience, Nara Medical University School of Medicine, Kashihara, Japan *These authors contributed equally to this work Abstract: A number of studies have indicated that relaxing and pleasant melodies are useful for the treatment of patients with psychiatric disorders, including schizophrenia, depression, and dementia. However, few studies have investigated what constitutive elements of the music had an effect on brain activity. As Canon chord progression is one of critical elements for pleasant melodies, we sought to examine the effects of Canon chord progression and pitch-shifted Canon chord progression on brain activity using performance on the auditory oddball task during event-related potentials (ERPs in 30 healthy subjects. Unexpectedly, we found no differences in ERP components between subjects listening to Canon chord progression (n=15 or pitch-shifted Canon chord progression (n=15. Next, we divided participants into two groups: those who found the melody pleasant (n=17 and those who did not (n=13, for both Canon chord progression and pitch-shifted Canon chord progression. The average of P300 amplitude was higher at Fz in subjects found the music pleasant versus those finding it unpleasant. Moreover, subjects who found it pleasant exhibited higher motivation scores than those who felt it was unpleasant, whereas listening to Canon chord progression did not matter. These findings suggest that the effects of Canon chord progression on brain activity and motivation depend on subjective feelings, not the chord progression per se. Keywords: music, Canon chord progression, motivation, event-related potential, subjective feelings 

Epigenetic Regulation in Prostate Cancer Progression.

Science.gov (United States)

Ruggero, Katia; Farran-Matas, Sonia; Martinez-Tebar, Adrian; Aytes, Alvaro

2018-01-01

An important number of newly identified molecular alterations in prostate cancer affect gene encoding master regulators of chromatin biology epigenetic regulation. This review will provide an updated view of the key epigenetic mechanisms underlying prostate cancer progression, therapy resistance, and potential actionable mechanisms and biomarkers. Key players in chromatin biology and epigenetic master regulators has been recently described to be crucially altered in metastatic CRPC and tumors that progress to AR independency. As such, epigenetic dysregulation represents a driving mechanism in the reprograming of prostate cancer cells as they lose AR-imposed identity. Chromatin integrity and accessibility for transcriptional regulation are key features altered in cancer progression, and particularly relevant in nuclear hormone receptor-driven tumors like prostate cancer. Understanding how chromatin remodeling dictates prostate development and how its deregulation contributes to prostate cancer onset and progression may improve risk stratification and treatment selection for prostate cancer patients.

Spinal Cord Stimulation Alters Protein Levels in the Cerebrospinal Fluid of Neuropathic Pain Patients: A Proteomic Mass Spectrometric Analysis.

Science.gov (United States)

Lind, Anne-Li; Emami Khoonsari, Payam; Sjödin, Marcus; Katila, Lenka; Wetterhall, Magnus; Gordh, Torsten; Kultima, Kim

2016-08-01

Electrical neuromodulation by spinal cord stimulation (SCS) is a well-established method for treatment of neuropathic pain. However, the mechanism behind the pain relieving effect in patients remains largely unknown. In this study, we target the human cerebrospinal fluid (CSF) proteome, a little investigated aspect of SCS mechanism of action. Two different proteomic mass spectrometry protocols were used to analyze the CSF of 14 SCS responsive neuropathic pain patients. Each patient acted as his or her own control and protein content was compared when the stimulator was turned off for 48 hours, and after the stimulator had been used as normal for three weeks. Eighty-six proteins were statistically significantly altered in the CSF of neuropathic pain patients using SCS, when comparing the stimulator off condition to the stimulator on condition. The top 12 of the altered proteins are involved in neuroprotection (clusterin, gelsolin, mimecan, angiotensinogen, secretogranin-1, amyloid beta A4 protein), synaptic plasticity/learning/memory (gelsolin, apolipoprotein C1, apolipoprotein E, contactin-1, neural cell adhesion molecule L1-like protein), nociceptive signaling (neurosecretory protein VGF), and immune regulation (dickkopf-related protein 3). Previously unknown effects of SCS on levels of proteins involved in neuroprotection, nociceptive signaling, immune regulation, and synaptic plasticity are demonstrated. These findings, in the CSF of neuropathic pain patients, expand the picture of SCS effects on the neurochemical environment of the human spinal cord. An improved understanding of SCS mechanism may lead to new tracks of investigation and improved treatment strategies for neuropathic pain. © 2016 International Neuromodulation Society.

Aggregation properties of a short peptide that mediates amyloid fibril ...

Indian Academy of Sciences (India)

Short peptides have been identified from amyloidogenic proteins that form amyloid fibrils in isolation. The ... proteins. These peptide fibrils have the conformational features of β-structure that .... water and immediately deposited on freshly cleaved surface of mica .... with the peptide via electrostatic interactions. NaCl would.

Progress report 1979

International Nuclear Information System (INIS)

1979-01-01

Progress report on the meetings and working groups of DAF in 1979, e.g. engineering and industry, public and press, law and administration, business and industry, international cooperation in Europe and with the USA. (GL) [de

Efficient progressive taxes and education subsidies

NARCIS (Netherlands)

van Ewijk, C.; Tang, P.J.G.

2001-01-01

Progressive income taxes moderate wage demands by trade unions and thereby reduce unemployment, but alsothey reduce incentives to acquire skills and lower productivity of workers. The optimal response of the governmentto this dilemma is to choose a system of progressive taxes and to (partly)

Theoretical progress at CNDC theory group

International Nuclear Information System (INIS)

Lu Zhongdao

1993-01-01

In 1992, CNDC (Chinese Nuclear Data Center) theory group has made progress in model study, code making and data calculations for low energy nuclear reaction, intermediate and high energy nuclear reaction. It has also made progress in parameter library establishment. The brief explanations are presented

LINGO-1 promotes lysosomal degradation of amyloid-β protein precursor

Directory of Open Access Journals (Sweden)

Rian de Laat

2015-03-01

Full Text Available Sequential proteolytic cleavages of amyloid-β protein precursor (AβPP by β-secretase and γ-secretase generate amyloid β (Aβ peptides, which are thought to contribute to Alzheimer's disease (AD. Much of this processing occurs in endosomes following endocytosis of AβPP from the plasma membrane. However, this pathogenic mode of processing AβPP may occur in competition with lysosomal degradation of AβPP, a common fate of membrane proteins trafficking through the endosomal system. Following up on published reports that LINGO-1 binds and promotes the amyloidogenic processing of AβPP we have examined the consequences of LINGO-1/AβPP interactions. We report that LINGO-1 and its paralogs, LINGO-2 and LINGO-3, decrease processing of AβPP in the amyloidogenic pathway by promoting lysosomal degradation of AβPP. We also report that LINGO-1 levels are reduced in AD brain, representing a possible pathogenic mechanism stimulating the generation of Aβ peptides in AD.

Amyloidogenesis abolished by proline substitutions but enhanced by lipid binding.

Directory of Open Access Journals (Sweden)

Ping Jiang

2009-04-01

Full Text Available The influence of lipid molecules on the aggregation of a highly amyloidogenic segment of human islet amyloid polypeptide, hIAPP20-29, and the corresponding sequence from rat has been studied by all-atom replica exchange molecular dynamics (REMD simulations with explicit solvent model. hIAPP20-29 fragments aggregate into partially ordered beta-sheet oligomers and then undergo large conformational reorganization and convert into parallel/antiparallel beta-sheet oligomers in mixed in-register and out-of-register patterns. The hydrophobic interaction between lipid tails and residues at positions 23-25 is found to stabilize the ordered beta-sheet structure, indicating a catalysis role of lipid molecules in hIAPP20-29 self-assembly. The rat IAPP variants with three proline residues maintain unstructured micelle-like oligomers, which is consistent with non-amyloidogenic behavior observed in experimental studies. Our study provides the atomic resolution descriptions of the catalytic function of lipid molecules on the aggregation of IAPP peptides.

Storming the Citadel: The Fundamental Revolution Against Progressive Education.

Science.gov (United States)

Vetterli, Richard

The first four chapters ("Progressive Education,""The Impact of Progressive Education,""The Remedies: Focusing on the Wrong Problems," and "Progressive Education Challenged") examine the deleterious effect that progressive education has had on student achievement and on society as a whole. The last five…

Rapid progression of gliomatosis cerebri to secondary glioblastoma, factors that affects the progression rate: A case report

Energy Technology Data Exchange (ETDEWEB)

Kim, Hee Kyung; Yu, In Kyu; Kim, Seung Min; Kim, Joo Heon; Lee, Seung Hoon; Lee, Seung Yeon [Eulji University Hospital, Daejeon (Korea, Republic of)

2017-03-15

Glioblastomas may develop de novo or through progression from low-grade or anaplastic astrocytomas. The term 'primary glioblastoma' refers to a glioblastoma that lacks a precursor lesion and has a clinical history of less than three months. On the other hand, the term 'secondary glioblastoma' indicates that the glioblastoma has progressed from a low-grade tumor after a long latency period and often manifests in younger patients. These subtypes of glioblastoma develop via different genetic pathways, and they differ in prognosis and response to therapy. Thus, differential diagnosis of these subtypes and prediction of the factors that affect the progression from low-grade diffuse astrocytoma to secondary glioblastoma would be clinically very important. We present a rare case of secondary glioblastoma, which developed only three months after the follow up imaging evaluations, with a history of low grade glioma, and present the factors that cause rapid progression.

Progress: Its Glories and Pitfalls.

Science.gov (United States)

Callahan, Daniel

2018-03-01

Steven Pinker, a cognitive psychologist and linguist at Harvard and a savant of big ideas, is one of the latest to take on the idea of progress. He does it under the aegis of "enlightenment," which comes down to a kind of holy trinity of reason, science, and humanism. His new book, Enlightenment Now: The Case for Reason, Science, Humanism, and Progress, is ambitious and cantankerous and heady with hope. On the whole, Pinker makes a good case for the benefits of progress, but with an overdose of feel-good prose. His greatest failure comes in exaggerating the threats to science and in avoiding some problems altogether. He ignores its complexity, its shadows, its creation of new problems raised by its solutions to old ones. Pinker has a particular animus against bioethics, and he misses what has been, I would argue, at the heart of bioethics from its beginning fifty or so years ago. Bioethics was prompted by a new class of medical dilemmas that require a difficult balancing of harms and benefits. Most of them are still with us, and most of them are the result of the progress of postwar medical research and fast-changing clinical practices. © 2018 The Hastings Center.

Content Progressive Coding of Limited Bits/pixel Images

DEFF Research Database (Denmark)

Jensen, Ole Riis; Forchhammer, Søren

1999-01-01

A new lossless context based method for content progressive coding of limited bits/pixel images is proposed. Progressive coding is achieved by separating the image into contelnt layers. Digital maps are compressed up to 3 times better than GIF.......A new lossless context based method for content progressive coding of limited bits/pixel images is proposed. Progressive coding is achieved by separating the image into contelnt layers. Digital maps are compressed up to 3 times better than GIF....

Tracking Clean Energy Progress 2013

Energy Technology Data Exchange (ETDEWEB)

NONE

2013-06-01

Tracking Clean Energy Progress 2013 (TCEP 2013) examines progress in the development and deployment of key clean energy technologies. Each technology and sector is tracked against interim 2020 targets in the IEA Energy Technology Perspectives 2012 2°C scenario, which lays out pathways to a sustainable energy system in 2050. Stark message emerge: progress has not been fast enough; large market failures are preventing clean energy solutions from being taken up; considerable energy efficiency remains untapped; policies need to better address the energy system as a whole; and energy-related research, development and demonstration need to accelerate. Alongside these grim conclusions there is positive news. In 2012, hybrid-electric vehicle sales passed the 1 million mark. Solar photovoltaic systems were being installed at a record pace. The costs of most clean energy technologies fell more rapidly than anticipated.

Relapsing and Progressive Tumefactive Demyelinating Form of Central Nervous System Involvement in a Patient with Progressive Systemic Sclerosis

International Nuclear Information System (INIS)

Kim, Ho Kyun; Lee, Hui Joong

2013-01-01

White matter hyper intensities (WMHI) on MRI are not rare in patients with progressive systemic sclerosis (PSS). In this presentation, WMHI were developed in both middle cerebellar peduncles and temporal white matter in a patient with PSS, and regressed after medication of high dose steroid. However, new lesions were developed in the subcortices of both precentral gyri, and progressed rapidly to tumefactive hyperintensity on MRI. We report an unusual relapsing and progressive tumefactive demyelinating form of central nervous system involvement in PSS.

Annual Progress report - General Task

International Nuclear Information System (INIS)

Wesnousky, S.G.

1993-01-01

This report provides a summary of progress for the project open-quotes Evaluation of the Geologic Relations and Seismotectonic Stability of the Yucca Mountain Area, Nevada Nuclear Waste Site Investigation (NNWSI).close quotes A similar report was previously provided for the period of 1 October 1991 to 30 September 1992. The report initially covers the activities of the General Task and is followed by sections that describe the progress of the other ongoing tasks

Progressive technologies in furniture design

OpenAIRE

Šebková, Martina

2014-01-01

Šebková, M. Progressive technologies in furniture design. Diploma thesis, Brno, Mendel University in Brno, 2014 Diploma thesis 'Progressive technologies in furniture design' is focused on the use of modern technologies in furniture production. The theoretical part explains the basic terms, technology and material options. It focuses mainly on the production of 3D printed furniture and possibilities of virtual testing, measurements, scanning and rapid prototyping. Practical part of diploma the...

Estrogens and progression of diabetic kidney damage.

Science.gov (United States)

Doublier, Sophie; Lupia, Enrico; Catanuto, Paola; Elliot, Sharon J

2011-01-01

It is generally accepted that estrogens affect and modulate the development and progression of chronic kidney diseases (CKD) not related to diabetes. Clinical studies have indeed demonstrated that the severity and rate of progression of renal damage tends to be greater among men, compared with women. Experimental studies also support the notion that female sex is protective and male sex permissive, for the development of CKD in non-diabetics, through the opposing actions of estrogens and testosterone. However, when we consider diabetes-induced kidney damage, in the setting of either type 1 or type 2 diabetes, the contribution of gender to the progression of renal disease is somewhat uncertain. Previous studies on the effects of estrogens in the pathogenesis of progressive kidney damage have primarily focused on mesangial cells. More recently, data on the effects of estrogens on podocytes, the cell type whose role may include initiation of progressive diabetic renal disease, became available. The aim of this review will be to summarize the main clinical and experimental data on the effects of estrogens on the progression of diabetes-induced kidney injury. In particular, we will highlight the possible biological effects of estrogens on podocytes, especially considering those critical for the pathogenesis of diabetic kidney damage.

Healthy brain connectivity predicts atrophy progression in non-fluent variant of primary progressive aphasia.

Science.gov (United States)

Mandelli, Maria Luisa; Vilaplana, Eduard; Brown, Jesse A; Hubbard, H Isabel; Binney, Richard J; Attygalle, Suneth; Santos-Santos, Miguel A; Miller, Zachary A; Pakvasa, Mikhail; Henry, Maya L; Rosen, Howard J; Henry, Roland G; Rabinovici, Gil D; Miller, Bruce L; Seeley, William W; Gorno-Tempini, Maria Luisa

2016-10-01

Neurodegeneration has been hypothesized to follow predetermined large-scale networks through the trans-synaptic spread of toxic proteins from a syndrome-specific epicentre. To date, no longitudinal neuroimaging study has tested this hypothesis in vivo in frontotemporal dementia spectrum disorders. The aim of this study was to demonstrate that longitudinal progression of atrophy in non-fluent/agrammatic variant primary progressive aphasia spreads over time from a syndrome-specific epicentre to additional regions, based on their connectivity to the epicentre in healthy control subjects. The syndrome-specific epicentre of the non-fluent/agrammatic variant of primary progressive aphasia was derived in a group of 10 mildly affected patients (clinical dementia rating equal to 0) using voxel-based morphometry. From this region, the inferior frontal gyrus (pars opercularis), we derived functional and structural connectivity maps in healthy controls (n = 30) using functional magnetic resonance imaging at rest and diffusion-weighted imaging tractography. Graph theory analysis was applied to derive functional network features. Atrophy progression was calculated using voxel-based morphometry longitudinal analysis on 34 non-fluent/agrammatic patients. Correlation analyses were performed to compare volume changes in patients with connectivity measures of the healthy functional and structural speech/language network. The default mode network was used as a control network. From the epicentre, the healthy functional connectivity network included the left supplementary motor area and the prefrontal, inferior parietal and temporal regions, which were connected through the aslant, superior longitudinal and arcuate fasciculi. Longitudinal grey and white matter changes were found in the left language-related regions and in the right inferior frontal gyrus. Functional connectivity strength in the healthy speech/language network, but not in the default network, correlated with

Tumor heterogeneity and progression: conceptual foundations for modeling.

Science.gov (United States)

Greller, L D; Tobin, F L; Poste, G

1996-01-01

A conceptual foundation for modeling tumor progression, growth, and heterogeneity is presented. The purpose of such models is to aid understanding, test ideas, formulate experiments, and to model cancer 'in machina' to address the dynamic features of tumor cell heterogeneity, progression, and growth. The descriptive capabilities of such an approach provides a consistent language for qualitatively reasoning about tumor behavior. This approach provides a schema for building conceptual models that combine three key phenomenological driving elements: growth, progression, and genetic instability. The growth element encompasses processes contributing to changes in tumor bulk and is distinct from progression per se. The progression element subsumes a broad collection of processes underlying phenotypic progression. The genetics elements represents heritable changes which potentially affect tumor character and behavior. Models, conceptual and mathematical, can be built for different tumor situations by drawing upon the interaction of these three distinct driving elements. These models can be used as tools to explore a diversity of hypotheses concerning dynamic changes in cellular populations during tumor progression, including the generation of intratumor heterogeneity. Such models can also serve to guide experimentation and to gain insight into dynamic aspects of complex tumor behavior.

Female Progress and Discrimination. An Economic Perspective

OpenAIRE

Sandra E. Black

2005-01-01

In the last 20 years, women’s economic progress has been staggering; this progress is particularly startling given that this has also been a period of marked increases in income inequality overall, declining relative wages of blacks, and declining real wages of low-skilled workers. Recent work has proposed a number of possible explanations for the progress of women, including changing social norms (in part facilitated by technological/pharmaceutical advances), increasing skill acquisition, ch...

Progressive Web applications

CERN Multimedia

CERN. Geneva

2017-01-01

Progressive Web Applications are native-like applications running inside of a browser context. In my presentation I would like describe their characteristics, benchmarks and building process using a quick and simple case study example with focus on Service Workers api.

23 CFR 140.609 - Progress and final vouchers.

Science.gov (United States)

2010-04-01

... 23 Highways 1 2010-04-01 2010-04-01 false Progress and final vouchers. 140.609 Section 140.609 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION PAYMENT PROCEDURES REIMBURSEMENT Reimbursement for Bond Issue Projects § 140.609 Progress and final vouchers. (a) Progress vouchers may be...

Learning Progressions as Tools for Assessment and Learning

Science.gov (United States)

Shepard, Lorrie A.

2018-01-01

This article addresses the teaching and learning side of the learning progressions literature, calling out for measurement specialists the knowledge most needed when collaborating with subject-matter experts in the development of learning progressions. Learning progressions are one of the strongest instantiations of principles from "Knowing…

A Learning Progression for Elementary Students' Functional Thinking

Science.gov (United States)

Stephens, Ana C.; Fonger, Nicole; Strachota, Susanne; Isler, Isil; Blanton, Maria; Knuth, Eric; Murphy Gardiner, Angela

2017-01-01

In this article we advance characterizations of and supports for elementary students' progress in generalizing and representing functional relationships as part of a comprehensive approach to early algebra. Our learning progressions approach to early algebra research involves the coordination of a curricular framework and progression, an…

38 CFR 21.7653 - Progress, conduct, and attendance.

Science.gov (United States)

2010-07-01

... on which the school official who is responsible for determining whether a student is making progress...) Satisfactory pursuit of program. In order to receive educational assistance for pursuit of a program of education, a reservist must maintain satisfactory progress. Progress is unsatisfactory if the reservist does...

Evaluating progressive-rendering algorithms in appearance design tasks.

Science.gov (United States)

Jiawei Ou; Karlik, Ondrej; Křivánek, Jaroslav; Pellacini, Fabio

2013-01-01

Progressive rendering is becoming a popular alternative to precomputational approaches to appearance design. However, progressive algorithms create images exhibiting visual artifacts at early stages. A user study investigated these artifacts' effects on user performance in appearance design tasks. Novice and expert subjects performed lighting and material editing tasks with four algorithms: random path tracing, quasirandom path tracing, progressive photon mapping, and virtual-point-light rendering. Both the novices and experts strongly preferred path tracing to progressive photon mapping and virtual-point-light rendering. None of the participants preferred random path tracing to quasirandom path tracing or vice versa; the same situation held between progressive photon mapping and virtual-point-light rendering. The user workflow didn’t differ significantly with the four algorithms. The Web Extras include a video showing how four progressive-rendering algorithms converged (at http://youtu.be/ck-Gevl1e9s), the source code used, and other supplementary materials.

PSI-Center Final Progress Report

Energy Technology Data Exchange (ETDEWEB)

Jarboe, Thomas R. [Univ. of Washington, Seattle, WA (United States); Shumlak, Uri [Univ. of Washington, Seattle, WA (United States); Sovinec, Carl [Univ. of Washington, Seattle, WA (United States); Hansen, Chris [Univ. of Washington, Seattle, WA (United States); Ji, Jeong-Young [Utah State Univ., Logan, UT (United States); Nelson, Brian [Univ. of Wisconsin, Madison, WI (United States)

2017-04-20

This is the Final Progress Report of the Plasma Science and Innovation Center (PSI-Center) covering March 2014 through February 2017. The Center has accomplished a great deal during this period. The PSI-Center is organized into four groups: Edge and Dynamic Neutrals; Transport and Kinetic Effects; Equilibrium, Stability, and Kinetic Effects in 3D Topologies; and Interface for Validation. Each group has made good progress and the results from each group are given in detail.

Rapidly Progressive Quadriplegia and Encephalopathy.

Science.gov (United States)

Wynn, DonRaphael; McCorquodale, Donald; Peters, Angela; Juster-Switlyk, Kelsey; Smith, Gordon; Ansari, Safdar

2016-11-01

A woman aged 77 years was transferred to our neurocritical care unit for evaluation and treatment of rapidly progressive motor weakness and encephalopathy. Examination revealed an ability to follow simple commands only and abnormal movements, including myoclonus, tongue and orofacial dyskinesias, and opsoclonus. Imaging study findings were initially unremarkable, but when repeated, they demonstrated enhancement of the cauda equina nerve roots, trigeminal nerve, and pachymeninges. Cerebrospinal fluid examination revealed mildly elevated white blood cell count and protein levels. Serial electrodiagnostic testing demonstrated a rapidly progressive diffuse sensory motor axonopathy, and electroencephalogram findings progressed from generalized slowing to bilateral periodic lateralized epileptiform discharges. Critical details of her recent history prompted a diagnostic biopsy. Over time, the patient became completely unresponsive with no further abnormal movements and ultimately died. The differential diagnosis, pathological findings, and diagnosis are discussed with a brief review of a well-known yet rare diagnosis.

World progress toward fusion energy

International Nuclear Information System (INIS)

Davies, N.A.

1989-01-01

The author discusses international progress in fusion research during the last three years. Much of the technical progress has been achieved through international collaboration in magnetic fusion research. This progress has stimulated political interest in a multinational effort, aimed at designing and possibly constructing the world's first experimental fusion reactor. This interest was reflected in recent summit-level discussions involving President Mitterand, General Secretary Gorbachev, and President Reagan. Most recently, the European Community (EC), Japan, the United States, and the U.S.S.R. have decided to begin serious preparation for taking the next step toward practical fusion energy. These parties have agreed to begin the design and supporting R and D for an International Thermonuclear Experimental Reactor (ITER) under the auspices of the International Atomic Energy Agency (IAEA). The initiation of this international program to prepare for a fusion test reactor is discussed

Description of load progression and pain response during progressive resistance training early after total hip arthroplasty

DEFF Research Database (Denmark)

Mikkelsen, Lone R; Petersen, Annemette K; Mechlenburg, Inger

2016-01-01

events during the initial four weeks of training. RESULTS: The majority of patients experienced only moderate hip pain during exercise (range in median across exercises and sessions: 5-35 mm Visual Analog Scale) and mild pain at rest (median: 1-18 mm Visual Analog Scale), both of which decreased over...... time ( p training load (67%-166 % across exercises, p training sessions, short term pain response (an increase >20 mm Visual Analog Scale) occurred in 13 patients in 24 training sessions. CONCLUSION: Progressive resistance......OBJECTIVE: To describe a progressive resistance training intervention implemented shortly after total hip arthroplasty, including a detailed description of load progression, pain response and adverse events to the training. DESIGN: Secondary analyses of data from the intervention group...

Cross-seeding of prions by aggregated α-synuclein leads to transmissible spongiform encephalopathy.

Directory of Open Access Journals (Sweden)

Elizaveta Katorcha

2017-08-01

Full Text Available Aggregation of misfolded proteins or peptides is a common feature of neurodegenerative diseases including Alzheimer's, Parkinson's, Huntington's, prion and other diseases. Recent years have witnessed a growing number of reports of overlap in neuropathological features that were once thought to be unique to only one neurodegenerative disorder. However, the origin for the overlap remains unclear. One possibility is that diseases with mixed brain pathologies might arise from cross-seeding of one amyloidogenic protein by aggregated states of unrelated proteins. In the current study we examined whether prion replication can be induced by cross-seeding by α-synuclein or Aβ peptide. We found that α-synuclein aggregates formed in cultured cells or in vitro display cross-seeding activity and trigger misfolding of the prion protein (PrPC in serial Protein Misfolding Cyclic Amplification reactions, producing self-replicating PrP states characterized by a short C-terminal proteinase K (PK-resistant region referred to as PrPres. Non-fibrillar α-synuclein or fibrillar Aβ failed to cross-seed misfolding of PrPC. Remarkably, PrPres triggered by aggregated α-synuclein in vitro propagated in animals and, upon serial transmission, produced PrPSc and clinical prion disease characterized by spongiosis and astrocytic gliosis. The current study demonstrates that aggregated α-synuclein is potent in cross-seeding of prion protein misfolding and aggregation in vitro, producing self-replicating states that can lead to transmissible prion diseases upon serial passaging in wild type animals. In summary, the current work documents direct cross-seeding between unrelated amyloidogenic proteins associated with different neurodegenerative diseases. This study suggests that early interaction between unrelated amyloidogenic proteins might underlie the etiology of mixed neurodegenerative proteinopathies.

Internationalisering og progression

DEFF Research Database (Denmark)

Wilken, Lisanne; Tange, Hanne

2014-01-01

means that programs can attract students from outside Denmark, and these students often come from different academic backgrounds. To investigate how these changes are affecting the way professors who teach on interdisciplinary international masters programs conceive student progress, we carried out semi...

Progress report 1979

International Nuclear Information System (INIS)

1980-12-01

This progress report deals with service oriented work performed at the AAEC Research Establishment in the twelve month period ending September 30, 1979. Services provided by the Engineering Services Division, the Safety Department, Site Information Services Department and Commercial Applications are described

Factors of progress in reading literacy test

Directory of Open Access Journals (Sweden)

Jovanović Vitomir

2011-01-01

Full Text Available The main goal of this study was to identify the factors which are most associated with the progress in reading literacy assessed in the PISA survey. In the preliminary sample, students from ten schools (N=235 were retested two years after the 2009 PISA original study. There were measured intrinsic and extrinsic motivation, school self-efficacy, epistemological beliefs, metacognitive strategies, socio-economic status, enjoyment and preference for reading and motivation and self-regulation. The examined factors explain 27% of the variance in reading literacy progress. Factors that contribute most to this progress are school self-efficacy, proper use of metacognitive strategies and low extrinsic motivation. Socio-economic status explained a negligible amount of variance, while some effect of type of school on progress in reading literacy (η2=7% was observed. Achievement in reading literacy is correlated with school marks. Students who attend secondary schools are more likely to make progress in reading literacy than those who attend vocational schools. An attempt was made to formulate the implications for education policy based on this research.

The neural basis of monitoring goal progress

Directory of Open Access Journals (Sweden)

Yael eBenn

2014-09-01

Full Text Available The neural basis of progress monitoring has received relatively little attention compared to other sub-processes that are involved in goal directed behavior such as motor control and response inhibition. Studies of error-monitoring have identified the dorsal anterior cingulate cortex (dACC as a structure that is sensitive to conflict detection, and triggers corrective action. However, monitoring goal progress involves monitoring correct as well as erroneous events over a period of time. In the present research, 20 healthy participants underwent fMRI while playing a game that involved monitoring progress towards either a numerical or a visuo-spatial target. The findings confirmed the role of the dACC in detecting situations in which the current state may conflict with the desired state, but also revealed activations in the frontal and parietal regions, pointing to the involvement of processes such as attention and working memory in monitoring progress over time. In addition, activation of the cuneus was associated with monitoring progress towards a specific target presented in the visual modality. This is the first time that activation in this region has been linked to higher-order processing of goal-relevant information, rather than low-level anticipation of visual stimuli. Taken together, these findings identify the neural substrates involved in monitoring progress over time, and how these extend beyond activations observed in conflict and error monitoring.

Measuring and reporting on decommissioning progress

International Nuclear Information System (INIS)

Lange, B.A.

2006-01-01

One of the challenges facing AECL, as well as other organizations charged with the responsibility of decommissioning nuclear facilities, is the means by which to measure and report on decommissioning progress to various audiences which, in some cases, may only have a peripheral knowledge or understanding of the complexities associated with the decommissioning process. The reporting and measurement of decommissioning progress is important for a number of reasons, i.e., It provides a vehicle by which to effectively communicate the nature of the decommissioning process; It ensures that stakeholders and shareholders are provided with a transparent and understandable means for assessing value for money; It provides a means by which to integrate the planning, measurement, and operational aspects of decommissioning One underlying reason behind the challenge of reporting decommissioning progress lies in the fact that decommissioning programs are generally executed over periods of time that far exceed those generally associated with typical design and build projects. For example, a decommissioning program could take decades to complete in which case progress on the order of a few percent in any one year might be typical. However, such progress may appear low compared to that seen with more typical projects that can be completed in a matter of years. As a consequence, AECL undertook to develop a system by which to measure decommissioning progress in a straightforward, meaningful, and understandable fashion. The system is not rigorously objective, and there are subjective aspects that are necessitated by the need to keep the system readily understandable. It is also important to note that while the system is simple in concept, there is, nonetheless, significant effort involved in generating and updating the parameters used as input, and in the actual calculations. (author)

Primary progressive multiple sclerosis in the Polish population

Directory of Open Access Journals (Sweden)

Waldemar Brola

2017-03-01

Full Text Available Objectives: The aim of the study was the epidemiological analysis and evaluation of selected clinical and sociodemographic factors in Polish patients with primary progressive multiple sclerosis. Methods: The study included patients from 7 provinces in central and eastern Poland registered in the Registry of Patients with Multiple Sclerosis on 31 December 2016. The incidence of various forms of the disease was compared, and clinical, demographic and social disparities between relapsing-remitting and primary progressive multiple sclerosis were analysed. Results: Of 3,199 registered patients, 2,188 persons (66.2% had the relapsing-remitting form of multiple sclerosis, 774 (24.2% had the secondary progressive type and 307 (9.6% suffered from primary progressive disease. The first symptoms of primary progressive multiple sclerosis appeared almost 10 years later than in patients with the relapsing-remitting type (39.2 ± 11.4 vs. 29.8 ± 9.8. The period from the first symptoms to diagnosis was more than twice as long in patients with primary progressive multiple sclerosis (5.8 ± 3.4 as in those with relapsing-remitting disease (2.4 ± 1.6. The average degree of disability in the Expanded Disability Status Scale was similar and amounted to 3.2 ± 2.1 for relapsing-remitting and 3.6 ± 2.4 for primary progressive multiple sclerosis. The relapsing-remitting form was observed more often in women (2.4:1, and the primary progressive form appeared with equal frequency in both sexes (1:1. Disease-modifying treatment was received by 34% of patients with relapsing-remitting and in only 1.9% of patients with primary progressive multiple sclerosis. Conclusions: The primary progressive form affects approximately 10% of Polish patients with multiple sclerosis. The first symptoms appear at about 40 years of age with equal frequency in both sexes, and its diagnosis takes more than twice as much time as in the case of relapsing-remitting multiple

Drug-induced progressive multifocal leukoencephalopathy

DEFF Research Database (Denmark)

Vermeer, N S; Straus, S M J M; Mantel-Teeuwisse, A K

2015-01-01

Progressive multifocal leukoencephalopathy (PML) has been identified as a serious adverse drug reaction (ADR) of several immunomodulatory biologicals. In this study, we contrasted the reporting patterns of PML for two biologicals for which the risk was identified at different points in their life......Progressive multifocal leukoencephalopathy (PML) has been identified as a serious adverse drug reaction (ADR) of several immunomodulatory biologicals. In this study, we contrasted the reporting patterns of PML for two biologicals for which the risk was identified at different points...

Chronic progressive lymphoedema in draught horses.

Science.gov (United States)

de Keyser, K; Janssens, S; Buys, N

2015-05-01

The objective of this review was to summarise and evaluate the current state of knowledge about chronic progressive lymphoedema in draught horses. Clinical signs of this multifactorial disorder are mainly restricted to the lower limbs, comprising progressively deteriorating skin, swelling and deformation. Although typical lesions were first reported at the beginning of the 20th century, chronic progressive lymphoedema was recognised as a specific syndrome only in 2003, and since then research has driven forward. Despite the high prevalence in some breeds and the serious economic impact, the pathogenesis is not fully understood, and the available treatment options remain symptomatic and noncurative. There is a need to improve diagnostic techniques and to develop selection tools. © 2014 EVJ Ltd.

Fluor Hanford Project Focused Progress at Hanford

International Nuclear Information System (INIS)

HANSON, R.D.

2000-01-01

Fluor Hanford is making significant progress in accelerating cleanup at the Hanford site. This progress consistently aligns with a new strategic vision established by the U.S. Department of Energy's Richland Operations Office (RL)

Progressive multiple sclerosis: from pathogenic mechanisms to treatment.

Science.gov (United States)

Correale, Jorge; Gaitán, María I; Ysrraelit, María C; Fiol, Marcela P

2017-03-01

During the past decades, better understanding of relapsing-remitting multiple sclerosis disease mechanisms have led to the development of several disease-modifying therapies, reducing relapse rates and severity, through immune system modulation or suppression. In contrast, current therapeutic options for progressive multiple sclerosis remain comparatively disappointing and challenging. One possible explanation is a lack of understanding of pathogenic mechanisms driving progressive multiple sclerosis. Furthermore, diagnosis is usually retrospective, based on history of gradual neurological worsening with or without occasional relapses, minor remissions or plateaus. In addition, imaging methods as well as biomarkers are not well established. Magnetic resonance imaging studies in progressive multiple sclerosis show decreased blood-brain barrier permeability, probably reflecting compartmentalization of inflammation behind a relatively intact blood-brain barrier. Interestingly, a spectrum of inflammatory cell types infiltrates the leptomeninges during subpial cortical demyelination. Indeed, recent magnetic resonance imaging studies show leptomeningeal contrast enhancement in subjects with progressive multiple sclerosis, possibly representing an in vivo marker of inflammation associated to subpial demyelination. Treatments for progressive disease depend on underlying mechanisms causing central nervous system damage. Immunity sheltered behind an intact blood-brain barrier, energy failure, and membrane channel dysfunction may be key processes in progressive disease. Interfering with these mechanisms may provide neuroprotection and prevent disability progression, while potentially restoring activity and conduction along damaged axons by repairing myelin. Although most previous clinical trials in progressive multiple sclerosis have yielded disappointing results, important lessons have been learnt, improving the design of novel ones. This review discusses mechanisms involved

Toxic β-Amyloid (Aβ) Alzheimer's Ion Channels: From Structure to Function and Design

Science.gov (United States)

Nussinov, Ruth

2012-02-01

Full-length amyloid beta peptides (Aβ1-40/42) form neuritic amyloid plaques in Alzheimer's disease (AD) patients and are implicated in AD pathology. Recent biophysical and cell biological studies suggest a direct mechanism of amyloid beta toxicity -- ion channel mediated loss of calcium homeostasis. Truncated amyloid beta fragments (Aβ11-42 and Aβ17-42), commonly termed as non-amyloidogenic are also found in amyloid plaques of Alzheimer's disease (AD) and in the preamyloid lesions of Down's syndrome (DS), a model system for early onset AD study. Very little is known about the structure and activity of these smaller peptides although they could be key AD and DS pathological agents. Using complementary techniques of explicit solvent molecular dynamics (MD) simulations, atomic force microscopy (AFM), channel conductance measurements, cell calcium uptake assays, neurite degeneration and cell death assays, we have shown that non-amyloidogenic Aβ9-42 and Aβ17-42 peptides form ion channels with loosely attached subunits and elicit single channel conductances. The subunits appear mobile suggesting insertion of small oligomers, followed by dynamic channel assembly and dissociation. These channels allow calcium uptake in APP-deficient cells and cause neurite degeneration in human cortical neurons. Channel conductance, calcium uptake and neurite degeneration are selectively inhibited by zinc, a blocker of amyloid ion channel activity. Thus truncated Aβ fragments could account for undefined roles played by full length Aβs and provide a novel mechanism of AD and DS pathology. The emerging picture from our large-scale simulations is that toxic ion channels formed by β-sheets are highly polymorphic, and spontaneously break into loosely interacting dynamic units (though still maintaining ion channel structures as imaged with AFM), that associate and dissociate leading to toxic ion flux. This sharply contrasts intact conventional gated ion channels that consist of tightly

Building a progressive vertical integration

International Nuclear Information System (INIS)

Charette, D.

2008-01-01

AAER Inc. is a Quebec-based company that manufactures turbines using proven European designs. This presentation discussed the company's business model. The company places an emphasis on identifying strategic and key components currently available for its turbines. Market analyses are performed in order to determine ideal suppliers and define business strategies and needs. The company invests in long-term relationships with its suppliers. Business partners for AAER are of a similar size and have a mutual understanding and respect for the company's business practices. Long-term agreements with suppliers are signed in order to ensure reliability and control over costs. Progressive vertical integration has been achieved by progressively manufacturing key components and integrating a North American supply chain. The company's secure supply chain and progressive vertical integration has significantly reduced financial costs and provided better quality control. It was concluded that vertical integration has also allowed AAER to provide better customer service and reduce transportation costs. tabs., figs

Progress in optics

CERN Document Server

Wolf, Emil

2015-01-01

The Progress in Optics series contains more than 300 review articles by distinguished research workers, which have become permanent records for many important developments, helping optical scientists and optical engineers stay abreast of their fields. Comprehensive, in-depth reviewsEdited by the leading authority in the field

Kant’s Theory of Progress

OpenAIRE

McCloughan, Meade

2008-01-01

My topic is Kant’s theory of historical progress. My approach is primarily textual and contextual. I analyse in some detail Kant’s three most important essays on the topic: ‘Idea for a Universal History’, the third part of ‘Theory and Practice’ and the second part of The Conflict of the Faculties. I devote particular attention to the Kant-Herder debate about progress, but also discuss Rousseau, Mendelssohn, Hegel and others. In presenting, on Kant’s behalf, a strong case for his theory of pro...

Biogas Opportunities Roadmap Progress Report

Energy Technology Data Exchange (ETDEWEB)

None, None

2015-12-01

In support of the Obama Administration's Climate Action Plan, the U.S. Department of Energy, the U.S. Environmental Protection Agency, and U.S. Department of Agriculture jointly released the Biogas Opportunities Roadmap Progress Report, updating the federal government's progress to reduce methane emissions through biogas systems since the Biogas Opportunities Roadmap was completed by the three agencies in July 2014. The report highlights actions taken, outlines challenges and opportunities, and identifies next steps to the growth of a robust biogas industry.

Progression of MDS-UPDRS Scores Over Five Years in De Novo Parkinson Disease from the Parkinson's Progression Markers Initiative Cohort.

Science.gov (United States)

Holden, Samantha K; Finseth, Taylor; Sillau, Stefan H; Berman, Brian D

2018-01-01

The Movement Disorder Society Unified Parkinson Disease Rating Scale (MDS-UDPRS) is a commonly used tool to measure Parkinson disease (PD) progression. Longitudinal changes in MDS-UPDRS scores in de novo PD have not been established. Determine progression rates of MDS-UPDRS scores in de novo PD. 362 participants from the Parkinson's Progression Markers Initiative, a multicenter longitudinal cohort study of de novo PD, were included. Longitudinal progression of MDS-UPDRS total and subscale scores were modeled using mixed model regression. MDS-UPDRS scores increased in a linear fashion over five years in de novo PD. MDS-UPDRS total score increased an estimated 4.0 points/year, Part I 0.25 points/year, Part II 1.0 points/year, and Part III 2.4 points/year. The expected average progression of MDS-UPDRS scores in de novo PD from this study can assist in clinical monitoring and provide comparative data for detection of disease modification in treatment trials.

Progressive Finland sees progress with nuclear projects

Energy Technology Data Exchange (ETDEWEB)

Dalton, David [NucNet, Brussels (Belgium)

2016-02-15

The Finnish Hanhikivi-1 reactor project is firmly on track and a licence has been granted for construction of a final disposal facility for spent nuclear fuel - the first final repository in the world to enter the construction phase. Significant progress has been made with plans for Finland to build its sixth nuclear reactor unit at Hanhikivi. Fennovoima's licensing manager Janne Liuko said the company expects to receive the construction licence for the Generation III+ Hanhikivi-1 plant in late 2017. The application was submitted to the Finnish Ministry of Employment and the Economy in June 2015.

Assessment of a progressive electricity tax

International Nuclear Information System (INIS)

2000-01-01

Progressive electricity tax implies that the tax rate increases with consumption so that the tax paid per kWh consumed increases when the consumption increases beyond a certain level. This elucidation discusses principal and practical aspects of such a tax. It is advised against the establishment of a progressive electricity tax. The objections are of principal, economical and administrative character

Optimal tax progressivity in imperfect labour markets

DEFF Research Database (Denmark)

Sørensen, Peter Birch

1999-01-01

that there may be an optimal degree of tax progressivity where the marginal welfare gain from reduced involuntary unemployment is just offset by the marginal welfare loss from lower productivity. This paper sets up four different models of an imperfect labour market in order to identify the degree of tax......All modern labour market theories capable of explaining involuntary unemployment as an equilibrium phenomenon imply that increased income tax progressivity reduces unemployment, but they also imply that higher progressivity tends to reduce work effort and labour productivity. This suggests...

Human amyloidogenic light chain proteins result in cardiac dysfunction, cell death, and early mortality in zebrafish.

Science.gov (United States)

Mishra, Shikha; Guan, Jian; Plovie, Eva; Seldin, David C; Connors, Lawreen H; Merlini, Giampaolo; Falk, Rodney H; MacRae, Calum A; Liao, Ronglih

2013-07-01

Systemic amyloid light-chain (AL) amyloidosis is associated with rapidly progressive and fatal cardiomyopathy resulting from the direct cardiotoxic effects of circulating AL light chain (AL-LC) proteins and the indirect effects of AL fibril tissue infiltration. Cardiac amyloidosis is resistant to standard heart failure therapies, and, to date, there are limited treatment options for these patients. The mechanisms underlying the development of cardiac amyloidosis and AL-LC cardiotoxicity are largely unknown, and their study has been limited by the lack of a suitable in vivo model system. Here, we establish an in vivo zebrafish model of human AL-LC-induced cardiotoxicity. AL-LC isolated from AL cardiomyopathy patients or control nonamyloidogenic LC protein isolated from multiple myeloma patients (Con-LC) was directly injected into the circulation of zebrafish at 48 h postfertilization. AL-LC injection resulted in impaired cardiac function, pericardial edema, and increased cell death relative to Con-LC, culminating in compromised survival with 100% mortality within 2 wk, independent of AL fibril deposition. Prior work has implicated noncanonical p38 MAPK activation in the pathogenesis of AL-LC-induced cardiotoxicity, and p38 MAPK inhibition via SB-203580 rescued AL-LC-induced cardiac dysfunction and cell death and attenuated mortality in zebrafish. This in vivo zebrafish model of AL-LC cardiotoxicity demonstrates that antagonism of p38 MAPK within the AL-LC cardiotoxic signaling response may serve to improve cardiac function and mortality in AL cardiomyopathy. Furthermore, this in vivo model system will allow for further study of the molecular underpinnings of AL cardiotoxicity and identification of novel therapeutic strategies.

Nondestructive Evaluation Program: Progress in 1986

International Nuclear Information System (INIS)

1987-07-01

The increasing cost of equipment for power generating plants and the potential increases in productivity and safety available through rapidly developing Nondestructive Evaluation (NDE) technology led EPRI to initiate a Nondestructive Evaluation Program in 1974. To date, the major focus has been on light water reactor inspection problems; however, increased application to other systems is now under way. This report presents a comprehensive review of the EPRI effort in the NDE area. Most of the report consists of contractor-supplied progress reports on each current project. An organizational plan of the program is presented in overview. In addition, organization from several viewpoints is presented, e.g., in-service inspection operators, R and D personnel, and utility representatives. The report summarizes significant progress made since the previous EPRI Special Report NP-4315-SR was issued in May 1986. Section 1 contains information about the program organization, and the sections that follow contain contractor-supplied progress reports of each current project. The progress reports are grouped by plant components - pipe, pressure vessel, steam generator and boiler tubes, and turbine. In addition, Part 6 is devoted to discussions of technology transfer

Shifting closeness: interpersonal effects of personal goal progress.

Science.gov (United States)

Fitzsimons, Gráinne M; Fishbach, Ayelet

2010-04-01

In this article, we examine how the shifting motivational priority of personal goals affects relationship closeness. We hypothesize that people will draw closer to significant others who are instrumental (vs. noninstrumental) for a goal that has not been progressing well-a goal that is thus high in motivational priority. Once the goal has progressed successfully, we predict that people will cease to draw closer to instrumental others. Five studies support these predictions by showing that the impact of goal progress on reduced preference for instrumental others (Experiment 1) depends on the framing of progress as partial attainment (vs. greater commitment, Experiment 2) and the intention to balance across goals (vs. focus on one goal; Experiments 3-4). We find that moving away from instrumental others post progress is functional, in that it allows for drawing closer to those who are instrumental for alternative goals (Experiment 5).

Protein/lipid coaggregates are formed during α-synuclein-induced disruption of lipid bilayers

DEFF Research Database (Denmark)

van Maarschalkerweerd, Andreas; Vetri, Valeria; Langkilde, Annette Eva

2014-01-01

Amyloid formation is associated with neurodegenerative diseases such as Parkinson's disease (PD). Significant α-synuclein (αSN) deposition in lipid-rich Lewy bodies is a hallmark of PD. Nonetheless, an unraveling of the connection between neurodegeneration and amyloid fibrils, including the molec......Amyloid formation is associated with neurodegenerative diseases such as Parkinson's disease (PD). Significant α-synuclein (αSN) deposition in lipid-rich Lewy bodies is a hallmark of PD. Nonetheless, an unraveling of the connection between neurodegeneration and amyloid fibrils, including...... the molecular mechanisms behind potential amyloid-mediated toxic effects, is still missing. Interaction between amyloid aggregates and the lipid cell membrane is expected to play a key role in the disease progress. Here, we present experimental data based on hybrid analysis of two-photon-microscopy, solution...... small-angle X-ray scattering and circular dichroism data. Data show in real time changes in liposome morphology and stability upon protein addition and reveal that membrane disruption mediated by amyloidogenic αSN is associated with dehydration of anionic lipid membranes and stimulation of protein...

Natural Phytochemicals in the Treatment and Prevention of Dementia: An Overview

Directory of Open Access Journals (Sweden)

Rosaliana Libro

2016-04-01

Full Text Available The word dementia describes a class of heterogeneous diseases which etiopathogenetic mechanisms are not well understood. There are different types of dementia, among which, Alzheimer’s disease (AD, vascular dementia (VaD, dementia with Lewy bodies (DLB and frontotemporal dementia (FTD are the more common. Currently approved pharmacological treatments for most forms of dementia seem to act only on symptoms without having profound disease-modifying effects. Thus, alternative strategies capable of preventing the progressive loss of specific neuronal populations are urgently required. In particular, the attention of researchers has been focused on phytochemical compounds that have shown antioxidative, anti-amyloidogenic, anti-inflammatory and anti-apoptotic properties and that could represent important resources in the discovery of drug candidates against dementia. In this review, we summarize the neuroprotective effects of the main phytochemicals belonging to the polyphenol, isothiocyanate, alkaloid and cannabinoid families in the prevention and treatment of the most common kinds of dementia. We believe that natural phytochemicals may represent a promising sources of alternative medicine, at least in association with therapies approved to date for dementia.

The ubiquitin-proteasome pathway mediates gelsolin protein downregulation in pancreatic cancer

NARCIS (Netherlands)

Ni, Xiao-Guang; Zhou, Lu; Wang, Gui-Qi; Liu, Shang-Mei; Bai, Xiao-Feng; Liu, Fang; Peppelenbosch, Maikel P.; Zhao, Ping

2008-01-01

A well-known observation with respect to cancer biology is that transformed cells display a disturbed cytoskeleton, The underlying mechanisms, however, remain only partly understood. In an effort to identify possible mechanisms, we compared the proteome of pancreatic cancer with matched normal

Progressive Retirement Programme

CERN Document Server

HR Department

2009-01-01

Following the Standing Concertation Committee meeting of 2 December 2008, please note that the Progressive Retirement Programme has been extended by one year, i.e. until 31 March 2010. Further information is available on : https://hr-services.web.cern.ch/hr-services/services-Ben/prp/prp.asp HR Department, tel. 73903

Progress report 1979

International Nuclear Information System (INIS)

1980-12-01

This progress report deals with technical and research work done at the AAEC Research Establishment in the twelve month period ending September 30, 1979. Work done in the following research divisions is reported: Applied Maths and Computing, Chemical Technology, Engineering Research, Environmental Science, Instrumentation and Control, Isotope, Materials and Physics

"Paideia," Progress, Puzzlement

Science.gov (United States)

Hrachovec, Herbert

2018-01-01

Platonic "paideia" is a mainstream concept in traditional philosophy and humanistic circles generally. It is closely connected with social progress brought about by the dynamics of enlightenment and self-fulfillment, symbolized by the allegory of the cave. The main contention of this paper is that the philosophical grammar of this simile…

Construal operations of the English progressive construction

DEFF Research Database (Denmark)

Jensen, Kim Ebensgaard

2011-01-01

present paper provides an overview of construal operations that are likely to be at play in the construction of the aspectual and actional meaning components of the progressive construction. The discussion also involves instances of the progressive construction, which display low semantic compatibility...

Progression of Liver Disease

Science.gov (United States)

... Legacy Society Make Gifts of Stock Donate Your Car Personal Fundraising Partnership & Support Share Your Story Spread the Word Give While You Shop Contact Us Donate Now The Progression of Liver ...

Progress in JT-60 joint research

International Nuclear Information System (INIS)

Kimura, Haruyuki; Kikuchi, Mitsuru; Inutake, Masaaki

2007-01-01

It consists of five chapters; 1) introduction, 2) management system of joint plan and researches, 3) progress of joint researches, 4) results of researches and 5) summary. The second chapter stated the structure of management system of JT-60 joint researches, progress of management of the JT-60 experimental theme system, invitation the public to joint researches and selection of the subjects. The progress of joint researches contained the number of subjects, research members and organizations, change of joint research fields, remote control system of experiments, analysis code group, and number of reports. The main results of researches such as development of operation without center solenoid, Magneto-Hydro-Dynamics (MHD) control by electron cyclotron wave, plasma-wall interaction, application of laser technologies to plasma measurement, and comparison between tokamak and helical are reported. (S.Y.)

Progress report, Physics Division

International Nuclear Information System (INIS)

1986-03-01

This report reviews events and progress in the following areas: development of the TASCC facility; experimental and theoretical nuclear physics research; radionuclide standardization; condensed matter research; applied mathematics; and computer facility operation

Scientific progress without increasing verisimilitude: In response to Niiniluoto.

Science.gov (United States)

Rowbottom, Darrell P

2015-06-01

First, I argue that scientific progress is possible in the absence of increasing verisimilitude in science's theories. Second, I argue that increasing theoretical verisimilitude is not the central, or primary, dimension of scientific progress. Third, I defend my previous argument that unjustified changes in scientific belief may be progressive. Fourth, I illustrate how false beliefs can promote scientific progress in ways that cannot be explicated by appeal to verisimilitude. Copyright © 2015 Elsevier Ltd. All rights reserved.

Recent progress on high-speed optical transmission

Directory of Open Access Journals (Sweden)

Jianjun Yu

2016-05-01

Full Text Available The recently reported high spectral efficiency (SE and high-baud-rate signal transmission are all based on digital coherent optical communications and digital signal processing (DSP. DSP simplifies the reception of advanced modulation formats and also enables the major electrical and optical impairments to be processed and compensated in the digital domain, at the transmitter or receiver side. In this paper, we summarize the research progress on high-speed signal generation and detection and also show the progress on DSP for high-speed signal detection. We also report the latest progress on multi-core and multi-mode multiplexing.

Tunneling progress on the Yucca Mountain Project

International Nuclear Information System (INIS)

Hansmire, W.H.; Munzer, R.J.

1996-01-01

The current status of tunneling progress on the Yucca Mountain Project (YMP) is presented in this paper. The Exploratory Studies Facility (ESF), a key part of the YMP, has been long in development and construction is ongoing. This is a progress report on the tunneling aspects of the ESF as of January 1, 1996. For purposes of discussion in this summary, the tunneling has progressed in four general phases. The paper describes: tunneling in jointed rock under low stress; tunneling through the Bow Ridge Fault and soft rock; tunneling through the Imbricate Fault Zone; and Tunneling into the candidate repository formation

Research progress in roles of gut microbiota and bile acid metabolism in development and progression of NAFLD

Directory of Open Access Journals (Sweden)

LU Xu

2014-11-01

Full Text Available With the prevalence of obesity and metabolic syndrome, the incidence of nonalcoholic fatty liver disease (NAFLD is increasing year by year. Studies have uncovered the important roles of gut microbiota and bile acid metabolism in the development and progression of NAFLD. The roles of gut microbiota, as well bile acid and bile acid receptors, in the development and progression of NAFLD are highlighted.

76 FR 37805 - Progress Energy Carolinas; Notice of Meeting

Science.gov (United States)

2011-06-28

... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Project No. 2206-030] Progress Energy Carolinas; Notice of Meeting On May 31, 2011, Progress Energy Carolinas (Progress Energy), licensee for the... National Marine Fisheries Service (NMFS) and staff to discuss what is needed to complete formal...

Epidemiological and biochemical aspects of progression in multiple sclerosis

NARCIS (Netherlands)

Koch, Marcus Werner

2008-01-01

Patients with a progressive form of multiple sclerosis have the worst prognosis. They can expect that their symptoms will steadily worsen, and there is currently no treatment that has a proven effect on progressive multiple sclerosis. The underlying pathophysiology of the progressive forms of

Selective alterations of the host cell architecture upon infection with parvovirus minute virus of mice

International Nuclear Information System (INIS)

Nueesch, Juerg P.F.; Lachmann, Sylvie; Rommelaere, Jean

2005-01-01

During a productive infection, the prototype strain of parvovirus minute virus of mice (MVMp) induces dramatic morphological alterations to the fibroblast host cell A9, resulting in cell lysis and progeny virus release. In order to understand the mechanisms underlying these changes, we characterized the fate of various cytoskeletal filaments and investigated the nuclear/cytoplasmic compartmentalization of infected cells. While most pronounced effects could be seen on micro- and intermediate filaments, manifest in dramatic rearrangements and degradation of filamentous (F-)actin and vimentin structures, only little impact could be seen on microtubules or the nuclear envelope during the entire monitored time of infection. To further analyze the disruption of the cytoskeletal structures, we investigated the viral impact on selective regulatory pathways. Thereby, we found a correlation between microtubule stability and MVM-induced phosphorylation of α/β tubulin. In contrast, disassembly of actin filaments late in infection could be traced back to the disregulation of two F-actin associated proteins gelsolin and Wiscott-Aldrich Syndrome Protein (WASP). Thereby, an increase in the amount of gelsolin, an F-actin severing protein was observed during infection, accounting for the disruption of stress fibers upon infection. Concomitantly, the actin polymerization activity also diminished due to a loss of WASP, the activator protein of the actin polymerization machinery the Arp2/3 complex. No effects could be seen in amount and distribution of other F-actin regulatory factors such as cortactin, cofilin, and profilin. In summary, the selective attack of MVM towards distinct host cell cytoskeletal structures argues for a regulatory feature during infection, rather than a collapse of the host cell as a mere side effect of virus production

Proteomic analysis of cerebrospinal fluid in canine cervical spondylomyelopathy.

Science.gov (United States)

Martin-Vaquero, Paula; da Costa, Ronaldo C; Allen, Matthew J; Moore, Sarah A; Keirsey, Jeremy K; Green, Kari B

2015-05-01

Prospective study. To identify proteins with differential expression in the cerebrospinal fluid (CSF) from 15 clinically normal (control) dogs and 15 dogs with cervical spondylomyelopathy (CSM). Canine CSM is a spontaneous, chronic, compressive cervical myelopathy similar to human cervical spondylotic myelopathy. There is a limited knowledge of the molecular mechanisms underlying these conditions. Differentially expressed CSF proteins may contribute with novel information about the disease pathogenesis in both dogs and humans. Protein separation was performed with 2-dimensional electrophoresis. A Student t test was used to detect significant differences between groups (P liquid chromatography tandem mass spectrometry. A total of 96 spots had a significant average change of at least 1.25-fold in 1 of the 3 comparisons. Compared with the CSF of control dogs, CSM-affected dogs demonstrated increased CSF expression of 8 proteins including vitamin D-binding protein, gelsolin, creatine kinase B-type, angiotensinogen, α-2-HS-glycoprotein, SPARC (secreted protein, acidic, rich in cysteine), calsyntenin-1, and complement C3, and decreased expression of pigment epithelium-derived factor, prostaglandin-H2 D-isomerase, apolipoprotein E, and clusterin. In the CSF of CSM-affected dogs, corticosteroid treatment increased the expression of haptoglobin, transthyretin isoform 2, cystatin C-like, apolipoprotein E, and clusterin, and decreased the expression of angiotensinogen, α-2-HS-glycoprotein, and gelsolin. Many of the differentially expressed proteins are associated with damaged neural tissue, bone turnover, and/or compromised blood-spinal cord barrier. The knowledge of the protein changes that occur in CSM and upon corticosteroid treatment of CSM-affected patients will aid in further understanding the pathomechanisms underlying this disease. N/A.

Recent progress on laser acceleration research

International Nuclear Information System (INIS)

Nakajima, Kazuhisa; Dewa, Hideki; Hosokai, Tomonao; Kanazawa, Shuhei; Kando, Masaki; Kondoh, Shuji; Kotaki, Hideyuki

2000-01-01

Recently there has been a tremendous experimental progress in ultrahigh field particle acceleration driven by ultraintense laser pulses in plasmas. A design of the laser wakefield accelerators aiming at GeV energy gains is discussed by presenting our recent progress on the laser wakefield acceleration experiments, the developments of high quality electron beam injectors and the capillary plasma waveguide for optical guiding of ultrashort intense laser pulses. (author)

Progressive Decrease of Peripapillary Angioflow Vessel Density During Structural and Visual Field Progression in Early Primary Open-angle Glaucoma.

Science.gov (United States)

Holló, Gábor

2017-07-01

To present a case of early primary open-angle glaucoma in which retinal nerve fiber layer thickness (RNFLT), ganglion cell complex (GCC), and visual field progression were accompanied with significant progression of peripapillary angioflow vessel density (PAFD) measured with optical coherence tomographic angiography. A 68-year-old female patient who was under topical intraocular pressure (IOP) lowering medication for 20 years for ocular hypertension of the right and preperimetric primary open-angle glaucoma of the left eye (with reproducible inferotemporal and superotemporal neuroretinal rim and RNFL loss) was prospectively imaged with the AngioVue OCT for RNFLT, GCC thickness, and PAFD, and investigated with the Octopus Normal G2 visual field test on the same days at 6-month intervals for 18 months, while the IOP of the left eye escaped from control. IOP of the left eye fluctuated between 14 and 30 mm Hg in the study period. RNFLT, GCC thickness, and peripapillary PAFD all decreased significantly (linear regression analysis, P=0.030, 0.040, and 0.020, respectively), and a significant 2.1 dB/y progression was seen for a superior visual field cluster. The RNFLT, peripapillary PAFD, and visual field of the right eye remained normal and unchanged. In our case IOP elevation, glaucomatous visual field conversion, and structural progression were accompanied with significant progressive decrease of peripapillary PAFD. The simultaneous thinning of RNFLT and GCC and decrease of peripapillary PAFD suggest that PAFD may potentially be an additional indicator of early progression in primary open-angle glaucoma.

Progress for the Paralyzed

Science.gov (United States)

... Contents Latest Advances Help People Regain Function and Independence Founded in 2000, the National Institute for Biomedical ... More "NIBIB Robotics" Articles Progress for the Paralyzed / College Athlete Stands Again…On His Own! / Coffee to ...

Progressivity Enhanced

Directory of Open Access Journals (Sweden)

Marko Hren

2013-09-01

Full Text Available Rather than a scientific text, the author contributes a concise memorandum from the originator of the idea who has managed the campaign for the conversion of the military barracks into a creative cluster between 1988 and 2002, when he parted ways with Metelkova due to conflicting views on the center’s future. His views shed light on a distant period of time from a perspective of a participant–observer. The information is abundantly supported by primary sources, also available online. However, some of the presented hypotheses are heavily influenced by his personal experiences of xenophobia, elitism, and predatorial behavior, which were already then discernible on the so-called alternative scene as well – so much so that they obstructed the implementation of progressive programs. The author claims that, in spite of the substantially different reality today, the myths and prejudices concerning Metelkova must be done away with in order to enhance its progressive nature. Above all, the paper calls for an objective view on internal antagonisms, mainly originating in deep class divisions between the users. These make a clear distinction between truly marginal ndividuals and the overambitious beau-bourgeois, as the author labels the large part of users of Metelkova of »his« time. On these grounds, he argues for a robust approach to ban all forms of xenophobia and self-ghettoization.

Communication of nuclear data progress

International Nuclear Information System (INIS)

2001-01-01

This is the 26th issue of Communication of Nuclear Data Progress (CNDP), in which the progress and achievements in nuclear data field from the last year up to now in China are carried. It includes the measurements of 71 Ga, 94 Zn, 191 Ir, 174 Hf(n, γ) and 114 Cd(n, 2n) cross sections, fission product yields of n + 235,238 U, DPA cross section calculated with UNF code, fission barrier parameter evaluation of some nuclides, production and transmission of covariance in the evaluation processing of fission yield data and transition analysis of Ne-like Ge XXIII

Progressive posterior cortical dysfunction

Directory of Open Access Journals (Sweden)

Fábio Henrique de Gobbi Porto

Full Text Available Abstract Progressive posterior cortical dysfunction (PPCD is an insidious syndrome characterized by prominent disorders of higher visual processing. It affects both dorsal (occipito-parietal and ventral (occipito-temporal pathways, disturbing visuospatial processing and visual recognition, respectively. We report a case of a 67-year-old woman presenting with progressive impairment of visual functions. Neurologic examination showed agraphia, alexia, hemispatial neglect (left side visual extinction, complete Balint's syndrome and visual agnosia. Magnetic resonance imaging showed circumscribed atrophy involving the bilateral parieto-occipital regions, slightly more predominant to the right . Our aim was to describe a case of this syndrome, to present a video showing the main abnormalities, and to discuss this unusual presentation of dementia. We believe this article can contribute by improving the recognition of PPCD.

Progressive posterior cortical dysfunction

Science.gov (United States)

Porto, Fábio Henrique de Gobbi; Machado, Gislaine Cristina Lopes; Morillo, Lilian Schafirovits; Brucki, Sonia Maria Dozzi

2010-01-01

Progressive posterior cortical dysfunction (PPCD) is an insidious syndrome characterized by prominent disorders of higher visual processing. It affects both dorsal (occipito-parietal) and ventral (occipito-temporal) pathways, disturbing visuospatial processing and visual recognition, respectively. We report a case of a 67-year-old woman presenting with progressive impairment of visual functions. Neurologic examination showed agraphia, alexia, hemispatial neglect (left side visual extinction), complete Balint’s syndrome and visual agnosia. Magnetic resonance imaging showed circumscribed atrophy involving the bilateral parieto-occipital regions, slightly more predominant to the right. Our aim was to describe a case of this syndrome, to present a video showing the main abnormalities, and to discuss this unusual presentation of dementia. We believe this article can contribute by improving the recognition of PPCD. PMID:29213665

Progress report 1978

International Nuclear Information System (INIS)

1979-01-01

The Studsvik Science Research Laboratory herewith presents its progress report for 1978. The report summarizes the current projects carried out by the research groups working at the laboratory. Projects within the following fields are presented: neutron physics, neutron absorption and scattering, radiation chemistry, radiation damage studies, radioactivity and theoretical studies of condensed matter. (E.R.)

Study on severe fuel damage and in-vessel melt progression

International Nuclear Information System (INIS)

Kim, Hee Dong; Kim, Sang Baik; Lee, Gyu Jung

1992-06-01

In-vessel core melt progression describes the progression of the state of a reactor core from core uncovery up to reactor vessel melt through in uncovered accidents or through temperature stabilization in accidents recovered by core reflooding. Melt progression can be thought as two parts; early melt progression and late melt progression. Early phase of core melt progression includes the progression of core material melting and relocation, which mostly consist of metallic materials. On the other hand, the late phase of core melt progression involves ceramic material melt and relocation to the lower plenum and heat-up the reactor vessel lower head. A large number of information are available for the early melt progression through experiments such as SFD, DF, FLHT test and utilized in the severe accident analysis codes. However, understanding of the late phase melt progression phenomenology is based primary on TMI-2 core examinations and not much experimental information is available. Especilally, the great uncertainties exist in vessel failure mode, melt composition, mass, and temperature. Further research is planned to perform to reduce the uncertainties in understanding of core melt down accidents as parts of long term melt progression research program. A study on the core melt progression at KAERI has been being performed through the Severe Accident Research Program with USNRC. KAERI staff had participated in the PBF SFD experiments at INEL and analyses of experiments were performed using SCDAP code. Experiments of core melt program have not been carried out at KAERI yet. It is planned that further research on core melt down accidents will be performed, which is related to design of future generations of nuclear reactors as parts of long-term project for improvement of nuclear reactor safety. (Author)

Home Environmental Factors Influencing Performance and Progress ...

African Journals Online (AJOL)

Our findings support other studies which found that parents' educational level and income level have a bearing on school progress and performance. Contrary to most research findings mother tongue instruction did not eme1rge as an important explanatory factor on school progress and performance, however; home ...

Progress in MELCOR development and assessment

International Nuclear Information System (INIS)

Summers, R.M.; Kmetyk, L.N.; Cole, R.K. Jr.; Smith, R.C.; Elsbernd, A.E.; Stuart, D.S.; Thompson, S.L.

1995-01-01

MELCOR models the progression of severe accidents in light water reactor nuclear power plants. Recent efforts in MELCOR development to incorporate CORCON-Mod3 models for core-concrete interactions, new models for advanced reactors, and improvements to several other existing models have resulted in release of MELCOR 1.8.3. In addition, continuing efforts to expand the code assessment database have filled in many of the gaps in phenomenological coverage. Efforts are now under way to develop models for chemical interactions of fission products with structural surfaces and for reactions of iodine in the presence of water, and work is also in progress to improve models for the scrubbing of fission products by water pools, the chemical reactions of boron carbide with steam, and the coupling of flow blockages with the hydrodynamics. Several code assessment analyses are in progress, and more are planned

Self-reported Medication Adherence and CKD Progression

Directory of Open Access Journals (Sweden)

Esteban A. Cedillo-Couvert

2018-05-01

Full Text Available Introduction: In the general population, medication nonadherence contributes to poorer outcomes. However, little is known about medication adherence among adults with chronic kidney disease (CKD. We evaluated the association of self-reported medication adherence with CKD progression and all-cause death in patients with CKD. Methods: In this prospective observational study of 3305 adults with mild-to-moderate CKD enrolled in the Chronic Renal Insufficiency Cohort (CRIC Study, the baseline self-reported medication adherence was assessed by responses to 3 questions and categorized as high, medium, and low. CKD progression (50% decline in eGFR or incident end-stage renal disease and all-cause death were measured using multivariable Cox proportional hazards. Results: Of the patients, 68% were categorized as high adherence, 17% medium adherence, and 15% low adherence. Over a median follow-up of 6 years, there were 969 CKD progression events and 675 deaths. Compared with the high-adherence group, the low-adherence group experienced increased risk for CKD progression (hazard ratio = 1.27, 95% confidence interval = 1.05, 1.54 after adjustment for sociodemographic and clinical factors, cardiovascular medications, number of medication types, and depressive symptoms. A similar association existed between low adherence and all-cause death, but did not reach standard statistical significance (hazard ratio = 1.14 95% confidence interval = 0.88, 1.47. Conclusion: Baseline self-reported low medication adherence was associated with an increased risk for CKD progression. Future work is needed to better understand the mechanisms underlying this association and to develop interventions to improve adherence. Keywords: CKD, death, medication adherence, progression

Current progress in NIF target concepts

International Nuclear Information System (INIS)

Gobby, P.L.; Foreman, L.R.; Thoma, D.J.; Jacobson, L.A.; Hollis, R.V.; Barrera, J.; Mitchell, M.A.; Salazar, M.A.; Salzer, L.J.

1996-01-01

Target concepts for the National Ignition Facility (NIF) require progress in the art and science of target fabrication. Three distinct issues are addressed: beryllium fuel capsules, foam-buffered direct drive, and high-density gas-filled hohlraums. In all cases experiments on the existing Nova laser at LLNL are either in progress or planned for the near future to test the various concepts. Consequently, target fabrication must be able to deliver targets appropriate for each

Progression of Liver Disease

Science.gov (United States)

... Liver Function Tests Clinical Trials Liver Transplant FAQs Medical Terminology Diseases of the Liver Alagille Syndrome Alcohol-Related ... the Liver The Progression of Liver Disease FAQs Medical Terminology HOW YOU CAN HELP Sponsorship Ways to Give ...

Progression of CT scan findings in Rett syndrome

Energy Technology Data Exchange (ETDEWEB)

Suzuki, Hisaharu; Hirayama, Yoshito; Sakuragawa, Norio; Arima, Masataka (National Center of Neurology and Psychiatry, Kodaira, Tokyo (Japan))

1989-07-01

Progression of the lesions revealed by CT scan was observed in five girls with Rett syndrome. The most distinct and common finding was progressive dilatation of Sylvian fissures, frontal extracerebral space, interhemispheric fissure, and sulci mainly in frontal lobe. It may indicate progressive lesion in the frontal and the temporal lobes. In addition, dilatation of the anterior horns of the lateral ventricles and the third ventricle was noted in some cases. Brainstem and cerebellum were small at any age with some morphological development as the patients became elder. Neither malformations nor abnormalities in density were found in any case. It is concluded that the main lesion of Rett syndrome on CT scan is progressive and localized in the frontal and the temporal lobes. (author).

Progress in the last decade in our understanding of primary progressive aphasia

Directory of Open Access Journals (Sweden)

Ratnavalli Ellajosyula

2010-10-01

Full Text Available Primary progressive aphasia (PPA is a focal neurodegeneration of the brain affecting the language network. Patients can have isolated language impairment for years without impairment in other areas. PPA is classified as primary progressive nonfluent aphasia (PNFA, semantic dementia (SD, and logopenic aphasia, which have distinct patterns of atrophy on neuroimaging. PNFA and SD are included under frontotemporal lobar degenerations. PNFA patients have effortful speech with agrammatism, which is frequently associated with apraxia of speech and demonstrate atrophy in the left Broca′s area and surrounding region on neuroimaging. Patients with SD have dysnomia with loss of word and object (or face meaning with asymmetric anterior temporal lobe atrophy. Logopenic aphasics have word finding difficulties with frequent pauses in conversation, intact grammar, and word comprehension but impaired repetition for sentences. The atrophy is predominantly in the left posterior temporal and inferior parietal regions. Recent studies have described several progranulin mutations on chromosome 17 in PNFA. The three clinical syndromes have a less robust relationship to the underlying pathology, which is heterogeneous and includes tauopathy, ubiquitinopathy, Pick′s disease, corticobasal degeneration, progressive supranuclear palsy, and Alzheimer′s disease. Recent studies, however, seem to indicate that a better characterization of the clinical phenotype (apraxic, agrammatic, semantic, logopenic, jargon increases the predictive value of the underlying pathology. Substantial advances have been made in our understanding of PPAs but developing new biomarkers is essential in making accurate causative diagnoses in individual patients. This is critically important in the development and evaluation of disease-modifying drugs.

Electron-beam-fusion progress report, January--June 1976

International Nuclear Information System (INIS)

1976-10-01

Research progress is reported for the following areas: (1) Proto I, (2) Proto II, (3) EBFA, (4) power flow, (5) contract progress reports, (6) progress in the Sandia program, (7) repetitively operated pulse generator development, (8) electron beam power from inductive storage, (9) fusion target design, (10) beam physics research, (11) power flow, (12) heavy ion fusion, (13) particle beam source development, (14) beam target interaction and target response studies, (15) diagnostic development, and (16) hybrid systems

Genes Involved in Oxidation and Prostate Cancer Progression

National Research Council Canada - National Science Library

Platz, Elizabeth A

2008-01-01

.... Using incidence-density sampling, we selected 524 men matched on age, race, and pathological stage and grade who had not progressed by the date of the matched case's progression. Noncancer tissue...

Small molecule proteostasis regulators that reprogram the ER to reduce extracellular protein aggregation

Science.gov (United States)

Plate, Lars; Cooley, Christina B; Chen, John J; Paxman, Ryan J; Gallagher, Ciara M; Madoux, Franck; Genereux, Joseph C; Dobbs, Wesley; Garza, Dan; Spicer, Timothy P; Scampavia, Louis; Brown, Steven J; Rosen, Hugh; Powers, Evan T; Walter, Peter; Hodder, Peter; Wiseman, R Luke; Kelly, Jeffery W

2016-01-01

Imbalances in endoplasmic reticulum (ER) proteostasis are associated with etiologically-diverse degenerative diseases linked to excessive extracellular protein misfolding and aggregation. Reprogramming of the ER proteostasis environment through genetic activation of the Unfolded Protein Response (UPR)-associated transcription factor ATF6 attenuates secretion and extracellular aggregation of amyloidogenic proteins. Here, we employed a screening approach that included complementary arm-specific UPR reporters and medium-throughput transcriptional profiling to identify non-toxic small molecules that phenocopy the ATF6-mediated reprogramming of the ER proteostasis environment. The ER reprogramming afforded by our molecules requires activation of endogenous ATF6 and occurs independent of global ER stress. Furthermore, our molecules phenocopy the ability of genetic ATF6 activation to selectively reduce secretion and extracellular aggregation of amyloidogenic proteins. These results show that small molecule-dependent ER reprogramming, achieved through preferential activation of the ATF6 transcriptional program, is a promising strategy to ameliorate imbalances in ER function associated with degenerative protein aggregation diseases. DOI: http://dx.doi.org/10.7554/eLife.15550.001 PMID:27435961

Preformed β-amyloid fibrils are destabilized by coenzyme Q10 in vitro

International Nuclear Information System (INIS)

Ono, Kenjiro; Hasegawa, Kazuhiro; Naiki, Hironobu; Yamada, Masahito

2005-01-01

Inhibition of the formation of β-amyloid fibrils (fAβ), as well as the destabilization of preformed fAβ in the CNS, would be attractive therapeutic targets for the treatment of Alzheimer's disease (AD). We reported previously that nordihydroguaiaretic acid (NDGA) and wine-related polyphenol, myricetin (Myr), inhibit fAβ formation from Aβ and destabilize preformed fAβ in vitro. Using fluorescence spectroscopic analysis with thioflavin T and electron microscopic studies, we examined the effects of coenzyme Q 10 (CoQ 10 ) on the formation, extension, and destabilization of fAβ at pH 7.5 at 37 deg C in vitro. We next compared the anti-amyloidogenic activities of CoQ 10 with NDGA and Myr. CoQ 10 dose-dependently inhibited fAβ formation from amyloid β-peptide (Aβ), as well as their extension. Moreover, it destabilized preformed fAβs. The anti-amyloidogenic effects of CoQ 10 were slightly weaker than those of NDGA and Myr. CoQ 10 could be a key molecule for the development of therapeutics for AD

NABi, a novel β-sheet breaker, inhibits Aβ aggregation and neuronal toxicity: Therapeutic implications for Alzheimer's disease.

Science.gov (United States)

Jang, Ja-Young; Rhim, Hyangshuk; Kang, Seongman

2018-01-01

Amyloid beta (Aβ) aggregates are an important therapeutic target for Alzheimer's disease (AD), a fatal neurodegenerative disease. To date, AD still remains a big challenge due to no effective treatments. Based on the property that Aβ aggregates have the cross-β-structure, a common structural feature in amyloids, we systemically designed the Aβ-aggregation inhibitor that maintains Aβ-interacting ability but removes toxic part from SOD1 (superoxide dismutase 1)-G93A. We identified NABi (Natural Aβ Binder and Aβ-aggregation inhibitor) composed of β2-3 strands, a novel breaker of Aβ aggregation, which does not self-aggregate and has no cytotoxicity at all. The NABi blocks Aβ-fibril formation in vitro and in vivo and prevents neuronal cell death, a hallmark of AD pathogenesis. Such anti-amyloidogenic properties can provide novel strategies for treating AD. Furthermore, our study provides molecular insights into the design of amyloidogenic inhibitors to cure various neurodegenerative and amyloid-associated diseases, as NABi would regulate aggregation of other toxic β-sheet proteins other than Aβ. Copyright © 2017 Elsevier B.V. All rights reserved.

A β2-microglobulin cleavage variant fibrillates at near-physiological pH

International Nuclear Information System (INIS)

Corlin, Dorthe B.; Johnsen, Christina K.; Nissen, Mogens H.; Heegaard, Niels H.H.

2009-01-01

β 2 -microglobulin (β 2 m) deposits as amyloid in dialysis-related amyloidosis (DRA), predominantly in joints. The molecular mechanisms underlying the amyloidogenicity of β 2 m are still largely unknown. In vitro, acidic conditions, pH 2 m within several days. Here, we show that amyloid fibrils are generated in less than an hour when a cleavage variant of β 2 m-found in the circulation of many dialysis patients-is exposed to pH levels (pH 6.6) occurring in joints during inflammation. Aggregation and fibrillation, including seeding effects with intact, native β 2 m were studied by Thioflavin T fluorescence spectroscopy, turbidimetry, capillary electrophoresis, and electron microscopy. We conclude that a biologically relevant variant of β 2 m is amyloidogenic at slightly acidic pH. Also, only a very small amount of preformed fibrils of this variant is required to induce fibrillation of native β 2 m. This may explain the apparent lack of detectable amounts of the variant β 2 m in extracts of amyloid from DRA patients.

Trapping of palindromic ligands within native transthyretin prevents amyloid formation

Science.gov (United States)

Kolstoe, Simon E.; Mangione, Palma P.; Bellotti, Vittorio; Taylor, Graham W.; Tennent, Glenys A.; Deroo, Stéphanie; Morrison, Angus J.; Cobb, Alexander J. A.; Coyne, Anthony; McCammon, Margaret G.; Warner, Timothy D.; Mitchell, Jane; Gill, Raj; Smith, Martin D.; Ley, Steven V.; Robinson, Carol V.; Wood, Stephen P.; Pepys, Mark B.

2010-01-01

Transthyretin (TTR) amyloidosis is a fatal disease for which new therapeutic approaches are urgently needed. We have designed two palindromic ligands, 2,2'-(4,4'-(heptane-1,7-diylbis(oxy))bis(3,5-dichloro-4,1-phenylene)) bis(azanediyl)dibenzoic acid (mds84) and 2,2'-(4,4'-(undecane-1,11-diylbis(oxy))bis(3,5-dichloro-4,1-phenylene)) bis(azanediyl)dibenzoic acid (4ajm15), that are rapidly bound by native wild-type TTR in whole serum and even more avidly by amyloidogenic TTR variants. One to one stoichiometry, demonstrable in solution and by MS, was confirmed by X-ray crystallographic analysis showing simultaneous occupation of both T4 binding sites in each tetrameric TTR molecule by the pair of ligand head groups. Ligand binding by native TTR was irreversible under physiological conditions, and it stabilized the tetrameric assembly and inhibited amyloidogenic aggregation more potently than other known ligands. These superstabilizers are orally bioavailable and exhibit low inhibitory activity against cyclooxygenase (COX). They offer a promising platform for development of drugs to treat and prevent TTR amyloidosis. PMID:21059958

Keratoconus Progression Induced by In Vitro Fertilization Treatment.

Science.gov (United States)

Yuksel, Erdem; Yalinbas, Duygu; Aydin, Bahri; Bilgihan, Kamil

2016-01-01

To evaluate patients with keratoconus who manifested progression after in vitro fertilization (IVF) treatment. Patients with keratoconus who received IVF treatment were included in this study. None of the patients became pregnant as a result of the IVF treatment. Progression of keratoconus was determined by changes in corrected distance visual acuity and/or topographic changes and subjective assessments. Three patients with keratoconus received IVF treatment and keratoconus progression was detected in all 6 eyes of the patients. The mean age of the patients was 32.3 ± 3.6 years (range: 28 to 36 years) and the mean follow-up duration was 15.6 ± 3.2 months (range: 12 to 18 months). The mean and the maximum keratometry values increased and corrected distance visual acuity decreased after 2.3 IVF treatments. Drugs used in IVF treatment increase estrogen levels, which may affect corneal biomechanics and induce progression of keratoconus. Corneal cross-linking treatment could be offered to minimize the risk of keratoconus progression before IVF treatment. Copyright 2016, SLACK Incorporated.

Central Blood Pressure and Chronic Kidney Disease Progression

Directory of Open Access Journals (Sweden)

Debbie L. Cohen

2011-01-01

Full Text Available Hypertension, diabetes, and proteinuria are well-recognized risk factors for progressive kidney function loss. However, despite excellent antihypertensive and antidiabetic drug therapies, which also often lower urinary protein excretion, there remains a significant reservoir of patients with chronic kidney disease who are at high risk for progression to end-stage kidney disease. This has led to the search for less traditional cardiovascular risk factors that will help stratify patients at risk for more rapid kidney disease progression. Among these are noninvasive estimates of vascular structure and function. Arterial stiffness, manifested by the pulse wave velocity in the aorta, has been established in a number of studies as a significant risk factor for kidney disease progression and cardiovascular endpoints. Much less well studied in chronic kidney disease are measures of central arterial pressures. In this paper we cover the physiology behind the generation of the central pulse wave contour and the studies available using these approaches and conclude with some speculations on the rationale for why measurements of central pressure may be informative for the study of chronic kidney disease progression.

Measuring progress

DEFF Research Database (Denmark)

Wahlberg, Ayo

2007-01-01

In recent years, sociological examinations of genetics, therapeutic cloning, neuroscience and tissue engineering have suggested that 'life itself' is currently being transformed through technique with profound implications for the ways in which we understand and govern ourselves and others...... in much the same way that mortality rates, life expectancy or morbidity rates can. By analysing the concrete ways in which human progress has been globally measured and taxonomised in the past two centuries or so, I will show how global stratifications of countries according to their states...

A review on primary progressive aphasia

Directory of Open Access Journals (Sweden)

Gabriel C Léger

2007-01-01

Full Text Available Gabriel C Léger1,2, Nancy Johnson31Neurology Service, Hôtel-Dieu du Centre Hospitalier de l’Univertité de Montréal, Montréal, Québec, Canada; 2Faculty of Medicine, Université de Montréal, Montréal, Québec, Canada; 3Cognitive Neurology and Alzheimer’s Disease Center, Department of Psychiatry and Behavioral Science, Northwestern University Feinberg School of Medicine, Chicago, IL, USAAbstract: Primary progressive aphasia (PPA is a neurodegenerative disease of insidious onset presenting with progressive isolated loss of language function, without significant impairment in other cognitive domains. Current diagnostic criteria require the language dysfunction to remain isolated for at least two years, and to remain the salient feature as the disease progresses, usually to involve other domains such as behavior, executive functions, and judgment. Although PPA in its early stages can usually be differentiated from probable Alzheimer’s disease (PRAD and the behavioral variant of frontotemporal lobar degeneration by the absence of significant changes in memory and behavior, and the preservation of activities daily living, progression of the disease often leads to deficits more consistent with the latter. Underlying etiologies remain heterogeneous: the neuropathological characteristics associated with frontotemporal lobar degeneration, cortocobasal degeneration, and motor neuron disease are usually found. There is a strong genetic susceptibility with affliction of first-degree relatives with similar disease in up to 40 to 50% in some series. Pathogenic mutations in genes coding for the proteins tau and progranulin have been isolated. These are leading to a better understanding of the neuropathological mechanisms and hopefully targeted disease-modifying therapy. Current therapy is limited to improving mood symptoms and targeting behavior changes as they develop. Referral to specialized centers where speech therapy, counseling, and education

Juvenile myopia progression, risk factors and interventions.

Science.gov (United States)

Myrowitz, Elliott H

2012-07-01

The development and progression of early onset myopia is actively being investigated. While myopia is often considered a benign condition it should be considered a public health problem for its visual, quality of life, and economic consequences. Nearly half of the visually impaired population in the world has uncorrected refractive errors, with myopia a high percent of that group. Uncorrected visual acuity should be screened for and treated in order to improve academic performance, career opportunities and socio-economic status. Genetic and environmental factors contribute to the onset and progression of myopia. Twin studies have supported genetic factors and research continues to identify myopia genetic loci. While multiple myopia genetic loci have been identified establishing myopia as a common complex disorder, there is not yet a genetic model explaining myopia progression in populations. Environmental factors include near work, education levels, urban compared to rural location, and time spent outdoors. In this field of study where there continues to be etiology controversies, there is recent agreement that children who spend more time outdoors are less likely to become myopic. Worldwide population studies, some completed and some in progress, with a common protocol are gathering both genetic and environmental cohort data of great value. There have been rapid population changes in prevalence rates supporting an environmental influence. Interventions to prevent juvenile myopia progression include pharmacologic agents, glasses and contact lenses. Pharmacological interventions over 1-2 year trials have shown benefits. Peripheral vision defocus has been found to affect the emmetropization process and may be affected by wearing glasses or contacts. Accommodation accuracy also has been implicated in myopia progression. Further research will aim to assess both the role and interaction of environmental influences and genetic factors.

The evolution of primary progressive apraxia of speech.

Science.gov (United States)

Josephs, Keith A; Duffy, Joseph R; Strand, Edythe A; Machulda, Mary M; Senjem, Matthew L; Gunter, Jeffrey L; Schwarz, Christopher G; Reid, Robert I; Spychalla, Anthony J; Lowe, Val J; Jack, Clifford R; Whitwell, Jennifer L

2014-10-01

Primary progressive apraxia of speech is a recently described neurodegenerative disorder in which patients present with an isolated apraxia of speech and show focal degeneration of superior premotor cortex. Little is known about how these individuals progress over time, making it difficult to provide prognostic estimates. Thirteen subjects with primary progressive apraxia of speech underwent two serial comprehensive clinical and neuroimaging evaluations 2.4 years apart [median age of onset = 67 years (range: 49-76), seven females]. All underwent detailed speech and language, neurological and neuropsychological assessments, and magnetic resonance imaging, diffusion tensor imaging and (18)F-fluorodeoxyglucose positron emission tomography at both baseline and follow-up. Rates of change of whole brain, ventricle, and midbrain volumes were calculated using the boundary-shift integral and atlas-based parcellation, and rates of regional grey matter atrophy were assessed using tensor-based morphometry. White matter tract degeneration was assessed on diffusion-tensor imaging at each time-point. Patterns of hypometabolism were assessed at the single subject-level. Neuroimaging findings were compared with a cohort of 20 age, gender, and scan-interval matched healthy controls. All subjects developed extrapyramidal signs. In eight subjects the apraxia of speech remained the predominant feature. In the other five there was a striking progression of symptoms that had evolved into a progressive supranuclear palsy-like syndrome; they showed a combination of severe parkinsonism, near mutism, dysphagia with choking, vertical supranuclear gaze palsy or slowing, balance difficulties with falls and urinary incontinence, and one was wheelchair bound. Rates of whole brain atrophy (1.5% per year; controls = 0.4% per year), ventricular expansion (8.0% per year; controls = 3.3% per year) and midbrain atrophy (1.5% per year; controls = 0.1% per year) were elevated (P ≤ 0.001) in all 13

Geothermal progress monitor. Progress report No. 3, March-April 1980

Energy Technology Data Exchange (ETDEWEB)

1980-01-01

Progress is reviewed in the following areas: electric uses; direct heat uses; drilling activities; exploration; leases; outreach and technical assistance; feasibility studies and application demonstrations; geothermal loan guarantee program; general activities; R and D activities; legal, institutional, and regulatory activities; environmental activities; and state, local, and private sector activities. Also included are a list of reports and publications and a directory of individuals in the geothermal community. (MHR)

Tracking the Progress of English Language Learners

Science.gov (United States)

Murphy, Audrey F.

2009-01-01

Educators need to document progress for English language learners, and the best structures to put into place in order to record their growth. Beginning with the stages of language proficiency, student progress can be tracked through the use of a baseline in all four language strands and the creation of rubrics to monitor performance. Language…

Lactobacillus Decelerates Cervical Epithelial Cell Cycle Progression

Science.gov (United States)

Vielfort, Katarina; Weyler, Linda; Söderholm, Niklas; Engelbrecht, Mattias; Löfmark, Sonja; Aro, Helena

2013-01-01

We investigated cell cycle progression in epithelial cervical ME-180 cells during colonization of three different Lactobacillus species utilizing live cell microscopy, bromodeoxyuridine incorporation assays, and flow cytometry. The colonization of these ME-180 cells by L. rhamnosus and L. reuteri, originating from human gastric epithelia and saliva, respectively, was shown to reduce cell cycle progression and to cause host cells to accumulate in the G1 phase of the cell cycle. The G1 phase accumulation in L. rhamnosus-colonized cells was accompanied by the up-regulation and nuclear accumulation of p21. By contrast, the vaginal isolate L. crispatus did not affect cell cycle progression. Furthermore, both the supernatants from the lactic acid-producing L. rhamnosus colonies and lactic acid added to cell culture media were able to reduce the proliferation of ME-180 cells. In this study, we reveal the diversity of the Lactobacillus species to affect host cell cycle progression and demonstrate that L. rhamnosus and L. reuteri exert anti-proliferative effects on human cervical carcinoma cells. PMID:23675492

Lactobacillus decelerates cervical epithelial cell cycle progression.

Directory of Open Access Journals (Sweden)

Katarina Vielfort

Full Text Available We investigated cell cycle progression in epithelial cervical ME-180 cells during colonization of three different Lactobacillus species utilizing live cell microscopy, bromodeoxyuridine incorporation assays, and flow cytometry. The colonization of these ME-180 cells by L. rhamnosus and L. reuteri, originating from human gastric epithelia and saliva, respectively, was shown to reduce cell cycle progression and to cause host cells to accumulate in the G1 phase of the cell cycle. The G1 phase accumulation in L. rhamnosus-colonized cells was accompanied by the up-regulation and nuclear accumulation of p21. By contrast, the vaginal isolate L. crispatus did not affect cell cycle progression. Furthermore, both the supernatants from the lactic acid-producing L. rhamnosus colonies and lactic acid added to cell culture media were able to reduce the proliferation of ME-180 cells. In this study, we reveal the diversity of the Lactobacillus species to affect host cell cycle progression and demonstrate that L. rhamnosus and L. reuteri exert anti-proliferative effects on human cervical carcinoma cells.

Progress Report 1994; Rapport d`activite 1994

Energy Technology Data Exchange (ETDEWEB)

NONE

1995-12-31

This document is the 1994 annual progress report of the CEA-Direction of Waste Management (DGD). It comprises four chapters. The first chapter is a general presentation of radioactive wastes, of the management of liquid effluents, solid wastes, sealed sources, of the relations with the ANDRA (The French Agency for the Management of Radioactive Wastes), and of the research and development studies in progress for the improvement of waste management. The second chapter concerns the spent fuels and their reprocessing, in particular AGR and PWR type reactor fuels, the ``Caramel`` fuel from Osiris reactor and the cover elements from the Rapsodie reactor core. The long time storage of ancient fuels is also discussed. The third chapter concerns the dismantling of decommissioned installations, the actions in progress and the planning of dismantling actions up to the year 2000. Chapter four is devoted to the management of wastes from the Direction of Military Applications (DAM), the actions in progress in the different DAM centers and the cleansing projects at Marcoule plant. (J.S.). 5 figs., 28 tabs., 21 photos., 3 appendix.

Tracking the follow-up of work in progress papers.

Science.gov (United States)

Mubin, Omar; Arsalan, Mudassar; Al Mahmud, Abdullah

2018-01-01

Academic conferences offer numerous submission tracks to support the inclusion of a variety of researchers and topics. Work in progress papers are one such submission type where authors present preliminary results in a poster session. They have recently gained popularity in the area of Human Computer Interaction (HCI) as a relatively easier pathway to attending the conference due to their higher acceptance rate as compared to the main tracks. However, it is not clear if these work in progress papers are further extended or transitioned into more complete and thorough full papers or are simply one-off pieces of research. In order to answer this we explore self-citation patterns of four work in progress editions in two popular HCI conferences (CHI2010, CHI2011, HRI2010 and HRI2011). Our results show that almost 50% of the work in progress papers do not have any self-citations and approximately only half of the self-citations can be considered as true extensions of the original work in progress paper. Specific conferences dominate as the preferred venue where extensions of these work in progress papers are published. Furthermore, the rate of self-citations peaks in the immediate year after publication and gradually tails off. By tracing author publication records, we also delve into possible reasons of work in progress papers not being cited in follow up publications. In conclusion, we speculate on the main trends observed and what they may mean looking ahead for the work in progress track of premier HCI conferences.

Scales of Progress

Science.gov (United States)

Jung, Lee Ann

2018-01-01

What is Goal Attainment Scaling? In this article, Lee Ann Jung defines it as a way to measure a student's progress toward an individualized goal. Instead of measuring a skill at a set time (for instance, on a test or other assignment), Goal Attainment Scaling tracks the steps a student takes over the course of a year in a targeted skill. Together,…

Progress report 1982

International Nuclear Information System (INIS)

Paul, H.

1983-01-01

This progress report describes the scientific work and research results done by the institute for experimental physics, atom and nuclear physics of the Johannes-Kepler-Universitaet Linz in the period of 1982. The covered subject areas are ionization by cations, investigations of surface areas by light ions, measurement of stopping power in solids, data acquisition and aerosol physics. (A.N.)

Progress report 1981

International Nuclear Information System (INIS)

After giving a brief description of operations of an improvements to the University of Alberta nuclear physics facilities, this report summarizes the principal research programs. These include work on neutron scattering, thorium 232 fission, iodine 123 production. Progress towards the construction of MARIA, the Medical Accelerator Research Institute in Alberta, is described, and research on relativistic heavy ions is summarized

Systemic Inflammation in Progressive Multiple Sclerosis Involves Follicular T-Helper, Th17- and Activated B-Cells and Correlates with Progression

DEFF Research Database (Denmark)

Romme Christensen, Jeppe; Börnsen, Lars; Ratzer, Rikke

2013-01-01

with disease progression, using flow cytometry and gene expression analysis of CD4(+) and CD8(+)T-cells, B-cells, monocytes and dendritic cells. Furthermore, gene expression of cerebrospinal fluid cells was studied. Flow cytometry studies revealed increased frequencies of ICOS(+)TFH-cells in peripheral blood...... increased in PPMS and SPMS. In the analysis of B-cells, we found a significant increase of plasmablasts and DC-SIGN(+) and CD83(+)B-cells in SPMS. ICOS(+)TFH-cells and DC-SIGN(+)B-cells correlated with disease progression in SPMS patients. Gene expression analysis of peripheral blood cell subsets...... substantiated the flow cytometry findings by demonstrating increased expression of IL21, IL21R and ICOS in CD4(+)T-cells in progressive MS. Cerebrospinal fluid cells from RRMS and progressive MS (pooled SPMS and PPMS patients) had increased expression of TFH-cell and plasmablast markers. In conclusion...

Alkaptonuria is a novel human secondary amyloidogenic disease.

Science.gov (United States)

Millucci, Lia; Spreafico, Adriano; Tinti, Laura; Braconi, Daniela; Ghezzi, Lorenzo; Paccagnini, Eugenio; Bernardini, Giulia; Amato, Loredana; Laschi, Marcella; Selvi, Enrico; Galeazzi, Mauro; Mannoni, Alessandro; Benucci, Maurizio; Lupetti, Pietro; Chellini, Federico; Orlandini, Maurizio; Santucci, Annalisa

2012-11-01

Alkaptonuria (AKU) is an ultra-rare disease developed from the lack of homogentisic acid oxidase activity, causing homogentisic acid (HGA) accumulation that produces a HGA-melanin ochronotic pigment, of unknown composition. There is no therapy for AKU. Our aim was to verify if AKU implied a secondary amyloidosis. Congo Red, Thioflavin-T staining and TEM were performed to assess amyloid presence in AKU specimens (cartilage, synovia, periumbelical fat, salivary gland) and in HGA-treated human chondrocytes and cartilage. SAA and SAP deposition was examined using immunofluorescence and their levels were evaluated in the patients' plasma by ELISA. 2D electrophoresis was undertaken in AKU cells to evaluate the levels of proteins involved in amyloidogenesis. AKU osteoarticular tissues contained SAA-amyloid in 7/7 patients. Ochronotic pigment and amyloid co-localized in AKU osteoarticular tissues. SAA and SAP composition of the deposits assessed secondary type of amyloidosis. High levels of SAA and SAP were found in AKU patients' plasma. Systemic amyloidosis was assessed by Congo Red staining of patients' abdominal fat and salivary gland. AKU is the second pathology after Parkinson's disease where amyloid is associated with a form of melanin. Aberrant expression of proteins involved in amyloidogenesis has been found in AKU cells. Our findings on alkaptonuria as a novel type II AA amyloidosis open new important perspectives for its therapy, since methotrexate treatment proved to significantly reduce in vitro HGA-induced A-amyloid aggregates. Copyright © 2012 Elsevier B.V. All rights reserved.

Progress report of CJD

International Nuclear Information System (INIS)

2002-01-01

This paper is the progress report of the Russian Nuclear Data Center at F.E.I., Obninsk. Evaluations have been made for dosimetry reactions and neutron reactions. Analysis of the spectra and the production cross sections were made. (a.n.)

Progress report for '89

International Nuclear Information System (INIS)

Podest, M.

1990-08-01

The 1989 Progress Report presents the most important scientific and technical achievements of the Nuclear Research Institute's research work. Some specialized products prepared at or fabricated by the NRI are mentioned as well. (author). 24 figs., 8 tabs., 101 refs

Progress report for a research program in computational physics: Progress report, January 1, 1988-December 31, 1988

International Nuclear Information System (INIS)

Guralnik, G.S.

1988-01-01

The project of this progress report are all ultimately concerned with various aspects of numerical simulations of lattice gauge theories. These aspects include algorithms, machines, theoretical studies and actual simulations. We made progress in four general areas: studies of new algorithms, determination of the SU(3) β-function, studies of the finite temperature QCD phase transition in the presence of fermions, and the calculation of hadronic matrix elements. We will describe each of these in turn. 7 refs

Progressive supranuclear palsy syndrome induced by clebopride.

Science.gov (United States)

Campdelacreu, Jaume; Kumru, Hatice; Tolosa, Eduard; Valls-Solé, Josep; Benabarre, Antoni

2004-04-01

We report on a patient who presented with a progressive supranuclear palsy (PSP) syndrome while receiving clebopride (CLB), a prokinetic drug with central antidopaminergic properties. The clinical and neurophysiological signs progressively disappeared after CLB withdrawal. To our knowledge, this is the first published PSP-like syndrome attributable to an antidopaminergic drug. Copyright 2003 Movement Disorder Society

The spectrum of progressive derecho formation environments

Science.gov (United States)

Guastini, Corey T.

Progressive derechos are severe mesoscale convective systems that often form east of the Rocky Mountains during the warm season (May--August) and cause, by definition, straight-line wind damage along paths upwards of 400 km long. This study develops a subjective, seven-category classification scheme that spans the spectrum of progressive derecho formation environments from those dominated by robust upper-level ridges to those characterized by vigorous upper-level troughs. A climatology of 256 progressive derecho events is created for 1996--2013 and is categorized according to the developed classification scheme. Derecho initiation-relative composites are constructed for each of the seven groups using 0.5° Climate Forecast System Reanalysis data to document the environmental characteristics unique to each group as well as those shared among them. Finally, two in-depth case studies and five cursory case studies provide examples of the seven categories and reveal important nuances in mesoscale dynamic and thermodynamic structure inherent to all derecho cases. Results of the climatology show progressive derecho activity increases from 1 May through 1 July before decreasing again through the end of August and follows a northward trend in latitude from 1 May through 1 August before shifting slightly southward through the end of the warm season. Upslope flow in the vicinity of the Rocky Mountains initiates 28 percent of progressive derechos, upper-level troughs initiate 20 percent, 47 percent form in benign synoptic environments, and 5 percent are unclassifiable. Composite results show all progressive derecho initiation environments are marked by a long axis of instability caused by the overlap of high atmospheric moisture content and steep midlevel lapse rates, but the relative positions and strengths of upper-level troughs and ridges are crucial in determining how the instability axis develops and what its orientation in space will be. Case studies reveal instability

Validating predictors of disease progression in a large cohort of primary-progressive multiple sclerosis based on a systematic literature review.

Directory of Open Access Journals (Sweden)

Jan-Patrick Stellmann

Full Text Available New agents with neuroprotective or neuroregenerative potential might be explored in primary-progressive Multiple Sclerosis (PPMS--the MS disease course with leading neurodegenerative pathology. Identification of patients with a high short-term risk for progression may minimize study duration and sample size. Cohort studies reported several variables as predictors of EDSS disability progression but findings were partially contradictory.To analyse the impact of published predictors on EDSS disease progression in a large cohort of PPMS patients.A systematic literature research was performed to identify predictors for disease progression in PPMS. Individual case data from the Sylvia Lawry Centre (SLC and the Hamburg MS patient database (HAPIMS was pooled for a retrospective validation of these predictors on the annualized EDSS change.The systematic literature analysis revealed heterogeneous data from 3 prospective and 5 retrospective natural history cohort studies. Age at onset, gender, type of first symptoms and early EDSS changes were available for validation. Our pooled cohort of 597 PPMS patients (54% female had a mean follow-up of 4.4 years and mean change of EDSS of 0.35 per year based on 2503 EDSS assessments. There was no significant association between the investigated variables and the EDSS-change.None of the analysed variables were predictive for the disease progression measured by the annualized EDSS change. Whether PPMS is still unpredictable or our results may be due to limitations of cohort assessments or selection of predictors cannot be answered. Large systematic prospective studies with new endpoints are needed.

Journal of Biosciences | Indian Academy of Sciences

Indian Academy of Sciences (India)

Short peptides have been identified from amyloidogenic proteins that form amyloid fibrils in isolation. The hexapeptide stretch 21DIDLHL26 has been shown to be important in the self-assembly of the Src homology 3 (SH3) domain of p85 subunit of bovine phosphatidylinositol-3-kinase (PI3-SH3). The SH3 domain of ...

Controlling myopia progression in children and adolescents

Directory of Open Access Journals (Sweden)

Smith MJ

2015-08-01

Full Text Available Molly J Smith, Jeffrey J WallineThe Ohio State University College of Optometry, Columbus, OH, USAAbstract: Myopia is a common disorder, affecting approximately one-third of the US population and over 90% of the population in some East Asian countries. High amounts of myopia are associated with an increased risk of sight-threatening problems, such as retinal detachment, choroidal degeneration, cataracts, and glaucoma. Slowing the progression of myopia could potentially benefit millions of children in the USA. To date, few strategies used for myopia control have proven to be effective. Treatment options such as undercorrection of myopia, gas permeable contact lenses, and bifocal or multifocal spectacles have all been proven to be ineffective for myopia control, although one recent randomized clinical trial using executive top bifocal spectacles on children with progressive myopia has shown to decrease the progression to nearly half of the control subjects. The most effective methods are the use of orthokeratology contact lenses, soft bifocal contact lenses, and topical pharmaceutical agents such as atropine or pirenzepine. Although none of these modalities are US Food and Drug Administration-approved to slow myopia progression, they have been shown to slow the progression by approximately 50% with few risks. Both orthokeratology and soft bifocal contact lenses have shown to slow myopia progression by slightly less than 50% in most studies. Parents and eye care practitioners should work together to determine which modality may be best suited for a particular child. Topical pharmaceutical agents such as anti-muscarinic eye drops typically lead to light sensitivity and poor near vision. The most effective myopia control is provided by atropine, but is rarely prescribed due to the side effects. Pirenzepine provides myopia control with little light sensitivity and few near-vision problems, but it is not yet commercially available as an eye drop or

Exercise capacity and progression from prehypertension to hypertension.

Science.gov (United States)

Faselis, Charles; Doumas, Michael; Kokkinos, John Peter; Panagiotakos, Demosthenes; Kheirbek, Raya; Sheriff, Helen M; Hare, Katherine; Papademetriou, Vasilios; Fletcher, Ross; Kokkinos, Peter

2012-08-01

Prehypertension is likely to progress to hypertension. The rate of progression is determined mostly by age and resting blood pressure but may also be attenuated by increased fitness. A graded exercise test was performed in 2303 men with prehypertension at the Veterans Affairs Medical Centers in Washington, DC. Four fitness categories were defined, based on peak metabolic equivalents (METs) achieved. We assessed the association between exercise capacity and rate of progression to hypertension (HTN). The median follow-up period was 7.8 years (mean (± SD) 9.2±6.1 years). The incidence rate of progression from prehypertension to hypertension was 34.4 per 1000 person-years. Exercise capacity was a strong and independent predictor of the rate of progression. Compared to the High-Fit individuals (>10.0 METs), the adjusted risk for developing HTN was 66% higher (hazard ratio, 1.66; 95% CI, 1.2 to 2.2; P=0.001) for the Low-Fit and, similarly, 72% higher (hazard ratio, 1.72; 95% CI, 1.2 to 2.3; P=0.001) for the Least-Fit individuals, whereas it was only 36% for the Moderate-Fit (hazard ratio, 1.36; 95% CI, 0.99 to 1.80; P=0.056). Significant predictors for the progression to HTN were also age (19% per 10 years), resting systolic blood pressure (16% per 10 mm Hg), body mass index (15.3% per 5 U), and type 2 diabetes mellitus (2-fold). In conclusion, an inverse, S-shaped association was shown between exercise capacity and the rate of progression from prehypertension to hypertension in middle-aged and older male veterans. The protective effects of fitness were evident when exercise capacity exceeded 8.5 METs. These findings emphasize the importance of fitness in the prevention of hypertension.

Structural MRI correlates of amyotrophic lateral sclerosis progression.

Science.gov (United States)

Senda, Joe; Atsuta, Naoki; Watanabe, Hirohisa; Bagarinao, Epifanio; Imai, Kazunori; Yokoi, Daichi; Riku, Yuichi; Masuda, Michihito; Nakamura, Ryoichi; Watanabe, Hazuki; Ito, Mizuki; Katsuno, Masahisa; Naganawa, Shinji; Sobue, Gen

2017-11-01

Amyotrophic lateral sclerosis (ALS) presents with varying degrees of brain degeneration that can extend beyond the corticospinal tract (CST). Furthermore, the clinical course and progression of ALS varies widely. Brain degeneration detected using structural MRI could reflect disease progression. On study registration, 3-Tesla volumetric MRI and diffusion tensor imaging scans were obtained at baseline in 38 healthy controls and 67 patients with sporadic ALS. Patients had Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) scores of ≥36 and did not have the chromosome 9, open reading frame 72 repeat expansion. Six months later, changes in ALSFRS-R (ΔALSFRS-R) scores were calculated and patients were grouped into three categories, namely, patients with slow progression with ΔALSFRS-R scores ≤3 (n=19), intermediate progression with ΔALSFRS-R scores =4, 5 and 6 (n=36) and rapid progression with ΔALSFRS-R scores ≥7 (n=12). We analysed voxel-based morphometry and tract-based spatial statistics among these subgroups and controls. In comparison with controls, patients with ALS showed grey matter atrophy and decreased fractional anisotropy beyond the motor cortex and CST, especially in the frontotemporal lobes and basal ganglia. Moreover, the degree of change was highly proportional to ΔALSFRS-R at the 6-month assessment. A more rapid disease progression and poorer functional decline were associated with greater involvement of the extra-motor cortex and basal ganglia, suggesting that the spatial extent of brain involvement can be an indicator of the progression in ALS. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Annual progress report

International Nuclear Information System (INIS)

Russek, A.

1975-06-01

Progress has been made in calculation of cross-sections for dielectronic and radiative recombination when hot electrons are incident on partially stripped impurity ions. Calculations were completed for the cases of 1 keV and 10 keV electrons incident on ions of arbitrary Z with ionization state consistent with a 1 keV plasma temperature. It was found that dielectronic recombination dominates radiative recombination by a factor of 100 at 1 keV incident electron energy to a factor of 1000 at 10 keV incident electron energy. The work is now being extended to other plasma temperatures and is being improved by more accurate calculation of the matrix elements involved. Progress was also made in the calculation of accurate bremsstrahlung and higher order radiative processes which also occur when hot electrons are incident on partially stripped impurity ions. Formal expressions for the matrix elements have been obtained for cross-sections in a fully relativistic partial wave analysis for bremsstrahlung radiation both with and without electron excitation of the target ion. Final evaluation now awaits the evaluation of the relativistic radial integrals involved in these matrix elements. (U.S.)

Progressive nature of heart failure and systems biology

Directory of Open Access Journals (Sweden)

George E. Louridas

2015-01-01

Full Text Available The progressive nature of heart failure (HF is the predominant cause for the clinical course that the HF syndrome is taking. Systems biology methodology is of the utmost importance to explain and comprehend the built-in mechanisms of adverse clinical progression. Various heart diseases produce myocardial damage with subsequent left ventricular remodeling which is the principal underlying pathophysiological mechanism for the clinical progression of HF. The self-organized positive feedback stabilization mechanisms of left ventricular remodeling, adrenergic stimulation and activation of the renin-angiotensin-aldosterone system and natriuretic peptide systems, are hierarchical adaptive processes. These adaptive processes are responsible for further left ventricular remodeling with subsequent clinical deterioration and for the emergence of clinical phenotypes. These mechanisms are counteracted with angiotensin-converting enzyme inhibitors, angiotensin receptor blockers and β-blockers in an attempt to improve the adverse clinical phenomena of HF progression in a new but clinically worse stabilization level. In this review our intention is to underline the progressive nature of the HF syndrome and to demonstrate the significance of ventricular remodeling and the role of self-organized positive feedback adaptive processes.

Are Forecast Updates Progressive?

NARCIS (Netherlands)

C-L. Chang (Chia-Lin); Ph.H.B.F. Franses (Philip Hans); M.J. McAleer (Michael)

2010-01-01

textabstractMacro-economic forecasts typically involve both a model component, which is replicable, as well as intuition, which is non-replicable. Intuition is expert knowledge possessed by a forecaster. If forecast updates are progressive, forecast updates should become more accurate, on average,

Progressive neuronal degeneration of childhood with liver disease

International Nuclear Information System (INIS)

Kendall, B.E.; Boyd, S.G.; Egger, J.; Harding, B.N.

1987-01-01

The clinical, electrophysiological and neuroradiological features of thirteen patients suffering from progressive neuronal degeneration of childhood with liver failure are presented. The disease commonly presents very early in life with progressive mental retardation, followed by intractable epilepsy, and should be suspected clinically especially if there is a family history of similar disorder in a sibling. On computed tomography there are low density regions, particularly in the occipital and posterior temporal lobes, involving both cortex and white matter, combined with or followed by progressive atrophy. Typical EEG findings may be confirmatory. (orig.)

Progressive pseudorheumatoid dysplasia in North and West Africa ...

African Journals Online (AJOL)

Progressive pseudorheumatoid dysplasia is a rare autosomal recessive spondyloepiphyseal dysplasia characterized by predominant involvement of articular cartilage with progressive joint stiffness and enlargement in the absence of inflammation. Short stature, joint contractures, gait disturbance, and scoliosis and/or ...

Progression of Stargardt Disease as Determined by Fundus Autofluorescence in the Retrospective Progression of Stargardt Disease Study (ProgStar Report No. 9).

Science.gov (United States)

Strauss, Rupert W; Muñoz, Beatriz; Ho, Alexander; Jha, Anamika; Michaelides, Michel; Cideciyan, Artur V; Audo, Isabelle; Birch, David G; Hariri, Amir H; Nittala, Muneeswar G; Sadda, SriniVas; West, Sheila; Scholl, Hendrik P N

2017-11-01

Sensitive outcome measures for disease progression are needed for treatment trials of Stargardt disease. To describe the yearly progression rate of atrophic lesions in the retrospective Progression of Stargardt Disease study. A multicenter retrospective cohort study was conducted at tertiary referral centers in the United States and Europe. A total of 251 patients aged 6 years or older at baseline, harboring disease-causing variants in ABCA4 (OMIM 601691), enrolled in the study from 9 centers between August 2, 2013, and December 12, 2014; of these patients, 215 had at least 2 gradable fundus autofluorescence images with atrophic lesion(s) present in at least 1 eye. Areas of definitely decreased autofluorescence (DDAF) and questionably decreased autofluorescence were quantified by a reading center. Progression rates were estimated from linear mixed models with time as the independent variable. Yearly rate of progression using the growth of atrophic lesions measured by fundus autofluorescence. A total of 251 participants (458 study eyes) were enrolled. Images from 386 eyes of 215 participants (126 females and 89 males; mean [SD] age, 29.9 [14.7] years; mean [SD] age of onset of symptoms, 21.9 [13.3] years) showed atrophic lesions present on at least 2 visits and were graded for 2 (156 eyes), 3 (174 eyes), or 4 (57 eyes) visits. A subset of 224 eyes (123 female participants and 101 male participants; mean [SD] age, 33.0 [15.1] years) had areas of DDAF present on at least 2 visits; these eyes were included in the estimation of the progression of the area of DDAF. At the first visit, DDAF was present in 224 eyes (58.0%), with a mean (SD) lesion size of 2.2 (2.7) mm2. The total mean (SD) area of decreased autofluorescence (DDAF and questionably decreased autofluorescence) at first visit was 2.6 (2.8) mm2. Mean progression of DDAF was 0.51 mm2/y (95% CI, 0.42-0.61 mm2/y), and of total decreased fundus autofluorescence was 0.35 mm2/y (95% CI, 0.28-0.43 mm2/y). Rates of

Progressive taxation and the subjective well-being of nations.

Science.gov (United States)

Oishi, Shigehiro; Schimmack, Ulrich; Diener, Ed

2012-01-01

Using data from the Gallup World Poll, we examined whether progressive taxation is associated with increased levels of subjective well-being. Consistent with Rawls's theory of justice, our results showed that progressive taxation was positively associated with the subjective well-being of nations. However, the overall tax rate and government spending were not associated with the subjective well-being of nations. Furthermore, controlling for the wealth of nations and income inequality, we found that respondents living in a nation with more-progressive taxation evaluated their lives as closer to the best possible life and reported having more positive and less negative daily experiences than did respondents living in a nation with less-progressive taxation. Finally, we found that the association between more-progressive taxation and higher levels of subjective well-being was mediated by citizens' satisfaction with public goods, such as education and public transportation.

Communication of nuclear data progress

International Nuclear Information System (INIS)

2006-07-01

This is the 30th issue of Communication of Nuclear Data Progress (CNDP), in which the progress and achievements in nuclear data field in China during 2004 are carried. It includes the evaluations and model calculations of neutron data for n+ 31 P, 59 Co, 92-106 Mo, Nat-116 Cd, 233 U and the covariance data evaluation of experimental data for 27 Al, update the decay data for radionuclide 7 Be. Some results of studies for nuclear evaluation tool and model are also included in this issue, i.e. reaction mechanism studies of 5 He, a new method of evaluating the discrepant data, linear fit of correlative data by least squared method et al. (authors)

[Progress in stem cells and regenerative medicine].

Science.gov (United States)

Wang, Libin; Zhu, He; Hao, Jie; Zhou, Qi

2015-06-01

Stem cells have the ability to differentiate into all types of cells in the body and therefore have great application potential in regenerative medicine, in vitro disease modelling and drug screening. In recent years, stem cell technology has made great progress, and induced pluripotent stem cell technology revolutionizes the whole stem cell field. At the same time, stem cell research in our country has also achieved great progress and becomes an indispensable power in the worldwide stem cell research field. This review mainly focuses on the research progress in stem cells and regenerative medicine in our country since the advent of induced pluripotent stem cell technology, including induced pluripotent stem cells, transdifferentiation, haploid stem cells, and new gene editing tools.

The natural history of primary progressive multiple sclerosis

NARCIS (Netherlands)

Koch, Marcus; Kingwell, Elaine; Rieckmann, Peter; Tremlett, Helen

2009-01-01

Background: Primary progressive multiple sclerosis (PPMS) carries the worst prognosis of the multiple sclerosis (MS) subtypes and is currently untreatable. A previous analysis of the British Columbia MS database challenged the view that disability progression is rapid in PPMS, but identified few

Nonlinear Progressive Collapse Analysis Including Distributed Plasticity

Directory of Open Access Journals (Sweden)

Mohamed Osama Ahmed

2016-01-01

Full Text Available This paper demonstrates the effect of incorporating distributed plasticity in nonlinear analytical models used to assess the potential for progressive collapse of steel framed regular building structures. Emphasis on this paper is on the deformation response under the notionally removed column, in a typical Alternate Path (AP method. The AP method employed in this paper is based on the provisions of the Unified Facilities Criteria – Design of Buildings to Resist Progressive Collapse, developed and updated by the U.S. Department of Defense [1]. The AP method is often used for to assess the potential for progressive collapse of building structures that fall under Occupancy Category III or IV. A case study steel building is used to examine the effect of incorporating distributed plasticity, where moment frames were used on perimeter as well as the interior of the three dimensional structural system. It is concluded that the use of moment resisting frames within the structural system will enhance resistance to progressive collapse through ductile deformation response and that it is conserative to ignore the effects of distributed plasticity in determining peak displacement response under the notionally removed column.

Progressive multiple sequence alignments from triplets

Directory of Open Access Journals (Sweden)

Stadler Peter F

2007-07-01

Full Text Available Abstract Background The quality of progressive sequence alignments strongly depends on the accuracy of the individual pairwise alignment steps since gaps that are introduced at one step cannot be removed at later aggregation steps. Adjacent insertions and deletions necessarily appear in arbitrary order in pairwise alignments and hence form an unavoidable source of errors. Research Here we present a modified variant of progressive sequence alignments that addresses both issues. Instead of pairwise alignments we use exact dynamic programming to align sequence or profile triples. This avoids a large fractions of the ambiguities arising in pairwise alignments. In the subsequent aggregation steps we follow the logic of the Neighbor-Net algorithm, which constructs a phylogenetic network by step-wisely replacing triples by pairs instead of combining pairs to singletons. To this end the three-way alignments are subdivided into two partial alignments, at which stage all-gap columns are naturally removed. This alleviates the "once a gap, always a gap" problem of progressive alignment procedures. Conclusion The three-way Neighbor-Net based alignment program aln3nn is shown to compare favorably on both protein sequences and nucleic acids sequences to other progressive alignment tools. In the latter case one easily can include scoring terms that consider secondary structure features. Overall, the quality of resulting alignments in general exceeds that of clustalw or other multiple alignments tools even though our software does not included heuristics for context dependent (mismatch scores.

Quarterly Progress Report (January 1 to March 31, 1950)

Energy Technology Data Exchange (ETDEWEB)

Brookhaven National Laboratory

1950-04-01

This is the first of a series of Quarterly Reports. These reports will deal primarily with the progress made in our scientific program during a three months period. Those interested in matters pertaining to organization, administration, complete scientific program, personnel and other matters not directly involved in current scientific progress are referred to our Annual Progress Report which is issued in January. We have attempted to describe new information that appears significant, or of interest, to other scientists within the Atomic Energy Commission Laboratories. No effort has been made, however, to detail progress in each and every research project. Little or no reference will therefore be found to the projects in which progress during the current period is considered too inconclusive. Since our organizational structure is departmental, the work described herein is arranged in the following sequence: (1) Accelerator Project; (2) Biology Department; (3) Chemistry Department; (4) Instrumentation and Health Physic8 Department; (5) Medical Department; (6) Physics Department; and (7) Reactor Science and Engineering Department.

Geothermal Progress Monitor report No. 5. Progress report, June 1981

Energy Technology Data Exchange (ETDEWEB)

1981-01-01

Updated information is presented on activities and progress in the areas of electric power plants, direct heat applications, deep well drilling, leasing of federal lands, legislative and regulatory actions, research and development, and others. Special attention is given in this report to 1980 highlights, particularly in the areas of electric and direct heat uses, drilling, and the Federal lands leasing program. This report also includes a summary of the DOE FY 1982 geothermal budget request to Congress.

Small things matter: Implications of APP intracellular domain AICD nuclear signaling in the progression and pathogenesis of Alzheimer's disease.

Science.gov (United States)

Bukhari, Hassan; Glotzbach, Annika; Kolbe, Katharina; Leonhardt, Gregor; Loosse, Christina; Müller, Thorsten

2017-09-01

Alzheimer's disease (AD) is the most common neurodegenerative disease with tens of millions of people affected worldwide. The pathogenesis is still poorly understood and various therapeutical approaches targeting the amyloid β (Aβ) peptide, a product of the amyloidogenic cleavage of the amyloid precursor protein (APP), failed. Moreover, a couple of studies critically questioned the relevance of Aβ in the pathogenesis of AD. Thus, new ideas need to be studied and one highly interesting hypothesis is the APP mediated signal transduction to the nucleus. As a consequence nuclear -potentially toxic- structures emerge, which were recently found to a high extent in human AD tissue and thus, may contribute to neurodegeneration. Relevant for the signaling machinery are modifications at the very C-terminal end of the precursor protein, the APP intracellular domain (AICD). In this review we update the knowledge on mechanisms on AICD referring to our 2008 article: The amyloid precursor protein intracellular domain (AICD) as modulator of gene expression, apoptosis, and cytoskeletal dynamics-Relevance for Alzheimer's disease (T. Muller, et al., 2008). We summarize how AICD is generated and degraded, we describe its intramolecular motifs, translational modifications, and how those as well as APP dimerization influence AICD generation and function. Moreover, we resume the AICD interactome and elucidate AICDs involvement in nuclear signaling, transcriptional regulation, cell death, DNA repair and cell cycle re-entry and we give insights in its physiological function. Results are summarized in the comprehensive poster "The world of AICD". Copyright © 2017 Elsevier Ltd. All rights reserved.

Progress in surface and membrane science

CERN Document Server

Danielli, J F; Cadenhead, D A

1973-01-01

Progress in Surface and Membrane Science, Volume 6 covers the developments in the study of surface and membrane science. The book discusses the progress in surface and membrane science; the solid state chemistry of the silver halide surface; and the experimental and theoretical aspects of the double layer at the mercury-solution interface. The text also describes contact-angle hysteresis; ion binding and ion transport produced by neutral lipid-soluble molecules; and the biophysical interactions of blood proteins with polymeric and artificial surfaces. Physical chemists, biophysicists, and phys

Geothermal progress monitor report No. 6

Energy Technology Data Exchange (ETDEWEB)

1982-06-01

Geothermal Progress Monitor Report No. 6 presents a state-by-state summary of the status of geothermal leasing, exploration, and development in major physiographic regions where geothermal resource potential has been identified. Recent state-specific activities are reported at the end of each state status report, while recent activities of a more general nature are summarized briefly in Part II of the report. A list of recent publications of potential interest to the geothermal community and a directory of contributors to the geothermal progress monitoring system are also included.

Recent Progress in Large-Scale Structure

CERN Multimedia

CERN. Geneva

2014-01-01

I will discuss recent progress in the understanding of how to model galaxy clustering. While recent analyses have focussed on the baryon acoustic oscillations as a probe of cosmology, galaxy redshift surveys contain a lot more information than the acoustic scale. In extracting this additional information three main issues need to be well understood: nonlinear evolution of matter fluctuations, galaxy bias and redshift-space distortions. I will present recent progress in modeling these three effects that pave the way to constraining cosmology and galaxy formation with increased precision.

Response: Progress Takes Time.

Science.gov (United States)

Rist, Marilee C.

1984-01-01

Although declining enrollment and administrative seniority have hampered efforts to eliminate sex discrimination in employment practices in three Long Island, New York, school systems (Commack, Smithtown, and Bay Shore), progress is being made. Because of the Reagan administration's lack of support for affirmative action, however, litigation…

Progressive osseous heteroplasia (POH): an Egyptian patient | El ...

African Journals Online (AJOL)

Progressive osseous heteroplasia is a rare genetic disorder characterized by cutaneous ossification during infancy and progressive ossification of subcutaneous and deep connective tissue including muscle and fascia during childhood. It is at the severe end of a spectrum of Guanine Nucleotide-binding protein, ...

Risk-taking under progressive taxation

OpenAIRE

Bamberg, Günter

1988-01-01

Risk-taking under progressive taxation : 3 partial effects / Günter Bamberg ; Wolfram R. Richter. - In: Measurement in economics / ed. by Wolfgang Eichhorn. - Heidelberg : Physica-Verl., 1988. - S. 479-497

High-dose erythropoietin in patients with progressive multiple sclerosis

DEFF Research Database (Denmark)

Schreiber, Karen; Magyari, Melinda; Sellebjerg, Finn

2017-01-01

BACKGROUND: Erythropoietin (EPO) is a part of an endogenous neuroprotective system in the brain and may address pathophysiological mechanisms in progressive multiple sclerosis (MS). OBJECTIVE: To evaluate a treatment effect of EPO on progressive MS. METHODS: This was a single-center, randomized......, double-blind, placebo-controlled phase 2 trial, in which 52 patients with secondary or primary progressive MS were allocated to treatment with recombinant EPO (48,000 IU) or placebo, administered intravenously 17 times during 24 weeks. Patients had an Expanded Disability Status Score (EDSS) from 4 to 6......: This study provides class II evidence that treatment with high-dose EPO is not an effective treatment in patients with moderately advanced progressive MS....

Ghrelin and cancer progression.

Science.gov (United States)

Lin, Tsung-Chieh; Hsiao, Michael

2017-08-01

Ghrelin is a small peptide with 28 amino acids, and has been characterized as the ligand of the growth hormone secretagogue receptor (GHSR). In addition to its original function in stimulating pituitary growth hormone release, ghrelin is multifunctional and plays a role in the regulation of energy balance, gastric acid release, appetite, insulin secretion, gastric motility and the turnover of gastric and intestinal mucosa. The discovery of ghrelin and GHSR expression beyond normal tissues suggests its role other than physiological function. Emerging evidences have revealed ghrelin's function in regulating several processes related to cancer progression, especially in metastasis and proliferation. We further show the relative GHRL and GHSR expression in pan-cancers from The Cancer Genome Atlas (TCGA), suggesting the potential pathological role of the axis in cancers. This review focuses on ghrelin's biological function in cancer progression, and reveals its clinical significance especially the impact on cancer patient outcome. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Factors Affecting Career Progress of MBA Students

Directory of Open Access Journals (Sweden)

Vivien T. Supangco

2001-06-01

Full Text Available This paper explored the factors that affect career progress of students in the MBA program of the University of the Philippines.To understand career progression, four measures of career progress were used in this study, namely: number of promotions, number of years in between promotions, total cash compensation, and number of administrative levels from the company president. On the other hand, the factors used to explain career progess included human capital, organizational, interpersonal and demographic variables.The results showed that the different measures of career progress had distinct determinants implying different dynamics. It appeared that measures of career progress that are sensitive to the value employers attach to the individual (Whitely, Dougherty, & Dreher, 1991 such as total compensation, total number of promotion and years per promotion were related with human capital factors such as work experience and number of companies worked for. On the other hand, measures that relate to centrality if the position, in which market forces have less impact, were associated with organizational variables such as organization size and the demographic variable gender.While gender did not explain variation in total compensation, number of promotions and number of uears between promotions, these null results are important for two reasons. First, it implies that the female MBA students were at par with their male counterparts as fas as these measures of career progress are concerned. Second, it challenges the generalizability of the finding of gender segregation at the organizational level-where men receive significantly higher wages that women-which is a common finding among studies done in the United States. The results using the MBA students as sample show that income and promotion parity may indeed be achievable and this brings hope to women in general.However, the statistical significance of gender in explaining career progress as centrality

Content layer progressive coding of digital maps

DEFF Research Database (Denmark)

Forchhammer, Søren; Jensen, Ole Riis

2000-01-01

A new lossless context based method is presented for content progressive coding of limited bits/pixel images, such as maps, company logos, etc., common on the WWW. Progressive encoding is achieved by separating the image into content layers based on other predefined information. Information from...... already coded layers are used when coding subsequent layers. This approach is combined with efficient template based context bi-level coding, context collapsing methods for multi-level images and arithmetic coding. Relative pixel patterns are used to collapse contexts. The number of contexts are analyzed....... The new methods outperform existing coding schemes coding digital maps and in addition provide progressive coding. Compared to the state-of-the-art PWC coder, the compressed size is reduced to 60-70% on our layered test images....

Content Layer progressive Coding of Digital Maps

DEFF Research Database (Denmark)

Forchhammer, Søren; Jensen, Ole Riis

2002-01-01

A new lossless context based method is presented for content progressive coding of limited bits/pixel images, such as maps, company logos, etc., common on the World Wide Web. Progressive encoding is achieved by encoding the image in content layers based on color level or other predefined...... information. Information from already coded layers are used when coding subsequent layers. This approach is combined with efficient template based context bilevel coding, context collapsing methods for multilevel images and arithmetic coding. Relative pixel patterns are used to collapse contexts. Expressions...... for calculating the resulting number of contexts are given. The new methods outperform existing schemes coding digital maps and in addition provide progressive coding. Compared to the state-of-the-art PWC coder, the compressed size is reduced to 50-70% on our layered map test images....

Quantitative Reasoning in Environmental Science: A Learning Progression

Science.gov (United States)

Mayes, Robert Lee; Forrester, Jennifer Harris; Christus, Jennifer Schuttlefield; Peterson, Franziska Isabel; Bonilla, Rachel; Yestness, Nissa

2014-01-01

The ability of middle and high school students to reason quantitatively within the context of environmental science was investigated. A quantitative reasoning (QR) learning progression was created with three progress variables: quantification act, quantitative interpretation, and quantitative modeling. An iterative research design was used as it…

Communication of nuclear data progress

Energy Technology Data Exchange (ETDEWEB)

NONE

2006-07-15

This is the 30th issue of Communication of Nuclear Data Progress (CNDP), in which the progress and achievements in nuclear data field in China during 2004 are carried. It includes the evaluations and model calculations of neutron data for n+{sup 31}P, {sup 59}Co, {sup 92-106}Mo, {sup Nat-116}Cd, {sup 233}U and the covariance data evaluation of experimental data for {sup 27}Al, update the decay data for radionuclide {sup 7}Be. Some results of studies for nuclear evaluation tool and model are also included in this issue, i.e. reaction mechanism studies of {sup 5}He, a new method of evaluating the discrepant data, linear fit of correlative data by least squared method et al. (authors)

Frontotemporal dementia and primary progressive aphasia, a review

Directory of Open Access Journals (Sweden)

Kirshner HS

2014-06-01

Full Text Available Howard S KirshnerDepartment of Neurology, Vanderbilt University Medical Center, Nashville, TN, USAAbstract: Frontotemporal dementias are neurodegenerative diseases in which symptoms of frontal and/or temporal lobe disease are the first signs of the illness, and as the diseases progress, they resemble a focal left hemisphere process such as stroke or traumatic brain injury, even more than a neurodegenerative disease. Over time, some patients develop a more generalized dementia. Four clinical subtypes characterize the predominant presentations of this illness: behavioral or frontal variant FTD, progressive nonfluent aphasia, semantic dementia, and logopenic primary progressive aphasia. These clinical variants correlate with regional patterns of atrophy on brain imaging studies such as MRI and PET scanning, as well as with biochemical and molecular genetic variants of the disorder. The treatment is as yet only symptomatic, but advances in molecular genetics promise new therapies.Keywords: FTD, behavior variant or frontal variant FTD, pick's disease, PPA, progressive nonfluent aphasia

Nitrate | Cancer Trends Progress Report

Science.gov (United States)

The Cancer Trends Progress Report, first issued in 2001, summarizes our nation's advances against cancer in relation to Healthy People targets set forth by the Department of Health and Human Services.

Sunburn | Cancer Trends Progress Report

Science.gov (United States)

The Cancer Trends Progress Report, first issued in 2001, summarizes our nation's advances against cancer in relation to Healthy People targets set forth by the Department of Health and Human Services.

Technical progress and its strategic consequences

International Nuclear Information System (INIS)

Bouchard, G.

1999-01-01

The history of energy during recent decades has shown that technical progress can have consequences for the organisation of markets, company strategies and the economy in general, confounding all forecasts and going beyond simple technical change. As a consequence for example, improvements in the techniques concerning the exploration and production of hydrocarbons have led to the petrol 'counter-crisis', the reduction in the power of OPEC and undreamed of gains in wealth for certain countries. The progress in gas turbines has led to the reversal of the age-old tendency towards increases in the size of electricity production units and encouraged the liberation of this sector. When looking at the future it is therefore judicious to try and understand the forces at work, and the major trends which result. This is the aim of the articles in this edition of the Revue de l'Energie, published on the occasion of the European colloquium on 'Technical progress faced with the challenges of the energy sector in the future' organised by the Association of Energy Economists. (authors)

Neuroimaging classification of progression patterns in glioblastoma: a systematic review.

Science.gov (United States)

Piper, Rory J; Senthil, Keerthi K; Yan, Jiun-Lin; Price, Stephen J

2018-03-30

Our primary objective was to report the current neuroimaging classification systems of spatial patterns of progression in glioblastoma. In addition, we aimed to report the terminology used to describe 'progression' and to assess the compliance with the Response Assessment in Neuro-Oncology (RANO) Criteria. We conducted a systematic review to identify all neuroimaging studies of glioblastoma that have employed a categorical classification system of spatial progression patterns. Our review was registered with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) registry. From the included 157 results, we identified 129 studies that used labels of spatial progression patterns that were not based on radiation volumes (Group 1) and 50 studies that used labels that were based on radiation volumes (Group 2). In Group 1, we found 113 individual labels and the most frequent were: local/localised (58%), distant/distal (51%), diffuse (20%), multifocal (15%) and subependymal/subventricular zone (15%). We identified 13 different labels used to refer to 'progression', of which the most frequent were 'recurrence' (99%) and 'progression' (92%). We identified that 37% (n = 33/90) of the studies published following the release of the RANO classification were adherent compliant with the RANO criteria. Our review reports significant heterogeneity in the published systems used to classify glioblastoma spatial progression patterns. Standardization of terminology and classification systems used in studying progression would increase the efficiency of our research in our attempts to more successfully treat glioblastoma.

Temporal acoustic measures distinguish primary progressive apraxia of speech from primary progressive aphasia.

Science.gov (United States)

Duffy, Joseph R; Hanley, Holly; Utianski, Rene; Clark, Heather; Strand, Edythe; Josephs, Keith A; Whitwell, Jennifer L

2017-05-01

The purpose of this study was to determine if acoustic measures of duration and syllable rate during word and sentence repetition, and a measure of within-word lexical stress, distinguish speakers with primary progressive apraxia of speech (PPAOS) from nonapraxic speakers with the agrammatic or logopenic variants of primary progressive aphasia (PPA), and control speakers. Results revealed that the PPAOS group had longer durations and reduced rate of syllable production for most words and sentences, and the measure of lexical stress. Sensitivity and specificity indices for the PPAOS versus the other groups were highest for longer multisyllabic words and sentences. For the PPAOS group, correlations between acoustic measures and perceptual ratings of AOS were moderately high to high. Several temporal measures used in this study may aid differential diagnosis and help quantify features of PPAOS that are distinct from those associated with PPA in which AOS is not present. Copyright © 2017 Elsevier Inc. All rights reserved.

Progranulin-Associated Primary Progressive Aphasia: A Distinct Phenotype?

Science.gov (United States)

Rohrer, Jonathan D.; Crutch, Sebastian J.; Warrington, Elizabeth K.; Warren, Jason D.

2010-01-01

The neuropsychological features of the primary progressive aphasia (PPA) syndromes continue to be defined. Here we describe a detailed neuropsychological case study of a patient with a mutation in the progranulin ("GRN") gene who presented with progressive word-finding difficulty. Key neuropsychological features in this case included gravely…

Decision-Making Accuracy of CBM Progress-Monitoring Data

Science.gov (United States)

Hintze, John M.; Wells, Craig S.; Marcotte, Amanda M.; Solomon, Benjamin G.

2018-01-01

This study examined the diagnostic accuracy associated with decision making as is typically conducted with curriculum-based measurement (CBM) approaches to progress monitoring. Using previously published estimates of the standard errors of estimate associated with CBM, 20,000 progress-monitoring data sets were simulated to model student reading…

Factors Associated With Progression Of Diabetic Retinopathy, A ...

African Journals Online (AJOL)

Background: Diabetic retinopathy (DR) is a progressive sight threatening diabetic complication. The prognosis seems to be related to largely modifiable risk factors. Objectives: The aim of the study was to identify factors that could be associated with progression of DR. among adult diabetic patients attending primary health ...

Progresses in proton radioactivity studies

Energy Technology Data Exchange (ETDEWEB)

Ferreira, L. S., E-mail: flidia@ist.utl.pt [Center of Physics and Engineering of Advanced Materials, CeFEMA and Departamento de Física, Instituto Superior Técnico, Universidade de Lisboa, Avenida Rovisco Pais, P1049-001 Lisbon (Portugal); Maglione, E. [Dipartimento di Fisica e Astronomia “G. Galilei”, Via Marzolo 8, I-35131 Padova, Italy and Istituto Nazionale di Fisica Nucleare, Padova (Italy)

2016-07-07

In the present talk, we will discuss recent progresses in the theoretical study of proton radioactivity and their impact on the present understanding of nuclear structure at the extremes of proton stability.

Dietary n-3 polyunsaturated fatty acid depletion activates caspases and decreases NMDA receptors in the brain of a transgenic mouse model of Alzheimer's disease.

Science.gov (United States)

Calon, Frédéric; Lim, Giselle P; Morihara, Takashi; Yang, Fusheng; Ubeda, Oliver; Salem, Norman; Frautschy, Sally A; Cole, Greg M

2005-08-01

Epidemiological data indicate that low n-3 polyunsaturated fatty acids (PFA) intake is a readily manipulated dietary risk factor for Alzheimer's disease (AD). Studies in animals confirm the deleterious effect of n-3 PFA depletion on cognition and on dendritic scaffold proteins. Here, we show that in transgenic mice overexpressing the human AD gene APPswe (Tg2576), safflower oil-induced n-3 PFA deficiency caused a decrease in N-methyl-D-aspartate (NMDA) receptor subunits, NR2A and NR2B, in the cortex and hippocampus with no loss of the presynaptic markers, synaptophysin and synaptosomal-associated protein 25 (SNAP-25). n-3 PFA depletion also decreased the NR1 subunit in the hippocampus and Ca2+/calmodulin-dependent protein kinase (CaMKII) in the cortex of Tg2576 mice. These effects of dietary n-3 PFA deficiency were greatly amplified in Tg2576 mice compared to nontransgenic mice. Loss of the NR2B receptor subunit was not explained by changes in mRNA expression, but correlated with p85alpha phosphatidylinositol 3-kinase levels. Most interestingly, n-3 PFA deficiency dramatically increased levels of protein fragments, corresponding to caspase/calpain-cleaved fodrin and gelsolin in Tg2576 mice. This effect was minimal in nontransgenic mice suggesting that n-3 PFA depletion potentiated caspase activation in the Tg2576 mouse model of AD. Dietary supplementation with docosahexaenoic acid (DHA; 22 : 6n-3) partly protected from NMDA receptor subunit loss and accumulation of fodrin and gelsolin fragments but fully prevented CaMKII decrease. The marked effect of dietary n-3 PFA on NMDA receptors and caspase/calpain activation in the cortex of an animal model of AD provide new insights into how dietary essential fatty acids may influence cognition and AD risk.

Molecular characterization of severin from Clonorchis sinensis excretory/secretory products and its potential anti-apoptotic role in hepatocarcinoma PLC cells.

Directory of Open Access Journals (Sweden)

Xueqing Chen

Full Text Available BACKGROUND: Clonorchiasis, caused by the infection of Clonorchis sinensis (C. sinensis, is a kind of neglected tropical disease, but it is highly related to cholangiocarcinoma and hepatocellular carcinoma (HCC. It has been well known that the excretory/secretory products of C. sinensis (CsESPs play key roles in clonorchiasis associated carcinoma. From genome and transcriptome of C. sinensis, we identified one component of CsESPs, severin (Csseverin, which had three putative gelsolin domains. Its homologues are supposed to play a vital role in apoptosis resistance of tumour cell. METHODOLOGY/PRINCIPAL FINDINGS: There was significant similarity in tertiary structures between human gelsolin and Csseverin by bioinformatics analysis. We identified that Csseverin expressed at life stage of adult worm, metacercaria and egg by the method of quantitative real-time PCR and western blotting. Csseverin distributed in vitellarium and intrauterine eggs of adult worm and tegument of metacercaria by immunofluorence assay. We obtained recombinant Csseverin (rCsseverin and confirmed that rCsseverin could bind with calciumion in circular dichroism spectrum analysis. It was demonstrated that rCsseverin was of the capability of actin binding by gel overlay assay and immunocytochemistry. Both Annexin V/PI assay and mitochondrial membrane potential assay of human hepatocarcinoma cell line PLC showed apoptosis resistance after incubation with different concentrations of rCsseverin. Morphological analysis, apoptosis-associated changes of mitochondrial membrane potential and Annexin V/PI apoptosis assay showed that co-incubation of PLC cells with rCsseverin in vitro led to an inhibition of apoptosis induced by serum-starved for 24 h. CONCLUSIONS/SIGNIFICANCE: Collectively, the molecular properties of Csseverin, a molecule of CsESPs, were characterized in our study. rCsseverin could cause obvious apoptotic inhibition in human HCC cell line. Csseverin might exacerbate the

Molecular Characterization of Severin from Clonorchis sinensis Excretory/Secretory Products and Its Potential Anti-apoptotic Role in Hepatocarcinoma PLC Cells

Science.gov (United States)

He, Lei; Wang, Xiaoyun; Liang, Pei; Chen, Wenjun; Bian, Meng; Ren, Mengyu; Lin, Jinsi; Liang, Chi; Xu, Jin; Wu, Zhongdao; Li, Xuerong; Huang, Yan; Yu, Xinbing

2013-01-01

Background Clonorchiasis, caused by the infection of Clonorchis sinensis (C. sinensis), is a kind of neglected tropical disease, but it is highly related to cholangiocarcinoma and hepatocellular carcinoma (HCC). It has been well known that the excretory/secretory products of C. sinensis (CsESPs) play key roles in clonorchiasis associated carcinoma. From genome and transcriptome of C. sinensis, we identified one component of CsESPs, severin (Csseverin), which had three putative gelsolin domains. Its homologues are supposed to play a vital role in apoptosis resistance of tumour cell. Methodology/Principal Findings There was significant similarity in tertiary structures between human gelsolin and Csseverin by bioinformatics analysis. We identified that Csseverin expressed at life stage of adult worm, metacercaria and egg by the method of quantitative real-time PCR and western blotting. Csseverin distributed in vitellarium and intrauterine eggs of adult worm and tegument of metacercaria by immunofluorence assay. We obtained recombinant Csseverin (rCsseverin) and confirmed that rCsseverin could bind with calciumion in circular dichroism spectrum analysis. It was demonstrated that rCsseverin was of the capability of actin binding by gel overlay assay and immunocytochemistry. Both Annexin V/PI assay and mitochondrial membrane potential assay of human hepatocarcinoma cell line PLC showed apoptosis resistance after incubation with different concentrations of rCsseverin. Morphological analysis, apoptosis-associated changes of mitochondrial membrane potential and Annexin V/PI apoptosis assay showed that co-incubation of PLC cells with rCsseverin in vitro led to an inhibition of apoptosis induced by serum-starved for 24 h. Conclusions/Significance Collectively, the molecular properties of Csseverin, a molecule of CsESPs, were characterized in our study. rCsseverin could cause obvious apoptotic inhibition in human HCC cell line. Csseverin might exacerbate the process of HCC

Progression of Late-Onset Stargardt Disease.

Science.gov (United States)

Lambertus, Stanley; Lindner, Moritz; Bax, Nathalie M; Mauschitz, Matthias M; Nadal, Jennifer; Schmid, Matthias; Schmitz-Valckenberg, Steffen; den Hollander, Anneke I; Weber, Bernhard H F; Holz, Frank G; van der Wilt, Gert Jan; Fleckenstein, Monika; Hoyng, Carel B

2016-10-01

Identification of sensitive biomarkers is essential to determine potential effects of emerging therapeutic trials for Stargardt disease. This study aimed to describe the natural history of late-onset Stargardt, and demonstrates the accuracy of retinal pigment epithelium (RPE) atrophy progression as an outcome measure. We performed a retrospective cohort study collecting multicenter data from 47 patients (91 eyes) with late-onset Stargardt, defined by clinical phenotype, at least one ABCA4 mutation, and age at disease onset ≥ 45 years. We analyzed RPE atrophy progression on fundus autofluorescence and near-infrared reflectance imaging using semiautomated software and a linear mixed model. We performed sample size calculations to assess the power in a simulated 2-year interventional study and assessed visual endpoints using time-to-event analysis. Over time, progression of RPE atrophy was observed (mean: 0.22 mm/year, 95% confidence interval [CI]: 0.19-0.27). By including only patients with bilateral RPE atrophy in a future trial, 32 patients are needed to reach a power of 83.9% (95% CI: 83.1-84.6), assuming a fixed therapeutic effect size of 30%. We found a median interval between disease onset and visual acuity decline to 20/32, 20/80, and 20/200 of 2.74 (95% CI: 0.54-4.41), 10.15 (95% CI: 6.13-11.38), and 11.38 (95% CI: 6.13-13.34) years, respectively. We show that RPE atrophy represents a robust biomarker to monitor disease progression in future therapeutic trials. In contrast, the variability in terms of the course of visual acuity was high.

Ultrasonic Monitoring of the Progress of Lactic Acid Fermentation

Science.gov (United States)

Masuzawa, Nobuyoshi; Kimura, Akihiro; Ohdaira, Etsuzo

2003-05-01

Promotion of lactic acid fermentation by ultrasonic irradiation has been attempted. It is possible to determine the progress of fermentation and production of a curd, i.e., yoghurt and or kefir, by measuring acidity using a pH meter. However, this method is inconvenient and indirect for the evaluation of the progress of lactic acid fermentation under anaerobic condition. In this study, an ultrasonic monitoring method for evaluating the progress of lactic acid fermentation was examined.

Progress in inertial fusion

International Nuclear Information System (INIS)

Hogan, W.; Storm, E.

1985-10-01

The requirements for high gain in inertial confinement are given in terms of target implosion requirements. Results of experimental studies of the laser/target interaction and of the dynamics of laser implosion. A report of the progress of advanced laser development is also presented. 3 refs., 8 figs., 1 tab

Recent progress in Biophysics

International Nuclear Information System (INIS)

Bemski, G.

1980-03-01

Recent progress in biophysics is reviewed, and three examples of the use of physical techniques and ideas in biological research are given. The first one deals with the oxygen transporting protein-hemoglobin, the second one with photosynthesis, and the third one with image formation, using nuclear magnetic resonance. (Author) [pt

Continuing progress on a lattice QCD software infrastructure

International Nuclear Information System (INIS)

Joo, B

2008-01-01

We report on the progress of the software effort in the QCD application area of SciDAC. In particular, we discuss how the software developed under SciDAC enabled the aggressive exploitation of leadership computers, and we report on progress in the area of QCD software for multi-core architectures

Progressive Coding and Presentation of Maps for Internet Applications

DEFF Research Database (Denmark)

Jensen, Ole Riis; Forchhammer, Søren Otto

1999-01-01

A new lossless context based method for content progressive coding of images as maps is proposed.......A new lossless context based method for content progressive coding of images as maps is proposed....

Interventions to slow progression of myopia in children.

Science.gov (United States)

Walline, Jeffrey J; Lindsley, Kristina; Vedula, Satyanarayana S; Cotter, Susan A; Mutti, Donald O; Twelker, J Daniel

2011-12-07

Nearsightedness (myopia) causes blurry vision when looking at distant objects. Highly nearsighted people are at greater risk of several vision-threatening problems such as retinal detachments, choroidal atrophy, cataracts and glaucoma. Interventions that have been explored to slow the progression of myopia include bifocal spectacles, cycloplegic drops, intraocular pressure-lowering drugs, muscarinic receptor antagonists and contact lenses. The purpose of this review was to systematically assess the effectiveness of strategies to control progression of myopia in children. To assess the effects of several types of interventions, including eye drops, undercorrection of nearsightedness, multifocal spectacles and contact lenses, on the progression of nearsightedness in myopic children younger than 18 years. We compared the interventions of interest with each other, to single vision lenses (SVLs) (spectacles), placebo or no treatment. We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2011, Issue 10), MEDLINE (January 1950 to October 2011), EMBASE (January 1980 to October 2011), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to October 2011), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com) and ClinicalTrials.gov (http://clinicaltrials.gov). There were no date or language restrictions in the electronic searches for trials. The electronic databases were last searched on 11 October 2011. We also searched the reference lists and Science Citation Index for additional, potentially relevant studies. We included randomized controlled trials (RCTs) in which participants were treated with spectacles, contact lenses or pharmaceutical agents for the purpose of controlling progression of myopia. We excluded trials where participants were older than 18 years at baseline or participants had less than -0.25 diopters (D) spherical equivalent myopia. Two review authors

Lipid-Altering Therapies and the Progression of Atherosclerotic Disease

International Nuclear Information System (INIS)

Wierzbicki, Anthony S.

2007-01-01

Lipids play a key role in the progression of atherosclerosis, and lipid-lowering therapies have been studied for 30 years in coronary disease. Measurement of the progression of atherosclerosis through carotid intima-media thickness, coronary mean lumen diameter, and, mostly recently, intravascular ultrasound is generally accepted. This article reviews the role of lipid-lowering therapies in changing the rate of atherosclerosis progression in the coronary and carotid circulations. Statins are the primary therapy used to reduce atherosclerosis and cardiovascular events, including strokes and transient ischemic attacks, and have benefits in reducing events in patients undergoing carotid endarterectomy. In contrast, data for other agents, including fibrates and nicotinic acid, in reducing the progression of atherosclerosis are less extensive and not as well known. There is increasing interest in optimizing the whole lipid profile, as this might deliver extra benefits over and above statin therapy alone. Initial proof of this concept has recently come from studies that measured the progression of atherosclerosis and showed that adding nicotinic acid to statin therapy and, more directly, infusion of high-density lipoprotein-like particles reduced progression and indeed might induce regression of the disease. It is likely that the management of significant carotid stenosis will become ever more drug focused and will be customized to the lipid profile of each patient with intervention reserved only for late-stage symptomatic disease

Risk of progression in macula-on rhegmatogenous retinal detachment.

Science.gov (United States)

Callizo, Josep; Pfeiffer, Sebastian; Lahme, Eva; van Oterendorp, Christian; Khattab, Mohammed; Bemme, Sebastian; Kulanga, Miroslav; Hoerauf, Hans; Feltgen, Nicolas

2017-08-01

To identify factors that may lead to a rapid progression in macula-on rhegmatogenous retinal detachment (RRD), in particular, those that may lead to macular involvement. Observational, prospective, single-center study. Patients referred for surgery due to primary rhegmatogenous retinal detachment with the macula on between 2009 and 2013 were included. Relevant factors analyzed included age, time delay until surgery, lens status, myopia, the detachment's location and configuration as well as number, size and type of retinal breaks. Eyes underwent optical coherence tomography to detect macular detachment. A multivariate analysis was performed to investigate the effect of several factors in the progression of retinal detachment. A total of 116 eyes of 116 patients were included. Mean time delay between admission and surgery was 1.8 ± 1.4 days. Progression was observed in 19.8% of the eyes. Of those, 47.8% presented macular detachment. Ten of the 11 (90.9%) eyes presenting progression involving the macula also exhibited a bullous configuration, which was the only parameter that correlated significantly with detachment progression in patients with (p = 0.0036) and without (p = 0.0014) macular involvement. For the first time in a prospective trial, a bullous configuration was found to be a highly significant predictor for progression in macula-on detachments. Our data support prompt surgery in patients diagnosed with bullous macula-on RRD.

Solar lease grant program. Technical progress report

Energy Technology Data Exchange (ETDEWEB)

1981-04-01

Progress on a lease program for the installation of a solar water heater with no installation charge is reported. Information on the announcement of the program, the selection of participants, the contractural agreement, progress on installation of equipment, monitoring, and evaluation is summarized. The status of the budget concerned with the program is announced. Forms used for applications for the program and an announcement from Resource Alternatives for Cilco customers are presented.

Progressive-Era Resources on the World Wide Web.

Science.gov (United States)

Howenstein, Amanda

1999-01-01

Provides a list of Progressive-era websites with the address and a detailed description of each of the websites. Includes topics such as the womens suffrage movement, the Triangle Shirtwaist Factory fire, the Prohibition, labor-management conflicts, the Hull House, the Chicago fire, Emma Goldman, Progressive-era entertainment, and the Worlds Fair.…

Progress in Heavy Ion Fusion

International Nuclear Information System (INIS)

Herrmannsfeldt, W.B.

1988-09-01

The progress of the field of Heavy Ion Fusion has been documented in the proceedings of the series of International Symposia that, in recent years, have occurred every second year. The latest of these conferences was hosted by Gesellshaft fuer Schwerionenforshung (GSI) in Darmstadt, West Germany, June 28-30, 1988. For this report, a few highlights from the conference are selected, stressing experimental progress and prospects for future advances. A little extra time is devoted to report on the developments at the Lawrence Berkeley Laboratory (LBL) which is the center for most of the HIFAR program. The Director of the HIFAR program at LBL is Denis Keefe, who presented the HIF report at the last two of the meetings in this series, and in whose place the author is appearing now. 4 refs., 1 fig

Progress Check Module; Basic Electricity and Electronics Individualized Learning System. Progress Check Booklet.

Science.gov (United States)

Bureau of Naval Personnel, Washington, DC.

The Progress Check Booklet is designed to be used by the student working in the programed course to determine if he has mastered the concepts in the course booklets on: electrical current; voltage; resistance; measuring current and voltage in series circuits; relationships of current, voltage, and resistance; parellel circuits; combination…

Peak Oil and the Everyday Complexity of Human Progress Narratives

Directory of Open Access Journals (Sweden)

John C. Pruit

2012-11-01

Full Text Available The “big” story of human progress has polarizing tendencies featuring the binary options of progress or decline. I consider human progress narratives in the context of everyday life. Analysis of the “little” stories from two narrative environments focusing on peak oil offers a more complex picture of the meaning and contours of the narrative. I consider the impact of differential blog site commitments to peak oil perspectives and identify five narrative types culled from two narrative dimensions. I argue that the lived experience complicates human progress narratives, which is no longer an either/or proposition.

Monthly oral methylprednisolone pulse treatment in progressive multiple sclerosis

DEFF Research Database (Denmark)

Ratzer, Rikke; Iversen, Pernille; Börnsen, Lars

2016-01-01

BACKGROUND: There is a large unmet need for treatments for patients with progressive multiple sclerosis (MS). Phase 2 studies with cerebrospinal fluid (CSF) biomarker outcomes may be well suited for the initial evaluation of efficacious treatments. OBJECTIVE: To evaluate the effect of monthly oral...... methylprednisolone pulse treatment on intrathecal inflammation in progressive MS. METHODS: In this open-label phase 2A study, 15 primary progressive and 15 secondary progressive MS patients received oral methylprednisolone pulse treatment for 60 weeks. Primary outcome was changes in CSF concentrations of osteopontin...... no change in the CSF concentration of osteopontin, but we observed significant improvement in clinical scores, MTR, DTI and some secondary CSF outcome measures. Adverse events were well-known side effects to methylprednisolone. CONCLUSION: Monthly methylprednisolone pulse treatment was safe, but had...

Defective lysosomal proteolysis and axonal transport are early pathogenic events that worsen with age leading to increased APP metabolism and synaptic Abeta in transgenic APP/PS1 hippocampus.

Science.gov (United States)

Torres, Manuel; Jimenez, Sebastian; Sanchez-Varo, Raquel; Navarro, Victoria; Trujillo-Estrada, Laura; Sanchez-Mejias, Elisabeth; Carmona, Irene; Davila, Jose Carlos; Vizuete, Marisa; Gutierrez, Antonia; Vitorica, Javier

2012-11-22

Axonal pathology might constitute one of the earliest manifestations of Alzheimer disease. Axonal dystrophies were observed in Alzheimer's patients and transgenic models at early ages. These axonal dystrophies could reflect the disruption of axonal transport and the accumulation of multiple vesicles at local points. It has been also proposed that dystrophies might interfere with normal intracellular proteolysis. In this work, we have investigated the progression of the hippocampal pathology and the possible implication in Abeta production in young (6 months) and aged (18 months) PS1(M146L)/APP(751sl) transgenic mice. Our data demonstrated the existence of a progressive, age-dependent, formation of axonal dystrophies, mainly located in contact with congophilic Abeta deposition, which exhibited tau and neurofilament hyperphosphorylation. This progressive pathology was paralleled with decreased expression of the motor proteins kinesin and dynein. Furthermore, we also observed an early decrease in the activity of cathepsins B and D, progressing to a deep inhibition of these lysosomal proteases at late ages. This lysosomal impairment could be responsible for the accumulation of LC3-II and ubiquitinated proteins within axonal dystrophies. We have also investigated the repercussion of these deficiencies on the APP metabolism. Our data demonstrated the existence of an increase in the amyloidogenic pathway, which was reflected by the accumulation of hAPPfl, C99 fragment, intracellular Abeta in parallel with an increase in BACE and gamma-secretase activities. In vitro experiments, using APPswe transfected N2a cells, demonstrated that any imbalance on the proteolytic systems reproduced the in vivo alterations in APP metabolism. Finally, our data also demonstrated that Abeta peptides were preferentially accumulated in isolated synaptosomes. A progressive age-dependent cytoskeletal pathology along with a reduction of lysosomal and, in minor extent, proteasomal activity could be

Progress in optics

CERN Document Server

Wolf, Emil

2008-01-01

In the fourty-six years that have gone by since the first volume of Progress in Optics was published, optics has become one of the most dynamic fields of science. The volumes in this series which have appeared up to now contain more than 300 review articles by distinguished research workers, which have become permanent records for many important developments.- Metamaterials- Polarization Techniques- Linear Baisotropic Mediums- Ultrafast Optical Pulses- Quantum Imaging- Point-Spread Funcions- Discrete Wigner Functions

Theoretical nuclear structure. Progress report for 1997

International Nuclear Information System (INIS)

Nazarewicz, W.; Strayer, M.R.

1997-01-01

This research effort is directed toward theoretical support and guidance for the fields of radioactive ion beam physics, gamma-ray spectroscopy, and the interface between nuclear structure and nuclear astrophysics. The authors report substantial progress in all these areas. One measure of progress is publications and invited material. The research described here has led to more than 25 papers that are published, accepted, or submitted to refereed journals, and to 25 invited presentations at conferences and workshops

Preventing Breast Cancer: Making Progress

Science.gov (United States)

... Navigation Bar Home Current Issue Past Issues Preventing Breast Cancer: Making Progress Past Issues / Fall 2006 Table of ... 000 women will have been diagnosed with invasive breast cancer, and nearly 41,000 women will die from ...

Fibrodysplasia ossificans progressive: a case report and radiographic findings

International Nuclear Information System (INIS)

Araujo Junior, Cyrillo Rodrigues de; Carvalho, Tarcisio Nunes; Costa, Marlos Augusto Bittencourt; Lobo, Leonardo Valadares; Fonseca, Cristiano Rezio; Teixiera, Kim-Ir-Sem Santos

2001-01-01

Fibrodysplasia ossificans progressive is a rare hereditary connective tissue disease characterized by disseminated soft tissue ossification and congenital abnormality of the extremities. It is genetically inherited as a dominant trait with complete penetrance but variable expression. The onset takes place during childhood and the progressive involvement of the spine and proximal extremities leads to immobilization and articular deformity. We report a case of a 22-year-old male patient with typical symptoms of fibrodysplasia ossificans progressive and discuss the new advances in the diagnosis and pathophysiology. (author)

Smoldering multiple myeloma risk factors for progression

DEFF Research Database (Denmark)

Sørrig, Rasmus; Klausen, Tobias W; Salomo, Morten

2016-01-01

Several risk scores for disease progression in Smoldering Multiple Myeloma (SMM) patients have been proposed, however, all have been developed using single center registries. To examine risk factors for time to progression (TTP) to Multiple Myeloma (MM) for SMM we analyzed a nationwide population......-based cohort of 321 newly diagnosed SMM patients registered within the Danish Multiple Myeloma Registry between 2005 and 2014. Significant univariable risk factors for TTP were selected for multivariable Cox regression analyses. We found that both an M-protein ≥ 30g/l and immunoparesis significantly influenced......-high risk of transformation to MM. Using only immunoparesis and M-protein ≥ 30g/l, we created a scoring system to identify low, intermediate and high risk SMM. This first population-based study of SMM patients confirms that an M-protein ≥ 30g/l and immunoparesis remain important risk factors for progression...

Scientific instruments, scientific progress and the cyclotron

International Nuclear Information System (INIS)

Baird, David; Faust, Thomas

1990-01-01

Philosophers speak of science in terms of theory and experiment, yet when they speak of the progress of scientific knowledge they speak in terms of theory alone. In this article it is claimed that scientific knowledge consists of, among other things, scientific instruments and instrumental techniques and not simply of some kind of justified beliefs. It is argued that one aspect of scientific progress can be characterized relatively straightforwardly - the accumulation of new scientific instruments. The development of the cyclotron is taken to illustrate this point. Eight different activities which promoted the successful completion of the cyclotron are recognised. The importance is in the machine rather than the experiments which could be run on it and the focus is on how the cyclotron came into being, not how it was subsequently used. The completed instrument is seen as a useful unit of scientific progress in its own right. (UK)

Targeting the extracellular matrix to disrupt cancer progression

Directory of Open Access Journals (Sweden)

Freja Albjerg Venning

2015-10-01

Full Text Available Metastatic complications are responsible for more than 90% of cancer related deaths. The progression from an isolated tumor to disseminated metastatic disease is a multi-step process, with each step involving intricate cross-talk between the cancer cells and their non-cellular surroundings, the extracellular matrix (ECM. Many ECM proteins are significantly de-regulated during the progression of cancer, causing both biochemical and biomechanical changes that together promote the metastatic cascade. In this review, the influence of several ECM proteins on these multiple steps of cancer spread is summarized. In addition, we highlight the promising (pre-clinical data showing benefits of targeting these ECM macromolecules to prevent cancer progression.

Model-based setup assistant for progressive tools

Science.gov (United States)

Springer, Robert; Gräler, Manuel; Homberg, Werner; Henke, Christian; Trächtler, Ansgar

2018-05-01

In the field of production systems, globalization and technological progress lead to increasing requirements regarding part quality, delivery time and costs. Hence, today's production is challenged much more than a few years ago: it has to be very flexible and produce economically small batch sizes to satisfy consumer's demands and avoid unnecessary stock. Furthermore, a trend towards increasing functional integration continues to lead to an ongoing miniaturization of sheet metal components. In the industry of electric connectivity for example, the miniaturized connectors are manufactured by progressive tools, which are usually used for very large batches. These tools are installed in mechanical presses and then set up by a technician, who has to manually adjust a wide range of punch-bending operations. Disturbances like material thickness, temperatures, lubrication or tool wear complicate the setup procedure. In prospect of the increasing demand of production flexibility, this time-consuming process has to be handled more and more often. In this paper, a new approach for a model-based setup assistant is proposed as a solution, which is exemplarily applied in combination with a progressive tool. First, progressive tools, more specifically, their setup process is described and based on that, the challenges are pointed out. As a result, a systematic process to set up the machines is introduced. Following, the process is investigated with an FE-Analysis regarding the effects of the disturbances. In the next step, design of experiments is used to systematically develop a regression model of the system's behaviour. This model is integrated within an optimization in order to calculate optimal machine parameters and the following necessary adjustment of the progressive tool due to the disturbances. Finally, the assistant is tested in a production environment and the results are discussed.

Unequal Error Protected JPEG 2000 Broadcast Scheme with Progressive Fountain Codes

OpenAIRE

Chen, Zhao; Xu, Mai; Yin, Luiguo; Lu, Jianhua

2012-01-01

This paper proposes a novel scheme, based on progressive fountain codes, for broadcasting JPEG 2000 multimedia. In such a broadcast scheme, progressive resolution levels of images/video have been unequally protected when transmitted using the proposed progressive fountain codes. With progressive fountain codes applied in the broadcast scheme, the resolutions of images (JPEG 2000) or videos (MJPEG 2000) received by different users can be automatically adaptive to their channel qualities, i.e. ...

Renewable energy progress and biofuels sustainability

Energy Technology Data Exchange (ETDEWEB)

Hamelinck, C.; De Lovinfosse, I.; Koper, M.; Beestermoeller, C.; Nabe, C.; Kimmel, M.; Van den Bos, A.; Yildiz, I.; Harteveld, M. [Ecofys Netherlands, Utrecht (Netherlands); Ragwitz, M.; Steinhilber, S. [Fraunhofer Institut fuer System- und Innovationsforschung ISI, Karlsruhe (Germany); Nysten, J.; Fouquet, D. [Becker Buettner Held BBH, Munich (Germany); Resch, G.; Liebmann, L.; Ortner, A.; Panzer, C. [Energy Economics Group EEG, Vienna University of Technology, Vienna (Austria); Walden, D.; Diaz Chavez, R.; Byers, B.; Petrova, S.; Kunen, E. [Winrock International, Brussels (Belgium); Fischer, G.

2013-03-15

On 27 March 2013, the European Commission published its first Renewable Energy Progress Report under the framework of the 2009 Renewable Energy Directive. Since the adoption of this directive and the introduction of legally binding renewable energy targets, most Member States experienced significant growth in renewable energy consumption. 2010 figures indicate that the EU as a whole is on its trajectory towards the 2020 targets with a renewable energy share of 12.7%. Moreover, in 2010 the majority of Member States already reached their 2011/2012 interim targets set in the Directive. However, as the trajectory grows steeper towards the end, more efforts will still be needed from the Member States in order to reach the 2020 targets. With regard to the EU biofuels and bioliquids sustainability criteria, Member States' implementation of the biofuels scheme is considered too slow. In accordance with the reporting requirements set out in the 2009 Directive on Renewable Energy, every two years the European Commission publishes a Renewable Energy Progress Report. The report assesses Member States' progress in the promotion and use of renewable energy along the trajectory towards the 2020 renewable energy targets. The report also describes the overall renewable energy policy developments in each Member State and their compliance with the measures outlined in the Directive and the National Renewable Energy Action Plans. Moreover, in accordance with the Directive, it reports on the sustainability of biofuels and bioliquids consumed in the EU and the impacts of this consumption. A consortium led by Ecofys was contracted by the European Commission to perform support activities concerning the assessment of progress in renewable energy and sustainability of biofuels.

Renewable energy progress and biofuels sustainability

Energy Technology Data Exchange (ETDEWEB)

Hamelinck, C.; De Lovinfosse, I.; Koper, M.; Beestermoeller, C.; Nabe, C.; Kimmel, M.; Van den Bos, A.; Yildiz, I.; Harteveld, M. [Ecofys Netherlands, Utrecht (Netherlands); Ragwitz, M.; Steinhilber, S. [Fraunhofer Institut fuer System- und Innovationsforschung ISI, Karlsruhe (Germany); Nysten, J.; Fouquet, D. [Becker Buettner Held BBH, Munich (Germany); Resch, G.; Liebmann, L.; Ortner, A.; Panzer, C. [Energy Economics Group EEG, Vienna University of Technology, Vienna (Austria); Walden, D.; Diaz Chavez, R.; Byers, B.; Petrova, S.; Kunen, E. [Winrock International, Brussels (Belgium); Fischer, G.

2013-03-15

On 27 March 2013, the European Commission published its first Renewable Energy Progress Report under the framework of the 2009 Renewable Energy Directive. Since the adoption of this directive and the introduction of legally binding renewable energy targets, most Member States experienced significant growth in renewable energy consumption. 2010 figures indicate that the EU as a whole is on its trajectory towards the 2020 targets with a renewable energy share of 12.7%. Moreover, in 2010 the majority of Member States already reached their 2011/2012 interim targets set in the Directive. However, as the trajectory grows steeper towards the end, more efforts will still be needed from the Member States in order to reach the 2020 targets. With regard to the EU biofuels and bioliquids sustainability criteria, Member States' implementation of the biofuels scheme is considered too slow. In accordance with the reporting requirements set out in the 2009 Directive on Renewable Energy, every two years the European Commission publishes a Renewable Energy Progress Report. The report assesses Member States' progress in the promotion and use of renewable energy along the trajectory towards the 2020 renewable energy targets. The report also describes the overall renewable energy policy developments in each Member State and their compliance with the measures outlined in the Directive and the National Renewable Energy Action Plans. Moreover, in accordance with the Directive, it reports on the sustainability of biofuels and bioliquids consumed in the EU and the impacts of this consumption. A consortium led by Ecofys was contracted by the European Commission to perform support activities concerning the assessment of progress in renewable energy and sustainability of biofuels.

Tracking SDG7 : The Energy Progress Report 2018

OpenAIRE

International Energy Agency; International Renewable Energy Agency; United Nations; World Bank Group; World Health Organization

2018-01-01

The Energy Progress Report provides a global dashboard on progress towards Sustainable Development Goal 7 (SDG7). The report is a joint effort of the International Energy Agency (IEA), the International Renewable Energy Agency (IRENA), United Nations Statistics Division (UNSD), the World Bank, and the World Health Organization (WHO), which the United Nations (UN) has named as global custod...

Study of progressive depigmentation of dog′s muzzle

OpenAIRE

Shah K

1991-01-01

A new animal model is developed using dog′s muzzle to demonstrate progressive depigmen-tation after birth. Dog′s muzzle is heavily pigmented with pigment melanin and looks black in colour. Progressive depigmentation was observed two months after birth in a pup born with a depigmented mucous membrane of the mouth and lips. This resembles the vitiligo of humans.

Progression of Myopic Maculopathy during 18-Year Follow-up.

Science.gov (United States)

Fang, Yuxin; Yokoi, Tae; Nagaoka, Natsuko; Shinohara, Kosei; Onishi, Yuka; Ishida, Tomoka; Yoshida, Takeshi; Xu, Xian; Jonas, Jost B; Ohno-Matsui, Kyoko

2018-06-01

To examine the progression pattern of myopic maculopathy. Retrospective, observational case series. Highly myopic patients who had been followed up for 10 years or more. Using fundus photographs, myopic features were differentiated according to Meta-analysis of Pathologic Myopia (META-PM) Study Group recommendations. Progression pattern of maculopathy. The study included 810 eyes of 432 patients (mean age, 42.3±16.8 years; mean axial length, 28.8±1.9 mm; mean follow-up, 18.7±7.1 years). The progression rate of myopic maculopathy was 47.0 per 1000 eye-years. Within the pathologic myopia (PM) group (n = 521 eyes), progression of myopic maculopathy was associated with female gender (odds ratio [OR], 2.21; P = 0.001), older age (OR, 1.03; P = 0.002), longer axial length (OR, 1.20; P = 0.007), greater axial elongation (OR, 1.45; P = 0.005), and development of parapapillary atrophy (PPA; OR, 3.14; P < 0.001). Diffuse atrophy, found in 217 eyes without choroidal neovascularization (CNV) or lacquer cracks (LCs) at baseline, progressed in 111 (51%) eyes, leading to macular diffuse atrophy (n = 64; 64/111 or 58%), patchy atrophy (n = 59; 53%), myopic CNV (n = 18; 16%), LCs (n = 9; 5%), and patchy-related macular atrophy (n = 3; 3%). Patchy atrophy, detected in 63 eyes without CNV or LCs at baseline, showed progression in 60 eyes (95%), leading to enlargement of original patchy atrophy (n = 59; 59/60 or 98%), new patchy atrophy (n = 29; 48%), CNV-related macular atrophy (n = 13; 22%), and patchy-related macular atrophy (n = 5; 8%). Of 66 eyes with LCs, 43 eyes (65%) showed progression with development of new patchy atrophy (n = 38; 38/43 or 88%) and new LCs (n = 7; 16%). Reduction in best-corrected visual acuity (BCVA) was associated mainly (all P < 0.001) with the development of CNV or CNV-related macular atrophy and enlargement of macular atrophy. The most frequent progression patterns were an extension of peripapillary diffuse atrophy to macular diffuse

The Modern Idea of Progress by Jean A. Condorcet

Directory of Open Access Journals (Sweden)

Podgórski Ryszard

2017-12-01

Full Text Available The 18th century is the opening to cognitive progress (epistemology which becomes the core of historical progress. They were defined more precisely by Robert Turgot (1727-1781. Turgot’s lecture entitled Discours sur l´histoire universalle of 1750 significantly contributed to the notion of “progress”. The lecture presented a broad programme of historical studies whose object was humanity striving for perfection. Turgot’s programme was implemented by his friend Jean Antoine de Condorcet (1743-1794. He contained the interpretation of his programme of historical progress in Esquisse d´un tableau historique des progrés de l´esprit humain (A sketch of the picture of progress of human spirit through the ages. It was 1794 and in that year Condorcet was imprisoned. Jean Antoine de Condorcet proposed a secular mechanism of progress which was to take place through development of knowledge and science. In his outline of the development of humanity, Condorcet emphasised that the progress of humanity occurs because of efforts of people without interference of divine factors. Man is able to improve due to his own mind. The history of humanity is presented in his philosophy as a linear, continuous process taking place along a rising line, whereas the description of progress includes both past times and the future. In this way, Condorcet showed the perspective of further development of humanity in the direction of a system consistent with the law of nature and the complete elimination of suffering. This view of Condorcet motivated August Comte (1798-1857 when he built the “first philosophy”, and Claude Adrien Helvétius (1715-1771 and Paul Henry d´Holbach (1723-1789.

[Specificities of the logopenic variant of primary progressive aphasia].

Science.gov (United States)

Magnin, E; Teichmann, M; Martinaud, O; Moreaud, O; Ryff, I; Belliard, S; Pariente, J; Moulin, T; Vandel, P; Démonet, J-F

2015-01-01

The logopenic variant of primary progressive aphasia is a syndrome with neuropsychological and linguistic specificities, including phonological loop impairment for which diagnosis is currently mainly based on the exclusion of the two other variants, semantic and nonfluent/agrammatic primary progressive aphasia. The syndrome may be underdiagnosed due (1) to mild language difficulties during the early stages of the disease or (2) to being mistaken for mild cognitive impairment or Alzheimer's disease when the evaluation of episodic memory is based on verbal material and (3) finally, it is not uncommon that the disorders are attributed to psychiatric co-morbidities such as, for example, anxiety. Moreover, compared to other variants of primary progressive aphasia, brain abnormalities are different. The left temporoparietal junction is initially affected. Neuropathology and biomarkers (cerebrospinal fluid, molecular amyloid nuclear imaging) frequently reveal Alzheimer's disease. Consequently this variant of primary progressive aphasia does not fall under the traditional concept of frontotemporal lobar degeneration. These distinctive features highlight the utility of correct diagnosis, classification, and use of biomarkers to show the neuropathological processes underlying logopenic primary progressive aphasia. The logopenic variant of primary progressive aphasia is a specific form of Alzheimer's disease frequently presenting a rapid decline; specific linguistic therapies are needed. Further investigation of this syndrome is needed to refine screening, improve diagnostic criteria and better understand the epidemiology and the biological mechanisms involved. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Caffeine, creatine, GRIN2A and Parkinson's disease progression.

Science.gov (United States)

Simon, David K; Wu, Cai; Tilley, Barbara C; Lohmann, Katja; Klein, Christine; Payami, Haydeh; Wills, Anne-Marie; Aminoff, Michael J; Bainbridge, Jacquelyn; Dewey, Richard; Hauser, Robert A; Schaake, Susen; Schneider, Jay S; Sharma, Saloni; Singer, Carlos; Tanner, Caroline M; Truong, Daniel; Wei, Peng; Wong, Pei Shieen; Yang, Tianzhong

2017-04-15

Caffeine is neuroprotective in animal models of Parkinson's disease (PD) and caffeine intake is inversely associated with the risk of PD. This association may be influenced by the genotype of GRIN2A, which encodes an NMDA-glutamate-receptor subunit. In two placebo-controlled studies, we detected no association of caffeine intake with the rate of clinical progression of PD, except among subjects taking creatine, for whom higher caffeine intake was associated with more rapid progression. We now have analyzed data from 420 subjects for whom DNA samples and caffeine intake data were available from a placebo-controlled study of creatine in PD. The GRIN2A genotype was not associated with the rate of clinical progression of PD in the placebo group. However, there was a 4-way interaction between GRIN2A genotype, caffeine, creatine and the time since baseline. Among subjects in the creatine group with high levels of caffeine intake, but not among those with low caffeine intake, the GRIN2A T allele was associated with more rapid progression (p=0.03). These data indicate that the deleterious interaction between caffeine and creatine with respect to rate of progression of PD is influenced by GRIN2A genotype. This example of a genetic factor interacting with environmental factors illustrates the complexity of gene-environment interactions in the progression of PD. Copyright © 2017 Elsevier B.V. All rights reserved.

Monthly oral methylprednisolone pulse treatment in progressive multiple sclerosis.

Science.gov (United States)

Ratzer, Rikke; Iversen, Pernille; Börnsen, Lars; Dyrby, Tim B; Romme Christensen, Jeppe; Ammitzbøll, Cecilie; Madsen, Camilla Gøbel; Garde, Ellen; Lyksborg, Mark; Andersen, Birgit; Hyldstrup, Lars; Sørensen, Per Soelberg; Siebner, Hartwig R; Sellebjerg, Finn

2016-06-01

There is a large unmet need for treatments for patients with progressive multiple sclerosis (MS). Phase 2 studies with cerebrospinal fluid (CSF) biomarker outcomes may be well suited for the initial evaluation of efficacious treatments. To evaluate the effect of monthly oral methylprednisolone pulse treatment on intrathecal inflammation in progressive MS. In this open-label phase 2A study, 15 primary progressive and 15 secondary progressive MS patients received oral methylprednisolone pulse treatment for 60 weeks. Primary outcome was changes in CSF concentrations of osteopontin. Secondary outcomes were other CSF biomarkers of inflammation, axonal damage and demyelination; clinical scores; magnetic resonance imaging measures of disease activity, magnetization transfer ratio (MTR) and diffusion tensor imaging (DTI); motor evoked potentials; and bone density scans. We found no change in the CSF concentration of osteopontin, but we observed significant improvement in clinical scores, MTR, DTI and some secondary CSF outcome measures. Adverse events were well-known side effects to methylprednisolone. Monthly methylprednisolone pulse treatment was safe, but had no effect on the primary outcome. However, improvements in secondary clinical and MRI outcome measures suggest that this treatment regimen may have a beneficial effect in progressive MS. © The Author(s), 2015.

Tracking Progress in Carbon Capture and Storage

Energy Technology Data Exchange (ETDEWEB)

NONE

2012-09-06

At the second Clean Energy Ministerial in Abu Dhabi, April 2011 (CEM 2), the Carbon Capture, Use and Storage Action Group (CCUS AG) presented seven substantive recommendations to Energy Ministers on concrete, near-term actions to accelerate global carbon capture and storage (CCS) deployment. Twelve CCUS AG governments agreed to advance progress against the 2011 recommendations by the third Clean Energy Ministerial (London, 25-26 April 2012) (CEM 3). Following CEM 2, the CCUS AG requested the IEA and the Global CCS Institute to report on progress made against the 2011 recommendations at CEM 3. Tracking Progress in Carbon Capture and Storage: International Energy Agency/Global CCS Institute report to the third Clean Energy Ministerial responds to that request. The report considers a number of key questions. Taken as a whole, what advancements have committed CCUS AG governments made against the 2011 recommendations since CEM 2? How can Energy Ministers continue to drive progress to enable CCS to fully contribute to climate change mitigation? While urgent further action is required in all areas, are there particular areas that are currently receiving less policy attention than others, where efforts could be redoubled? The report concludes that, despite developments in some areas, significant further work is required. CCS financing and industrial applications continue to represent a particularly serious challenge.

Recent progress in medical imaging technology

International Nuclear Information System (INIS)

Endo, Masahiro

2004-01-01

Medical imaging is name of methods for diagnosis and therapy, which make visible with physical media such as X-ray, structures and functions of man's inside those are usually invisible. These methods are classified by the physical media into ultrasound imaging, magnetic resonance imaging, nuclear medicine imaging and X-ray imaging etc. Having characteristics different from one another, these are used complementarily in medical fields though in some case being competitive. Medical imaging is supported by highly progressed technology, which is called medical imaging technology. This paper describes a survey of recent progress of medical imaging technology in magnetic resonance imaging, nuclear medicine imaging and X-ray imaging. (author)

Treatment progress of diabetic macular edema

Directory of Open Access Journals (Sweden)

Dou Kou

2016-05-01

Full Text Available Diabetic retinopathy(DR,which can cause blindness, is a serious eye diseases. Diabetic macular edema(DME, often causes irreversible vision loss, can occur in any period of DR. The treatment of DME, including laser photocoagulation, anti-inflammatory therapy, anti-VEGF therapy and surgical treatment have made great progress in recent years as the researches on the pathogenesis deepening. The innovation of minimally invasive technique also proved the surgical treatment more convenience. The joint application of a variety of treatments, also become the main trend of treatment. A review of the present status and progress of the treatment was made in this paper.

The art of progressive censoring applications to reliability and quality

CERN Document Server

Balakrishnan, N

2014-01-01

This monograph offers a thorough and updated guide to the theory and methods of progressive censoring, an area that has experienced tremendous growth in recent years. Progressive censoring, originally proposed in the 1950s, is an efficient method of handling samples from industrial experiments involving lifetimes of units that have either failed or censored in a progressive fashion during the life test, with many practical applications to reliability and quality. Key topics and features: Data sets from the literature as well as newly simulated data sets are used to illustrate concepts throughout the text Emphasis on real-life applications to life testing, reliability, and quality control Discussion of parametric and nonparametric inference Coverage of experimental design with optimal progressive censoring The Art of Progressive Censoring is a valuable reference for graduate students, researchers, and practitioners in applied statistics, quality control, life testing, and reliability. With its accessible style...

Progress report 1971/72

International Nuclear Information System (INIS)

1972-01-01

The progress report comprises reports from interdisciplinary task groups on radiation protection, isotope application and radiation measurement technique, microscopy, linear accelerators, process computers, biophysics and nuclear physics. The last task group reports on work with the electron linear accelerator, nuclear spectroscopy, neutron physics, work with polarized particles, and experiments with the GSI heavy ion accelerator. (orig./AK) [de

BARC progress report - 1998

Energy Technology Data Exchange (ETDEWEB)

Kalyane, V L [comp.; Library and Information Services Div., Bhabha Atomic Research Centre, Mumbai (India)

1999-04-01

This report is a compilation of the progress in various major activities and Research and Development programmes of the different Divisions of the Bhabha Atomic Research Centre, Mumbai. The list of publications and papers presented at the various conferences, symposia, workshops and papers published in journal by the staff members of the Divisions are also given. (author) figs., tabs.

BARC progress report - 1998

International Nuclear Information System (INIS)

Kalyane, V.L.

1999-04-01

This report is a compilation of the progress in various major activities and Research and Development programmes of the different Divisions of the Bhabha Atomic Research Centre, Mumbai. The list of publications and papers presented at the various conferences, symposia, workshops and papers published in journal by the staff members of the Divisions are also given. (author)

MCNP Progress & Performance Improvements

Energy Technology Data Exchange (ETDEWEB)

Brown, Forrest B. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Bull, Jeffrey S. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Rising, Michael Evan [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

2015-04-14

Twenty-eight slides give information about the work of the US DOE/NNSA Nuclear Criticality Safety Program on MCNP6 under the following headings: MCNP6.1.1 Release, with ENDF/B-VII.1; Verification/Validation; User Support & Training; Performance Improvements; and Work in Progress. Whisper methodology will be incorporated into the code, and run speed should be increased.

Progress Report 1985-1986

International Nuclear Information System (INIS)

1987-01-01

The research directions in the Physics Institute of Universidade Federal do Rio Grande do Sul are presented. The progress reports cavied out in the follow areas are presented: perturbed angular correlation; Moessbauer spectroscopy; ion implantation; magnetism and electronic transport; microelectronics; condensed matter theory; quantum field theory; plasma physics; nuclear physics; astronomy and astrophysics; and instrumentation. (M.C.K.) [pt

BARC progress report - 1997

Energy Technology Data Exchange (ETDEWEB)

Kalyane, V L [comp.; Library and Information Services Div., Bhabha Atomic Research Centre, Mumbai (India)

1998-07-01

This report is a compilation of the progress in various major activities and Research and Development programmes of the different Divisions of the Bhabha Atomic Research Centre, Mumbai. The list of publications and papers presented at the various conferences, symposia, workshops and papers published in journal by the staff members of the Divisions are also given. (author) figs., tabs.

BARC progress report - 1997

International Nuclear Information System (INIS)

Kalyane, V.L.

1998-07-01

This report is a compilation of the progress in various major activities and Research and Development programmes of the different Divisions of the Bhabha Atomic Research Centre, Mumbai. The list of publications and papers presented at the various conferences, symposia, workshops and papers published in journal by the staff members of the Divisions are also given. (author)

Progress Toward Heavy Ion IFE

International Nuclear Information System (INIS)

Meier, W.R.; Logan, B.G.; Waldron, W.L.; Sabbi, G.L.; Callahan-Miller, D.A.; Peterson, P.F.; Goodin, D.T.

2002-01-01

Successful development of Heavy Ion Fusion (HIF) will require scientific and technology advances in areas of targets, drivers and chambers. Design work on heavy ion targets indicates that high gain (60-130) may be possible with a -3-6 MJ driver depending on the ability to focus the beams to small spot sizes. Significant improvements have been made on key components of heavy ion drivers, including sources, injectors, insulators and ferromagnetic materials for long-pulse induction accelerator cells, solid-state pulsers, and superconducting quadrupole magnets. The leading chamber concept for HIF is the thick-liquid-wall HYLEE-II design, which uses an array of flibe jets to protect chamber structures from x-ray, debris, and neutron damage. Significant progress has been made in demonstrating the ability to create and control the types of flow needed to form the protective liquid blanket. Progress has also been made on neutron shielding for the final focus magnet arrays with predicted lifetimes now exceeding the life of the power plant. Safety analyses have been completed for the HYLEE-II design using state-of-the-art codes. Work also continues on target fabrication and injection for HE. A target injector experiment capable of > 5 Hz operation has been designed and construction will start in 2002. Methods for mass production of hohlraum targets are being evaluated with small-scale experiments and analyses. Progress in these areas will be reviewed

Progress toward heavy-ion IFE

International Nuclear Information System (INIS)

Meier, W.R.; Logan, B.G.; Waldron, W.L.; Sabbi, G.-L.; Callahan, D.A.; Peterson, P.F.; Goodin, D.T.

2002-01-01

Successful development of heavy-ion fusion (HIF) will require scientific and technology advances in areas of targets, drivers and chambers. Design work on heavy-ion targets indicates that high gain (60-130) may be possible with a ∼3-6 MJ driver depending on the ability to focus the beams to small spot sizes. Significant improvements have been made on key components of heavy-ion drivers, including sources, injectors, insulators and ferromagnetic materials for long-pulse induction accelerator cells, solid-state pulsers, and superconducting quadrupole magnets. The leading chamber concept for HIF is the thick-liquid-wall HYLIFE-II design, which uses an array of flibe jets to protect chamber structures from X-ray, debris, and neutron damage. Significant progress has been made in demonstrating the ability to create and control the types of flow needed to form the protective liquid blanket. Progress has also been made on neutron shielding for the final focus magnet arrays with predicted lifetimes now exceeding the life of the power plant. Safety analyses have been completed for the HYLIFE-II design using state-of-the-art codes. Work also continues on target fabrication and injection for HIF. A target injector experiment capable of >5 Hz operation has been designed and construction will start in 2002. Methods for mass-production of hohlraum targets are being evaluated with small-scale experiments and analyses. Progress in these areas will be reviewed

Defining active progressive multiple sclerosis

DEFF Research Database (Denmark)

Sellebjerg, Finn; Börnsen, Lars; Ammitzbøll, Cecilie

2017-01-01

BACKGROUND: It is unknown whether disease activity according to consensus criteria (magnetic resonance imaging activity or clinical relapses) associate with cerebrospinal fluid (CSF) changes in progressive multiple sclerosis (MS). OBJECTIVE: To compare CSF biomarkers in active and inactive...

Different Molecular Mechanisms Mediate Direct or Glia-Dependent Prion Protein Fragment 90-231 Neurotoxic Effects in Cerebellar Granule Neurons.

Science.gov (United States)

Thellung, Stefano; Gatta, Elena; Pellistri, Francesca; Villa, Valentina; Corsaro, Alessandro; Nizzari, Mario; Robello, Mauro; Florio, Tullio

2017-10-01

Glia over-stimulation associates with amyloid deposition contributing to the progression of central nervous system neurodegenerative disorders. Here we analyze the molecular mechanisms mediating microglia-dependent neurotoxicity induced by prion protein (PrP)90-231, an amyloidogenic polypeptide corresponding to the protease-resistant portion of the pathological prion protein scrapie (PrP Sc ). PrP90-231 neurotoxicity is enhanced by the presence of microglia within neuronal culture, and associated to a rapid neuronal [Ca ++ ] i increase. Indeed, while in "pure" cerebellar granule neuron cultures, PrP90-231 causes a delayed intracellular Ca ++ entry mediated by the activation of NMDA receptors; when neuron and glia are co-cultured, a transient increase of [Ca ++ ] i occurs within seconds after treatment in both granule neurons and glial cells, then followed by a delayed and sustained [Ca ++ ] i raise, associated with the induction of the expression of inducible nitric oxide synthase and phagocytic NADPH oxidase. [Ca ++ ] i fast increase in neurons is dependent on the activation of multiple pathways since it is not only inhibited by the blockade of voltage-gated channel activity and NMDA receptors but also prevented by the inhibition of nitric oxide and PGE 2 release from glial cells. Thus, Ca ++ homeostasis alteration, directly induced by PrP90-231 in cerebellar granule cells, requires the activation of NMDA receptors, but is greatly enhanced by soluble molecules released by activated glia. In glia-enriched cerebellar granule cultures, the activation of inducible nitric oxide (iNOS) and NADPH oxidase represents the main mechanism of toxicity since their pharmacological inhibition prevented PrP90-231 neurotoxicity, whereas NMDA blockade by D(-)-2-amino-5-phosphonopentanoic acid is ineffective; conversely, in pure cerebellar granule cultures, NMDA blockade but not iNOS inhibition strongly reduced PrP90-231 neurotoxicity. These data indicate that amyloidogenic peptides

Chirality and chiroptical properties of amyloid fibrils.

Science.gov (United States)

Dzwolak, Wojciech

2014-09-01

Chirality of amyloid fibrils-linear beta-sheet-rich aggregates of misfolded protein chains-often manifests in morphological traits such as helical twist visible in atomic force microscopy and in chiroptical properties accessible to vibrational circular dichroism (VCD). According to recent studies the relationship between molecular chirality of polypeptide building blocks and superstructural chirality of amyloid fibrils may be more intricate and less deterministic than previously assumed. Several puzzling experimental findings have put into question earlier intuitive ideas on: 1) the bottom-up chirality transfer upon amyloidogenic self-assembly, and 2) the structural origins of chiroptical properties of protein aggregates. For example, removal of a single amino acid residue from an amyloidogenic all-L peptide was shown to reverse handedness of fibrils. On the other hand, certain types of amyloid aggregates revealed surprisingly strong VCD spectra with the sign and shape dependent on the conditions of fibrillation. Hence, microscopic and chiroptical studies have highlighted chirality as one more aspect of polymorphism of amyloid fibrils. This brief review is intended to outline the current state of research on amyloid-like fibrils from the perspective of their structural and superstructural chirality and chiroptical properties. © 2014 Wiley Periodicals, Inc.

Infrastructures of progress and dispossession

DEFF Research Database (Denmark)

Andersen, Astrid Oberborbeck

2016-01-01

and organizational infrastructural arrangements, it is argued, can open up for understanding how local and beyond-local processes tangle in complex ways and are productive of new subjectivities; how relations are reconfi gured in neoliberal landscapes of progress and dispossession. Such an approach makes evident how...... to reposition small and medium-scale farmers as backward. Th is article analyzes how farmers struggle to fi nd their place within a neoliberal urban ecology where diff erent conceptions of what constitutes progress in contemporary Peru infl uence the landscape. Using an analytical lens that takes material...... and organizational infrastructures and practices into account, and situates these in specifi c historical processes, the article argues that farmers within the urban landscape of Arequipa struggle to reclaim land and water, and reassert a status that they experience to be losing. Such a historical focus on material...

Progress of MICE RFCC Module

Energy Technology Data Exchange (ETDEWEB)

Li, D.; Bowring, D.; DeMello, A.; Gourlay, S.; Green, M.; Li, N.; Niinikoski, T.; Pan, H.; Prestemon, S.; Virostek, S.; Zisman, M.; Bross, A.; Carcagno, R.; Kashikhin, V.; Sylvester, C.; Chen, A. B.; Guo, Bin; Li, Liyi; Xu, Fengyu; Cao, Y.; Sun, S.; Wang, Li; Yin, Lixin; Luo, Tianhuan; Summers, Don; Smith, B.; Radovinsky, A.; Zhukovsky, A.; Kaplan, D.

2012-05-20

Recent progress on the design and fabrication of the RFCC (RF and superconducting Coupling Coil) module for the international MICE (Muon Ionization Cooling Experiment) are reported. The MICE ionization cooling channel has two RFCC modules, each having four 201- MHz normal conducting RF cavities surrounded by one superconducting coupling coil (solenoid) magnet. The magnet is designed to be cooled by three cryocoolers. Fabrication of the RF cavities is complete; preparation for the cavity electro-polishing, low power RF measurements, and tuning are in progress at Lawrence Berkeley National Laboratory (LBNL). Fabrication of the cold mass of the first coupling coil magnet has been completed in China and the cold mass arrived at LBNL in late 2011. Preparations for testing the cold mass are currently under way at Fermilab. Plans for the RFCC module assembly and integration are being developed and are described.

Progress in optics

CERN Document Server

Wolf, Emil

2009-01-01

In the fourty-seven years that have gone by since the first volume of Progress in Optics was published, optics has become one of the most dynamic fields of science. The volumes in this series which have appeared up to now contain more than 300 review articles by distinguished research workers, which have become permanent records for many important developments.- Backscattering and Anderson localization of light- Advances in oliton manipulation in optical lattices- Fundamental quantum noise in optical amplification- Invisibility cloaks

VIBRONIC PROGRESSIONS IN SEVERAL DIFFUSE INTERSTELLAR BANDS

International Nuclear Information System (INIS)

Duley, W. W.; Kuzmin, Stanislav

2010-01-01

A number of vibronic progressions based on low-energy vibrational modes of a large molecule have been found in the diffuse interstellar band (DIB) spectrum of HD 183143. Four active vibrational modes have been identified with energies at 5.18 cm -1 , 21.41 cm -1 , 31.55 cm -1 , and 34.02 cm -1 . The mode at 34.02 cm -1 was previously recognized by Herbig. Four bands are associated with this molecule, with origins at 6862.61 A, 6843.64 A, 6203.14 A, and 5545.11 A (14589.1 cm -1 , 14608.08 cm -1 , 16116.41 cm -1 , and 18028.9 cm -1 , respectively). The progressions are harmonic and combination bands are observed involving all modes. The appearance of harmonic, rather than anharmonic, terms in these vibronic progressions is consistent with torsional motion of pendant rings, suggesting that the carrier is a 'floppy' molecule. Some constraints on the type and size of the molecule producing these bands are discussed.

CT assessment of progression in pulmonary emphysema

Energy Technology Data Exchange (ETDEWEB)

Satoh, Katashi; Mitani, Masahiro [Kagawa Medical Univ., Miki (Japan); Murota, Makiko (and others)

2002-01-01

The purpose of this study was to assess the progression of pulmonary emphysema (PE) using CT. We reviewed the records of 25 cases (all male smokers and age range of 36-85 years) in whom progression of PE was recognized using CT scanning. PE was diagnosed by the presence of low attenuation areas on CT scan. PE was divided into 2 subtypes: centrilobular emphysema (CLE) and paraseptal emphysema (PSE). There were 8 younger cases less than 50s. With respect to smoking habit, 6 cases had 1 pack per day at maximum whereas the remaining 19 cases had more over than 1.5 packs per day. Interval periods of observation were from 8 months minimum to 10 years maximum. PE, of both CLE and PSE subtype, was recognized even in younger cases less than 40 years of age, and progressed with cigarette consumption even a minimum during 8 months periods of observation. (author)

Progress and prospects for indirect drive ICF

International Nuclear Information System (INIS)

Lindl, J.D.

1992-08-01

During the past few years, a great deal of progress has been made toward demonstrating the requirements for ignition and high gain ICF targets. Because of this progress, the 1990 National Academy of Science (NAS) and Fusion Policy Advisory Committee (FPAC) reviews recommended that the US National ICF Program focus on the physics of ignition. Subject to successful completion of a series of experiments to be carried out on the Nova laser at Lawrence Livermore National Laboratory (LLNL), these reviews advocated construction of a 1 to 2 MJ glass laser, whose purpose would be demonstration of ignition and modest-gain ICF targets within about a decade. The LLNL proposal for this National Ignition Facility, which was endorsed by the NAS and FPAC as the most timely and cost effective path to this goal, is referred to as the ''Nova Upgrade.'' This paper reviews recent progress on the Nova laser and the performance expected with the Nova Upgrade

Pakistan strong industrial base urged for economic progress

CERN Multimedia

2001-01-01

A conference organized by Pakistan Nuclear Society urged that Pakistan should develop a strong industrial base and capability to export equipment for economic progress. The chairmen of PAEC pointed out that Pakistan is already showing remarkable progress in export of science-related equipment to CERN. He also asked scientists to wage a war against Pakistans inability to acquire indigenous technology (1 page).

Development of indigenous irradiator - current progress and challenges

International Nuclear Information System (INIS)

Anwar A Rahman; Mohd Arif Hamzah; Muhd Nor Atan; Aznor Hassan; Fadil Ismail; Julia A Karim; Rosli Darmawan

2009-01-01

The development of indigenous irradiator is one of Prototype Development Center main project to support Nuclear Malaysia services. Three (3) projects have been identified and currently the status is in final stage of design. There are some issues and challenges encountered, which delayed the project progress. The paper will discuss the current progress of development and challenges faced in designing the irradiator. (Author)

Study of progressive depigmentation of dog′s muzzle

Directory of Open Access Journals (Sweden)

Shah K

1991-01-01

Full Text Available A new animal model is developed using dog′s muzzle to demonstrate progressive depigmen-tation after birth. Dog′s muzzle is heavily pigmented with pigment melanin and looks black in colour. Progressive depigmentation was observed two months after birth in a pup born with a depigmented mucous membrane of the mouth and lips. This resembles the vitiligo of humans.

Gatlinburg conference: barometer of progress in analytical chemistry

International Nuclear Information System (INIS)

Shults, W.D.

1981-01-01

Much progress has been made in the field of analytical chemistry over the past twenty-five years. The AEC-ERDA-DOE family of laboratories contributed greatly to this progress. It is not surprising then to find a close correlation between program content of past Gatlinburg conferences and developments in analytical methodology. These conferences have proved to be a barometer of technical status

Radiotherapy for local progression in patients with hormone-refractory prostate cancer

International Nuclear Information System (INIS)

Furuya, Yuzo; Akakura, Koichiro; Akimoto, Susumu; Ichikawa, Tomohiko; Ito, Haruo

1999-01-01

The aim of the present study was to investigate the effect of radiotherapy on the local progression of hormone-refractory prostate cancer. From 1986 to 1995, 38 patients were diagnosed with local progression without distant progression after hormonal therapy at Chiba University Hospital. Eleven cases were treated with irradiation for local progression. External beam irradiation was delivered to the prostate at a dose of 50-66.6 Gy. In patients treated with radiotherapy, the duration from initial treatment to local recurrence was 6-80 months (mean±SD: 33.9±22.9 months). The follow-up period after irradiation was 7-64 months (mean±SD: 25.4±18.8 months). Three and 5 year cause-specific survival rates from radiotherapy were 46.2 and 23.1%, respectively. Radiotherapy had a marked effect on symptoms associated with local progression and no patients suffered from the symptoms after the radiotherapy. Complications of radiotherapy were limited. In patients with hormone refractory local progression without distant progression, low morbidity, low mortality radiotherapy offers a variable therapy to other palliative treatments because radiotherapy is able to control local symptoms for a long period of time. (author)

Progress on axicell MFTF-B superconducting magnet systems

International Nuclear Information System (INIS)

Wang, S.T.; Kozman, T.A.; Hanson, C.L.; Shimer, D.W.; VanSant, J.H.; Zbasnik, J.

1983-01-01

Since the entire Mirror Fusion Test Facility (MFTF-B) Magnet System was reconfigured from the original A-cell to an axicell design, much progress has been made on the design, fabrication, and installation planning. The axicell MFTF-B magnet array consists of a total of 26 large superconducting main coils. This paper provides an engineering overview of the progress of these coils. Recent studies on the effects of field errors on the plasma at the recircularizing region (transition coils) show that small field errors will generate large displacements of the field lines. These field errors might enhance radial electron heat transport and deteriorate the plasma confinement. Therefore, 16 superconducting trim coils have been designed to correct the coil misalignments. Progress of the trim coils are reported also

Communication of nuclear data progress: No.15 (1996)

Energy Technology Data Exchange (ETDEWEB)

NONE

1996-06-01

Communication of Nuclear Data Progress (CNDP) is set up by Chinese Nuclear DATA Center. This is the 15th issue. The nuclear data achievements and progress in China during the last year are presented. It mainly includes: the measurements of the energy spectrum and angular distributions of protons from stainless steel bombarded by 14.6 MeV neutrons, theoretical calculations of {sup 59}Co and {sup 90}Zr neutron reaction data, the method and program CABEI for adjusting consistency between natural and its isotope data, {sup 58,60,61,62,64,Nat}Ni(n, p), {sup 59}Co, {sup 90}Zr(n,x) and {sup 84}Rb decay data, the status of CENDL-2.1 and progress on Chinese Evaluated Nuclear Parameter Library.

Design of non-aggregating variants of Aβ peptide

Energy Technology Data Exchange (ETDEWEB)

Caine, Joanne M., E-mail: jo.caine@csiro.au [CSIRO Materials Science and Engineering, 343 Royal Parade, Parkville, Victoria 3052 (Australia); Preventative Health Flagship, 343 Royal Parade, Parkville, Victoria 3052 (Australia); CRC for Mental Health, Level 2, 161 Barry Street, Carlton South, Victoria 3053 (Australia); Churches, Quentin; Waddington, Lynne [CSIRO Materials Science and Engineering, 343 Royal Parade, Parkville, Victoria 3052 (Australia); Preventative Health Flagship, 343 Royal Parade, Parkville, Victoria 3052 (Australia); Nigro, Julie; Breheney, Kerry [CSIRO Materials Science and Engineering, 343 Royal Parade, Parkville, Victoria 3052 (Australia); Preventative Health Flagship, 343 Royal Parade, Parkville, Victoria 3052 (Australia); CRC for Mental Health, Level 2, 161 Barry Street, Carlton South, Victoria 3053 (Australia); Masters, Colin L. [CRC for Mental Health, Level 2, 161 Barry Street, Carlton South, Victoria 3053 (Australia); Florey Institute for Neuroscience and Mental Health, 30 Royal Parade, Parkville, Victoria 3052 (Australia); Nuttall, Stewart D. [CSIRO Materials Science and Engineering, 343 Royal Parade, Parkville, Victoria 3052 (Australia); Preventative Health Flagship, 343 Royal Parade, Parkville, Victoria 3052 (Australia); CRC for Mental Health, Level 2, 161 Barry Street, Carlton South, Victoria 3053 (Australia); Streltsov, Victor A., E-mail: victor.streltsov@csiro.au [CSIRO Materials Science and Engineering, 343 Royal Parade, Parkville, Victoria 3052 (Australia); Preventative Health Flagship, 343 Royal Parade, Parkville, Victoria 3052 (Australia); CRC for Mental Health, Level 2, 161 Barry Street, Carlton South, Victoria 3053 (Australia)

2014-10-24

Highlights: • Non-aggregating, non-toxic variants of Aβ peptide were designed using Aβ structure. • Mutations reduce aggregation by stabilising Aβ into small non-toxic oligomers. • Identification of these residues will assist the design of future therapeutic peptides. - Abstract: Self association of the amyloid-β (Aβ{sub 42}) peptide into oligomers, high molecular weight forms, fibrils and ultimately neuritic plaques, has been correlated with progressive cognitive decline in Alzheimer’s disease. Thus, insights into the drivers of the aggregation pathway have the capacity to significantly contribute to our understanding of disease mechanism. Functional assays and a three-dimensional crystal structure of the P3 amyloidogenic region 18–41 of Aβ were used to identify residues important in self-association and to design novel non-aggregating variants of the peptide. Biophysical studies (gel filtration, SDS–PAGE, dynamic light scattering, thioflavin T assay, and electron microscopy) demonstrate that in contrast to wild type Aβ these targeted mutations lose the ability to self-associate. Loss of aggregation also correlates with reduced neuronal toxicity. Our results highlight residues and regions of the Aβ peptide important for future targeting agents aimed at the amelioration of Alzheimer’s disease.

Treatment with Akebia Saponin D Ameliorates Aβ1–42-Induced Memory Impairment and Neurotoxicity in Rats

Directory of Open Access Journals (Sweden)

Yongde Chen

2016-03-01

Full Text Available Amyloid-β peptide (Aβ is known to be directly associated with the progressive neuronal death observed in Alzheimer’s disease (AD. However, effective neuroprotective approaches against Aβ neurotoxicity are still unavailable. In the present study, we investigated the protective effects of Akebia saponin D (ASD, a typical compound isolated from the rhizome of Dipsacus asper Wall, on Aβ1–42-induced impairment of learning and memory formation and explored the probable underlying molecular mechanisms. We found that treatment with ASD (30, 90 or 270 mg/kg significantly ameliorated impaired spatial learning and memory in intracerebroventricularly (ICV Aβ1–42-injected rats, as evidenced by a decrease tendency in escape latency during acquisition trials and improvement in exploratory activities in the probe trial in Morris water maze (MWM. Further study showed that ASD reversed Aβ1–42-induced accumulation of Aβ1–42 and Aβ1–40 in the hippocampus through down-regulating the expression of BACE and Presenilin 2 accompanied with increased the expression of TACE, IDE and LRP-1. Taken together, our findings suggested that ASD exerted therapeutic effects on Aβ-induced cognitive deficits via amyloidogenic pathway.

National-level progress on adaptation

NARCIS (Netherlands)

Lesnikowski, A.; Ford-Robertson, J.; Biesbroek, G.R.; Berrang-Ford, L.; Heymann, S.J.

2016-01-01

It is increasingly evident that adaptation will figure prominently in the post-2015 United Nations climate change agreement. As adaptation obligations under the United Nations Framework Convention on Climate Change evolve, more rigorous approaches to measuring adaptation progress among parties will

[Various pathways leading to the progression of chronic liver diseases].

Science.gov (United States)

Egresi, Anna; Lengyel, Gabriella; Somogyi, Anikó; Blázovics, Anna; Hagymási, Krisztina

2016-02-21

As the result of various effects (viruses, metabolic diseases, nutritional factors, toxic agents, autoimmune processes) abnormal liver function, liver steatosis and connective tissue remodeling may develop. Progression of this process is complex including various pathways and a number of factors. The authors summarize the factors involved in the progression of chronic liver disease. They describe the role of cells and the produced inflammatory mediators and cytokines, as well as the relationship between the disease and the intestinal flora. They emphasize the role of oxidative stress, mitochondrial dysfunction and cell death in disease progression. Insulin resistance and micro-elements (iron, copper) in relation to liver damage are also discussed, and genetic and epigenetic aspects underlying disease progression are summarized. Discovery of novel treatment options, assessment of the effectiveness of treatment, as well as the success and proper timing of liver transplantation may depend on a better understanding of the process of disease progression.

Empirical Refinements of a Molecular Genetics Learning Progression: The Molecular Constructs

Science.gov (United States)

Todd, Amber; Kenyon, Lisa

2016-01-01

This article describes revisions to four of the eight constructs of the Duncan molecular genetics learning progression [Duncan, Rogat, & Yarden, (2009)]. As learning progressions remain hypothetical models until validated by multiple rounds of empirical studies, these revisions are an important step toward validating the progression. Our…

An Argument for Formative Assessment with Science Learning Progressions

Science.gov (United States)

Alonzo, Alicia C.

2018-01-01

Learning progressions--particularly as defined and operationalized in science education--have significant potential to inform teachers' formative assessment practices. In this overview article, I lay out an argument for this potential, starting from definitions for "formative assessment practices" and "learning progressions"…

Progression from acute to chronic pancreatitis: prognostic factors, mortality, and natural course.

Science.gov (United States)

Nøjgaard, Camilla; Becker, Ulrik; Matzen, Peter; Andersen, Jens Rikardt; Holst, Claus; Bendtsen, Flemming

2011-11-01

Knowledge of the natural course of acute pancreatitis (AP) and risk of progression to chronic pancreatitis (CP) is limited. The aims were to describe: (1) the incidence of progression from AP to CP, (2) prognostic factors for progression, and (3) the natural course and mortality of progressive AP. During 1977 to 1982, patients admitted to hospitals in Copenhagen with a diagnosis of AP or CP were included in a prospective cohort and followed up by the Danish registries in 2008. The subcohort analyses comprised 352 AP patients. Progressive AP was found in 85 patients (24.1%) during follow-up; 48.2% developed from alcoholic AP, 47.0% from idiopathic AP, and 4.8% from other causes. The mortality rate for patients with progressive AP was 2.7 times higher than in patients with nonprogressive acute pancreatitis, and 5.3 to 6.5 times higher than in the background population. In Cox regression analyses corrected for age, only smoking was of significance for the progression from AP to CP. Acute pancreatitis can progress to CP, not only from alcoholic but also from nonalcoholic AP. Smoking was the strongest risk factor associated with progression. The mortality rate for these patients was 5 to 6 times the mortality rate in the population.

Identification of genetic variants associated with Huntington's disease progression

DEFF Research Database (Denmark)

Hensman Moss, Davina J; Pardiñas, Antonio F; Langbehn, Douglas

2017-01-01

indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008-11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers...... in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression......BACKGROUND: Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate...

Progressive multiple sclerosis, cognitive function, and quality of life.

Science.gov (United States)

Højsgaard Chow, Helene; Schreiber, Karen; Magyari, Melinda; Ammitzbøll, Cecilie; Börnsen, Lars; Romme Christensen, Jeppe; Ratzer, Rikke; Soelberg Sørensen, Per; Sellebjerg, Finn

2018-02-01

Patients with progressive multiple sclerosis (MS) often have cognitive impairment in addition to physical impairment. The burden of cognitive and physical impairment progresses over time, and may be major determinants of quality of life. The aim of this study was to assess to which degree quality of life correlates with physical and cognitive function in progressive MS. This is a retrospective study of 52 patients with primary progressive ( N  = 18) and secondary progressive MS ( N  = 34). Physical disability was assessed using the Expanded Disability Status Scale, Timed 25 Foot Walk (T25FW) test and 9-Hole Peg Test (9HPT). Cognitive function was assessed using Symbol Digit Modalities Test (SDMT), Paced Auditory Serial Addition Test, and Trail Making Test B (TRAIL-B). In addition, quality of life was assessed by the Short Form 36 (SF-36) questionnaire. Only measures of cognitive function correlated with the overall SF-36 quality of life score and the Mental Component Summary score from the SF-36. The only physical measure that correlated with a measure of quality of life was T25FW test, which correlated with the Physical Component Summary from the SF-36. We found no other significant correlations between the measures of cognitive function and the overall physical measures but interestingly, we found a possible relationship between the 9HPT score for the nondominant hand and the SDMT and TRAIL-B. Our findings support inclusion of measures of cognitive function in the assessment of patients with progressive MS as these correlated closer with quality of life than measures of physical impairment.

Chance, purpose, and progress in evolution and christianity.

Science.gov (United States)

Mix, Lucas J; Masel, Joanna

2014-08-01

Evolutionary biology has a complex relationship with ideas of chance, purpose, and progress. Probability plays a subtle role; strikingly, founding figures in statistics were motivated by evolutionary questions. The findings of evolutionary biology have been used both in support of narratives of progress, and in their deconstruction. Likewise, professional biologists bring to their scientific work a set of preconceptions about chance and progress, grounded in their philosophical, religious, and/or political views. From the religious side, questions of purpose are ever-present. We explore this interplay in five broad categories: chance, progress, intelligence, eugenics, and the evolution of religious practices, each the subject of a semester long symposium. The intellectual influence of evolutionary biology has had a broad societal impact in these areas. Based on our experience, we draw attention to a number of relevant facts that, while accepted by experts in their respective fields, may be unfamiliar outside them. We list common areas of miscommunication, including specific examples and discussing causes: sometimes semantics and sometimes more substantive knowledge barriers. We also make recommendations for those attempting similar dialogue. © 2014 The Author(s). Evolution © 2014 The Society for the Study of Evolution.

Introducing errors in progress ratios determined from experience curves

NARCIS (Netherlands)

van Sark, W.G.J.H.M.

2008-01-01

Progress ratios (PRs) derived from historical data in experience curves are used for forecasting development of many technologies as a means to model endogenous technical change in for instance climate–economy models. These forecasts are highly sensitive to uncertainties in the progress ratio. As a

What is progressive about Nigerian personal income tax? | Egbon ...

African Journals Online (AJOL)

This paper conceptually critiques the progressivity of the current personal income tax in Nigeria by drawing on the equity concept of taxation vis-à-visincome redistributionandtaxpayers' ability to pay tax. Whilst the study acknowledges the presumed progressivity and income redistribution notions embedded within the ...

Exercise training and the progression of chronic renal failure

DEFF Research Database (Denmark)

Eidemak, I; Haaber, A B; Feldt-Rasmussen, B

1997-01-01

The possible beneficial effect of regular exercise training on the progression of chronic renal failure was studied in a prospective randomized controlled study. Thirty patients with a median glomerular filtration rate (GFR) of 25 ml/(min.1.73 m2) (range 10-43) were randomized to physical training...... the rate of progression judged by the slope of GFR versus time plot was equal in the two groups. Hence, the beneficial effect of exercise training, earlier observed in rat studies, could not be reproduced in our patients. Physical exercise had no untoward effect on progression of renal disease....

APOL1 Oligomerization as the Key Mediator of Kidney Disease in African Americans

Science.gov (United States)

2016-10-01

protein in an amyloid-like process. We are testing this hypothesis in in vitro systems, cells, and model systems using molecular biology, biochemistry ...human kidney biopsy specimens using molecular biology, biochemistry , protein chemistry, and microscopy-based approaches. 2. KEYWORDS: Kidney, ESRD...presence of Thioflavin T a. Test both (1) APOL1 holoprotein and (2) amyloidogenic ApoL1 fragments b. Repeat, varying concentration, time, pH , and

20 CFR 411.180 - What is timely progress toward self-supporting employment?

Science.gov (United States)

2010-04-01

... Who Are Using a Ticket Introduction § 411.180 What is timely progress toward self-supporting... the previous 12-month progress certification period. In computing any 12-month progress certification...

Forecasting of Radiation Belts: Results From the PROGRESS Project.

Science.gov (United States)

Balikhin, M. A.; Arber, T. D.; Ganushkina, N. Y.; Walker, S. N.

2017-12-01

Forecasting of Radiation Belts: Results from the PROGRESS Project. The overall goal of the PROGRESS project, funded in frame of EU Horizon2020 programme, is to combine first principles based models with the systems science methodologies to achieve reliable forecasts of the geo-space particle radiation environment.The PROGRESS incorporates three themes : The propagation of the solar wind to L1, Forecast of geomagnetic indices, and forecast of fluxes of energetic electrons within the magnetosphere. One of the important aspects of the PROGRESS project is the development of statistical wave models for magnetospheric waves that affect the dynamics of energetic electrons such as lower band chorus, hiss and equatorial noise. The error reduction ratio (ERR) concept has been used to optimise the set of solar wind and geomagnetic parameters for organisation of statistical wave models for these emissions. The resulting sets of parameters and statistical wave models will be presented and discussed. However the ERR analysis also indicates that the combination of solar wind and geomagnetic parameters accounts for only part of the variance of the emissions under investigation (lower band chorus, hiss and equatorial noise). In addition, advances in the forecast of fluxes of energetic electrons, exploiting empirical models and the first principles IMPTAM model achieved by the PROGRESS project is presented.

John Woolman and Ethical Progress in Kitcher's Pragmatic Naturalism.

Science.gov (United States)

Barresi, John

2017-01-01

The development of John Woolman’s views on slavery plays an important evidentiary role in Philip Kitcher’s recent book, The ethical project (Kitcher 2011). In this work Kitcher takes what he calls a “pragmatic naturalist” approach to ethics and claims that the discovery of ethical truth plays no role in the emergence of ethical progress. To support his view, he argues that Woolman’s contribution was not due to his discovery of an ethical truth about slavery, not previously known, but due to his sensitivity to slavery and his influence on others, which contributed to collective progressive change in moral norms involving slavery. While not disputing Kitcher’s ethical theory, I argue that personal discoveries of a moral psychological nature made by Woolman served both as insights and motivations for his contribution. Thus, even if there are no such things as independent ethical truths that can be discovered by individuals, a fully naturalistic approach to ethical progress requires that we make room not only for group-level progressive evolution of norms, but also for individual discoveries of a moral psychological nature that can sometimes cause an individual to play a significant initiating role in progressive ethical transitions that occur at a group level.

Chemistry Division: progress report (1983-84)

International Nuclear Information System (INIS)

Shastri, L.V.; George, A.M.

1985-01-01

This is the seventh progress report of the Chemistry Division covering the two years 1983 and 1984. The main emphasis of the Division continues to be on basic research though spin offs in high technology areas are closely pursued. Laboratory facilities have been considerably augmented during this period. Besides the design and fabrication of a crossed molecular beam chemiluminescence apparatus, a 80 MHz FTNMR and a 5nsec. excimer laser kinetic spectrometer were acquired; a 5nsec. pulsed electron accelerator would be installed in 1985. The research and development projects taken up during the VI Five Year Plan have achieved considerable progress. Only brief accounts of investigations are presented in the report. (author)

ADAPTATION AND PROGRESS THROUGH CHANGE MANAGEMENT

Directory of Open Access Journals (Sweden)

Gabriela MEHEDINTU

2016-12-01

Full Text Available The technological progress, digitization and the explosion of information significantly change how individuals, the business environment, and society act, develop and add value. New, interdisciplinary approaches, constantly adapted and sustainable both at the micro and the macro levels are required. Within a company, change management is a systematic element of the strategic business process and involves the early identification of the opportunity of the employees’ development, courage, commitment and flexibility; under no circumstances should it be seen as a risk and instability factor, as it may be considered in the early stages. The example presented in this article proves that the openness to change and continuous improvement develops advantages, optimizes processes and sustains long-term progress.

Recent progress in power electronic devices

Energy Technology Data Exchange (ETDEWEB)

Ikeda, Yasuhiko; Yatsuo, Tsutomu

1987-02-01

Recent progress and future trends of power semiconductor devices (especially with respect to motor speed control) were described. Conventional discrete devices such as thyristors, bipolar transistors, unipolar transistors and Bi-MOS devices were referenced to. Reference was also made to High Voltage ICs. There has been steady progress with each of these power devices in current carrying capability, voltage blocking capability and switching speed. The Bipolar-MOS integreated device and the High Voltage IC are particularly interesting because their abilities and performances are much enhanced by skillful combination with conventional discrete devices. However, no one device meets all the needs, and it will always be necessary to select the right device for a specific task. (11 figs, 35 refs)

Progression of Dysphagia in Spinocerebellar Ataxia Type 6.

Science.gov (United States)

Isono, Chiharu; Hirano, Makito; Sakamoto, Hikaru; Ueno, Shuichi; Kusunoki, Susumu; Nakamura, Yusaku

2017-06-01

Spinocerebellar ataxia type 6 (SCA6), an autosomal dominant triplet repeat disease, predominantly affects the cerebellum with a late onset and generally good prognosis. Dysphagia is commonly associated with the outcomes of neurodegenerative diseases such as SCA6. Although the characteristics of dysphagia have been rarely reported in SCA6, our previous study indicated that dysphagia is generally milder in SCA6 than in SCA3, another inherited ataxia with multisystem involvement. However, abnormalities in the pharyngeal phase in SCA6 were indistinguishable from those in SCA3, with no explainable reason. To determine the reason, we repeatedly performed videofluoroscopic examinations (VF) in 14 patients with SCA6. The results showed that the gross progression of dysphagia was apparently slow, but four patients had progressive dysphagia at an early disease stage; dysphagia began within 10 years from the onset of ataxia and rapidly progressed. A common clinical feature of the four patients was a significantly older age at the onset of ataxia (74.0 vs. 60.3 years), associated with significantly shorter triplet repeats. This finding surprisingly indicated that patients who had shorter repeats and thereby later onset and potentially better prognoses were at risk for dysphagia-associated problems. Ischemic changes, homozygous mutation, and diabetes mellitus as well as aging might have contributed to the observed progressive dysphagia. We found that conventionally monitored somatosensory evoked potentials at least partly reflected progressive dysphagia. Despite the small study group, our findings suggest that clinicians should carefully monitor dysphagia in patients with SCA6 who are older at disease onset (>60 years).

Brain viscoelasticity alteration in chronic-progressive multiple sclerosis.

Directory of Open Access Journals (Sweden)

Kaspar-Josche Streitberger

Full Text Available INTRODUCTION: Viscoelastic properties indicate structural alterations in biological tissues at multiple scales with high sensitivity. Magnetic Resonance Elastography (MRE is a novel technique that directly visualizes and quantitatively measures biomechanical tissue properties in vivo. MRE recently revealed that early relapsing-remitting multiple sclerosis (MS is associated with a global decrease of the cerebral mechanical integrity. This study addresses MRE and MR volumetry in chronic-progressive disease courses of MS. METHODS: We determined viscoelastic parameters of the brain parenchyma in 23 MS patients with primary or secondary chronic progressive disease course in comparison to 38 age- and gender-matched healthy individuals by multifrequency MRE, and correlated the results with clinical data, T2 lesion load and brain volume. Two viscoelastic parameters, the shear elasticity μ and the powerlaw exponent α, were deduced according to the springpot model and compared to literature values of relapsing-remitting MS. RESULTS: In chronic-progressive MS patients, μ and α were reduced by 20.5% and 6.1%, respectively, compared to healthy controls. MR volumetry yielded a weaker correlation: Total brain volume loss in MS patients was in the range of 7.5% and 1.7% considering the brain parenchymal fraction. All findings were significant (P<0.001. CONCLUSIONS: Chronic-progressive MS disease courses show a pronounced reduction of the cerebral shear elasticity compared to early relapsing-remitting disease. The powerlaw exponent α decreased only in the chronic-progressive stage of MS, suggesting an alteration in the geometry of the cerebral mechanical network due to chronic neuroinflammation.

Environment, safety and health progress assessment manual

International Nuclear Information System (INIS)

1992-12-01

On June 27, 1989, the Secretary of Energy announced a 10-Point Initiative to strengthen environment, safety, and health (ES ampersand H) programs, and waste management activities at DOE production, research, and testing facilities. One of the points involved conducting dent Tiger Team Assessments of DOE operating facilities. The Office of Special independent Projects (OSP), EH-5, in the Office of the Assistant Secretary for Environment, Safety and Health, EH-1, was assigned the responsibility to conduct the Tiger Team Assessments. Through June 1992, a total of 35 Tiger Team Assessments were completed. The Secretary directed that Corrective Action Plans be developed and implemented to address the concerns identified by the Tiger Teams. In March 1991, the Secretary approved a plan for assessments that are ''more focused, concentrating on ES ampersand H management, ES ampersand H corrective actions, self-assessment programs, and root-cause related issues.'' In July 1991, the Secretary approved the initiation of ES ampersand H Progress Assessments, as a followup to the Tiger Team Assessments, and in the continuing effort to institutionalize the self-assessment process and line management accountability in the ES ampersand H areas. This manual documents the processes to be used to perform the ES ampersand H Progress Assessments. It was developed based upon the lessons learned from Tiger Team Assessments, the two pilot Progress Assessments, and Progress Assessments that have been completed. The manual will be updated periodically to reflect lessons learned or changes in policy

Progress on alternative energy resources

Science.gov (United States)

Couch, H. T.

1982-03-01

Progress in the year 1981 toward the development of energy systems suitable for replacing petroleum products combustion and growing in use to fulfill a near term expansion in energy use is reviewed. Coal is noted to be a potentially heavy pollution source, and the presence of environmentally acceptable methods of use such as fluidized-bed combustion and gasification and liquefaction reached the prototype stage in 1981, MHD power generation was achieved in two U.S. plants, with severe corrosion problems remaining unsolved for the electrodes. Solar flat plate collectors sales amounted to 20 million sq ft in 1981, and solar thermal electric conversion systems with central receivers neared completion. Solar cells are progressing toward DOE goals of $.70/peak W by 1986, while wind energy conversion sales were 2000 machines in 1981, and the industry is regarded as maturing. Finally, geothermal, OTEC, and fusion systems are reviewed.

Psychosocial predictors of coronary artery calcification progression in postmenopausal women.

Science.gov (United States)

Low, Carissa A; Matthews, Karen A; Kuller, Lewis H; Edmundowicz, Daniel

2011-01-01

Coronary artery calcification (CAC) has been associated with psychosocial factors in some but not all cross-sectional analyses. The goal of this study was to determine whether positive and negative psychosocial factors prospectively predict CAC progression in postmenopausal women. Participants from the Healthy Women Study who also participated in the Pittsburgh Mind-Body Center protocol (n = 149) completed self-report psychosocial measures before two electron beam computed tomographic scans of CAC separated by an average of 3.3 years. Results of exploratory factor analysis were used to create aggregate psychosocial indices: psychological risk (depressive symptoms, perceived stress, cynicism, and anger-in) and psychosocial resources (optimism, purpose in life, mastery, self-esteem, and social support). The psychological risk index predicted significantly greater CAC progression over 3 years (β = 0.16, p = .035, ΔR(2) = 0.03), whereas the psychosocial resources index was not predictive of CAC progression (β = -0.08, p = .30, ΔR(2) = 0.01). On individual scales, higher scores on cynicism emerged as a significant predictor of CAC progression, along with a trend linking anger-in to atherosclerosis progression. A post hoc analysis showed a significant interaction between cynicism and anger-in (β = 0.20, p = .01, ΔR(2) = 0.03), such that women reporting high levels of both cynicism and anger suppression exhibited the most CAC progression. These findings highlight psychosocial risk factors that may accelerate the progression of subclinical atherosclerosis in older women, suggest the potential importance of examining combinations of psychosocial risk factors, and identify potential targets for psychological interventions to reduce cardiovascular risk.

Human genome program report. Part 1, overview and progress

Energy Technology Data Exchange (ETDEWEB)

NONE

1997-11-01

This report contains Part 1 of a two-part report to reflect research and progress in the U.S. Department of Energy Human Genome Program from 1994 through 1996, with specified updates made just before publication. Part 1 consists of the program overview and report on progress.

Sudden oak death disease progression in oaks and tanoaks

Science.gov (United States)

Brice A. McPherson; Sylvia R. Mori; David L. Wood; Andrew J. Storer; Pavel Svihra; N. Maggi Kelly; Richard B. Standiford

2006-01-01

In March 2000, we established twenty disease progression plots in Marin County to monitor the progress of sudden oak death symptoms in coast live oak (Quercus agrifolia), California black oak (Q. kelloggii), and tanoak (Lithocarpus densiflorus) (McPherson and others 2005). Plots were located to encompass a...

Francis Wayland Parker's Morning Exercise and the Progressive Movement

Science.gov (United States)

Schmitt, Natalie Crohn

2010-01-01

In the progressive era, the distinguished political scientist Robert Putnam explains, progressives invested heavily in "social capital," that is, in the stock of active connections, social networks, shared values, norms of reciprocity, trustworthiness, and friendship that bind people together (Putnam 2000, 395). They were, he argues,…

Anti-amyloid aggregation activity of novel carotenoids: implications for Alzheimer’s drug discovery

Directory of Open Access Journals (Sweden)

Lakey-Beitia J

2017-05-01

Full Text Available Johant Lakey-Beitia,1,2 Deborah Doens,2,3 D Jagadeesh Kumar,4 Enrique Murillo,5 Patricia L Fernandez,3 KS Rao,6 Armando A Durant-Archibold1,5 1Center for Biodiversity and Drug Discovery, Instituto de Investigaciones Científicas y Servicios de Alta Tecnología (INDICASAT AIP, Panama, Republic of Panama; 2Department of Biotechnology, Acharya Nagarjuna University, Guntur, India; 3Center for Molecular and Cellular Biology of Diseases, Instituto de Investigaciones Científicas y Servicios de Alta Tecnología (INDICASAT AIP, Panama, Republic of Panama; 4Department of Biotechnology, Sir M Visvesvaraya Institute of Technology, Bangalore, India; 5Department of Biochemistry, College of Natural, Exact Sciences and Technology, University of Panama, Panama, Republic of Panama; 6Center for Neuroscience, Instituto de Investigaciones Científicas y Servicios de Alta Tecnología (INDICASAT AIP, Panama, Republic of Panama Abstract: Alzheimer’s disease (AD is the leading cause of dementia, affecting approximately 33.5 million people worldwide. Aging is the main risk factor associated with AD. Drug discovery based on nutraceutical molecules for prevention and treatment of AD is a growing topic. In this sense, carotenoids are phytochemicals present mainly in fruits and vegetables with reported benefits for human health. In this research, the anti-amyloidogenic activity of three carotenoids, cryptocapsin, cryptocapsin-5,6-epoxide, and zeaxanthin, was assessed. Cryptocapsin showed the highest bioactivity, while cryptocapsin-5,6-epoxide and zeaxanthin exhibited similar activity on anti-aggregation assays. Molecular modeling analysis revealed that the evaluated carotenoids might follow two mechanisms for inhibiting Aβ aggregation: by preventing the formation of the fibril and through disruption of the Aβ aggregates. Our studies provided evidence that cryptocapsin, cryptocapsin-5,6-epoxide, and zeaxanthin have anti-amyloidogenic potential and could be used for

Information Loss from Technological Progress

International Nuclear Information System (INIS)

Townsend, P D

2014-01-01

Progress in electronics and optics offers faster computers, and rapid communication via the internet that is matched by ever larger and evolving storage systems. Instinctively one assumes that this must be totally beneficial. However advances in software and storage media are progressing in ways which are frequently incompatible with earlier systems and the economics and commercial pressures rarely guarantee total compatibility with earlier systems. Instead, the industries actively choose to force the users to purchase new systems and software. Thus we are moving forward with new technological variants that may have access to only the most recent systems and we will have lost earlier alternatives. The reality is that increased processing speed and storage capacity are matched by an equally rapid decline in the access and survival lifetime of older information. This pattern is not limited to modern electronic systems but is evident throughout history from writing on stone and clay tablets to papyrus and paper. It is equally evident in image systems from painting, through film, to magnetic tapes and digital cameras. In sound recording we have variously progressed from wax discs to vinyl, magnetic tape and CD formats. In each case the need for better definition and greater capacity has forced the earlier systems into oblivion. Indeed proposed interactive music systems could similarly relegate music CDs to specialist collections. The article will track some of the examples and discuss the consequences as well as noting that this information loss is further compounded by developments in language and changes in cultural views of different societies

Information Loss from Technological Progress

Science.gov (United States)

Townsend, P. D.

2014-12-01

Progress in electronics and optics offers faster computers, and rapid communication via the internet that is matched by ever larger and evolving storage systems. Instinctively one assumes that this must be totally beneficial. However advances in software and storage media are progressing in ways which are frequently incompatible with earlier systems and the economics and commercial pressures rarely guarantee total compatibility with earlier systems. Instead, the industries actively choose to force the users to purchase new systems and software. Thus we are moving forward with new technological variants that may have access to only the most recent systems and we will have lost earlier alternatives. The reality is that increased processing speed and storage capacity are matched by an equally rapid decline in the access and survival lifetime of older information. This pattern is not limited to modern electronic systems but is evident throughout history from writing on stone and clay tablets to papyrus and paper. It is equally evident in image systems from painting, through film, to magnetic tapes and digital cameras. In sound recording we have variously progressed from wax discs to vinyl, magnetic tape and CD formats. In each case the need for better definition and greater capacity has forced the earlier systems into oblivion. Indeed proposed interactive music systems could similarly relegate music CDs to specialist collections. The article will track some of the examples and discuss the consequences as well as noting that this information loss is further compounded by developments in language and changes in cultural views of different societies.

'Committee 1540': last progress report - News note

International Nuclear Information System (INIS)

Hautecouverture, Benjamin

2007-01-01

The Committee 1540 is in charge of the application of the resolution 1540 of the UN Security Council, and the author briefly presents and comments the content of the last progress report issued by this committee in November 2007. This progress report analyses the situation of the resolution in terms of implementation (number of reports and additional information documents, non reporting states and their location). The author outlines some institutional handicaps, notably the lack of power of control of the Committee for a better application of the resolution

Determinants of health: a progressive political platform.

Science.gov (United States)

Terris, M

1994-01-01

This paper is based on the statement in the Ottawa Charter for Health Promotion that "The fundamental conditions and resources for health are peace, shelter, education, food, income, a stable eco-system, sustainable resources, social justice and equity. Improvement in health requires a secure foundation in these basic prerequisites." It attempts to formulate a progressive political platform for a number of these prerequisites, offering a series of recommendations regarding education, employment, income, and housing, and urging that the proposed programs be funded by progressive taxation and major reductions in the military budget.

Evasion of Cell Senescence Leads to Medulloblastoma Progression

Directory of Open Access Journals (Sweden)

Lukas Tamayo-Orrego

2016-03-01

Full Text Available How brain tumors progress from precancerous lesions to advanced cancers is not well understood. Using Ptch1+/− mice to study medulloblastoma progression, we found that Ptch1 loss of heterozygosity (LOH is an early event that is associated with high levels of cell senescence in preneoplasia. In contrast, advanced tumors have evaded senescence. Remarkably, we discovered that the majority of advanced medulloblastomas display either spontaneous, somatic p53 mutations or Cdkn2a locus inactivation. Consistent with senescence evasion, these p53 mutations are always subsequent to Ptch1 LOH. Introduction of a p53 mutation prevents senescence, accelerates tumor formation, and increases medulloblastoma incidence. Altogether, our results show that evasion of senescence associated with Ptch1 LOH allows progression to advanced tumors.

Progress in computational toxicology.

Science.gov (United States)

Ekins, Sean

2014-01-01

Computational methods have been widely applied to toxicology across pharmaceutical, consumer product and environmental fields over the past decade. Progress in computational toxicology is now reviewed. A literature review was performed on computational models for hepatotoxicity (e.g. for drug-induced liver injury (DILI)), cardiotoxicity, renal toxicity and genotoxicity. In addition various publications have been highlighted that use machine learning methods. Several computational toxicology model datasets from past publications were used to compare Bayesian and Support Vector Machine (SVM) learning methods. The increasing amounts of data for defined toxicology endpoints have enabled machine learning models that have been increasingly used for predictions. It is shown that across many different models Bayesian and SVM perform similarly based on cross validation data. Considerable progress has been made in computational toxicology in a decade in both model development and availability of larger scale or 'big data' models. The future efforts in toxicology data generation will likely provide us with hundreds of thousands of compounds that are readily accessible for machine learning models. These models will cover relevant chemistry space for pharmaceutical, consumer product and environmental applications. Copyright © 2013 Elsevier Inc. All rights reserved.

Slowly progressive fluent aphasia

International Nuclear Information System (INIS)

Sakurai, Yasuhisa; Momose, Toshimitsu; Watanabe, Toshiaki; Ishikawa, Takashi; Iwata, Makoto; Bando, Mitsuaki.

1991-01-01

Three patients with slowly progressive fluent aphasia are reported. One of the patients presented with memory disturbance. They were characterized clinically by having selective deficits in vocabulary, which resulted in impairment of confrontation naming, and auditory comprehension. MRI showed an atrophy not only in the left temporal lobe (including the superior, middle and inferior temporal gyri), hippocampus, parahippocampual gyrus, and fusiform gyrus, but also in the left parietal lobe. I-123 IMP SPECT and F-18 FDG PET were used to determine regional cerebral blood flow and regional cerebral metabolic rate, respectively. In addition to the decreased tracer uptake in the left temporal and/or parietal lobe, a decreased uptake was seen in the bilateral basal ganglia, the inner side of the temporal lobe (including the bilateral hippocampus), the right anterior temporal lobe, and the left thalamus. These findings may deny the previous thought that lesions are localized in slowly progressive fluent aphasia. Furthermore, noticeable difficulty in naming, i.e., patients unable to recognize the right answer, are considered attributable to widespread lesions from the whole left temporal lobe, including the hippocampus, to the right temporal lobe. (N.K.)

Role of Diet and Nutritional Supplements in Parkinson’s Disease Progression

Directory of Open Access Journals (Sweden)

Laurie K. Mischley

2017-01-01

Full Text Available Objectives. The goal of this study is to describe modifiable lifestyle variables associated with reduced rate of Parkinson’s disease (PD progression. Methods. The patient-reported outcomes in PD (PRO-PD were used as the primary outcome measure, and a food frequency questionnaire (FFQ was used to assess dietary intake. In this cross-sectional analysis, regression analysis was performed on baseline data to identify the nutritional and pharmacological interventions associated with the rate of PD progression. All analyses were adjusted for age, gender, and years since diagnosis. Results. 1053 individuals with self-reported idiopathic PD were available for analysis. Foods associated with the reduced rate of PD progression included fresh vegetables, fresh fruit, nuts and seeds, nonfried fish, olive oil, wine, coconut oil, fresh herbs, and spices (P<0.05. Foods associated with more rapid PD progression include canned fruits and vegetables, diet and nondiet soda, fried foods, beef, ice cream, yogurt, and cheese (P<0.05. Nutritional supplements coenzyme Q10 and fish oil were associated with reduced PD progression (P=0.026 and P=0.019, resp., and iron supplementation was associated with faster progression (P=0.022. Discussion. These are the first data to provide evidence that targeted nutrition is associated with the rate of PD progression.

Progressively safer, cheaper demolition of Fernald

International Nuclear Information System (INIS)

Nichols, Robert; Pennington, Norman

2000-01-01

Fluor Fernald, Inc. has been progressively improving Decontamination and Dismantlement (D and D) at the Department of Energy's Fernald Environmental Management Project by applying new technologies and better methodologies to the work. Demolition issues existed in the past that necessitated new or improved solutions to maintain worker safety, protect the environment and accomplish the work in a cost effective manner. Lessons learned from D and D of 80 structures has led to a systematic approach, which can be implemented in various D and D arenas. When facility production was halted, hold-up material and process residues remained in the process piping and components. Over 500,000 pounds of material was removed by workers who completed the tasks two years ahead of schedule, $7 million under budget and with an excellent safety record. This success was the result of detailed planning and irdision of lessons learned as work progressed from facility to facility. Work sequences were developed that reduced airborne contamination. Demolition of structures has been performed at Fernald by carefully selected and qualified subcontractors. Asbestos and lead abatement, equipment, piping and conduit removal, and structural demolition have been completed to progressively higher performance specifications developed by Fluor Fernald based on lessons learned during execution. Safety continues to be the primary consideration in performing potentially hazardous work. Technologies such as hydraulic shears have been developed and used to keep workers away from danger. A new technology, ''Cool Suits,'' has been demonstrated to help prevent heat stress when anti-contamination clothing is required in elevated temperature working conditions. For tall structures, implosion technologies have been employed with progressively improved results, Several other new technologies have been evaluated by Fluor Fernald and applied by subcontractors. The improved technologies included the oxy-gas torch

Predictors of disease progression in HIV infection: a review

Directory of Open Access Journals (Sweden)

Ananworanich Jintanat

2007-05-01

Full Text Available Abstract During the extended clinically latent period associated with Human Immunodeficiency Virus (HIV infection the virus itself is far from latent. This phase of infection generally comes to an end with the development of symptomatic illness. Understanding the factors affecting disease progression can aid treatment commencement and therapeutic monitoring decisions. An example of this is the clear utility of CD4+ T-cell count and HIV-RNA for disease stage and progression assessment. Elements of the immune response such as the diversity of HIV-specific cytotoxic lymphocyte responses and cell-surface CD38 expression correlate significantly with the control of viral replication. However, the relationship between soluble markers of immune activation and disease progression remains inconclusive. In patients on treatment, sustained virological rebound to >10 000 copies/mL is associated with poor clinical outcome. However, the same is not true of transient elevations of HIV RNA (blips. Another virological factor, drug resistance, is becoming a growing problem around the globe and monitoring must play a part in the surveillance and control of the epidemic worldwide. The links between chemokine receptor tropism and rate of disease progression remain uncertain and the clinical utility of monitoring viral strain is yet to be determined. The large number of confounding factors has made investigation of the roles of race and viral subtype difficult, and further research is needed to elucidate their significance. Host factors such as age, HLA and CYP polymorphisms and psychosocial factors remain important, though often unalterable, predictors of disease progression. Although gender and mode of transmission have a lesser role in disease progression, they may impact other markers such as viral load. Finally, readily measurable markers of disease such as total lymphocyte count, haemoglobin, body mass index and delayed type hypersensitivity may come into favour

Changing Assumptions and Progressive Change in Theories of Strategic Organization

DEFF Research Database (Denmark)

Foss, Nicolai J.; Hallberg, Niklas L.

2017-01-01

are often decoupled from the results of empirical testing, changes in assumptions seem closely intertwined with theoretical progress. Using the case of the resource-based view, we suggest that progressive change in theories of strategic organization may come about as a result of scholarly debate and dispute......A commonly held view is that strategic organization theories progress as a result of a Popperian process of bold conjectures and systematic refutations. However, our field also witnesses vibrant debates or disputes about the specific assumptions that our theories rely on, and although these debates...... over what constitutes proper assumptions—even in the absence of corroborating or falsifying empirical evidence. We also discuss how changing assumptions may drive future progress in the resource-based view....

QUIESST: mid-term progress report

NARCIS (Netherlands)

Clairbois, J.-P.; Roo, F. de; Garai, M.; Conter, M.; Defrance, J.; Oltean-Dumbrava, C.; Fusco, I.

2011-01-01

The research QUIESST (QUIetening the Environment of Sustainable Surface Transport) successfully started in November 2009 for 36 months, its objectives and work schedule have already been presented at the INTERNOISE 2010 Congress. This paper will present the progress report at mid-term (18 months):

Progressive macular hypomelanosis: an overview

NARCIS (Netherlands)

Relyveld, Germaine N.; Menke, Henk E.; Westerhof, Wiete

2007-01-01

Progressive macular hypomelanosis (PMH) is a common skin disorder that is often misdiagnosed. Various authors have written about similar skin disorders, referring to them by different names, but we believe that all these similar disorders are part of the same entity.PMH is characterized by

Technological Progress, Exit and Trade

DEFF Research Database (Denmark)

Schröder, Philipp; Sørensen, Allan

productivity exporters are more likely to continue to export, and market exit is typically preceded by periods of contracting market shares. We show that the simple inclusion of exogenous economy wide technological progress into the standard Melitz (2003) model generates a tractable dynamic framework...

Progress at the Shanghai EBIT

International Nuclear Information System (INIS)

He Mianhong; Liu Yong; Yang Yang; Wu Shimin; Chen Weidong; Hu Wei; Guo, Panlin; Lu Di; Fu Yunqing; Huang Min; Zhang Xuemei; Hutton, Roger; Liljeby, Leif; Zou Yaming

2007-01-01

In this report, a brief description of the progress of the Shanghai EBIT project is presented. This is followed by short discussions on the X ray spectra at several electron beam energies and the ion densities in the EBIT at a specific running condition

Spousal Recollections of Early Signs of Primary Progressive Aphasia

Science.gov (United States)

Pozzebon, Margaret; Douglas, Jacinta; Ames, David

2018-01-01

Background: Although primary progressive aphasia (PPA) is characterized by progressive loss of language and communication skills, knowledge about the earliest emerging signs announcing the onset of this condition is limited. Aims: To explore spousal recollections regarding the earliest signs of PPA and to compare the nature of the earliest…

CSF inflammation and axonal damage are increased and correlate in progressive multiple sclerosis

DEFF Research Database (Denmark)

Romme Christensen, Jeppe; Börnsen, Lars; Khademi, Mohsen

2013-01-01

BACKGROUND: The mechanism underlying disease progression in progressive multiple sclerosis (MS) is uncertain. Pathological studies found widespread inflammation in progressive MS brains correlating with disease progression and axonal damage. OBJECTIVES: To study cerebrospinal fluid (CSF) biomarkers...... and clarify whether inflammation and axonal damage are associated in progressive MS. METHODS: Using enzyme-linked immunosorbent assay (ELISA), we analysed CSF from 40 secondary progressive (SPMS), 21 primary progressive (PPMS), and 36 relapsing-remitting (RRMS) and 20 non-inflammatory neurological disease...... (NIND) patients. Twenty-two of the SPMS patients participated in an MBP8298 peptide clinical trial and had CSF follow-up after one year. RESULTS: Compared to NIND patients, inflammatory biomarkers osteopontin and matrix metalloproteinase-9 (MMP9) were increased in all MS patients while CXCL13...

First Nations, Metis and Inuit Education Policy Framework: Progress Report, 2008

Science.gov (United States)

Alberta Education, 2008

2008-01-01

This progress report describes the work currently underway toward improving the success of First Nations, Metis and Inuit (FNMI) students in Alberta. It provides an update on the progress made since the release of the Framework in 2002 and the 2004 Progress Report up to December 31, 2007. Since the release of the Framework, a new Ministry of…

Site-level progression of periodontal disease during a follow-up period

Science.gov (United States)

Morozumi, Toshiya; Nakagawa, Taneaki; Sugaya, Tsutomu; Kawanami, Masamitsu; Suzuki, Fumihiko; Takahashi, Keiso; Abe, Yuzo; Sato, Soh; Makino-Oi, Asako; Saito, Atsushi; Takano, Satomi; Minabe, Masato; Nakayama, Yohei; Ogata, Yorimasa; Kobayashi, Hiroaki; Izumi, Yuichi; Sugano, Naoyuki; Ito, Koichi; Sekino, Satoshi; Numabe, Yukihiro; Fukaya, Chie; Yoshinari, Nobuo; Fukuda, Mitsuo; Noguchi, Toshihide; Kono, Tomoo; Umeda, Makoto; Fujise, Osamu; Nishimura, Fusanori; Yoshimura, Atsutoshi; Hara, Yoshitaka; Nakamura, Toshiaki; Noguchi, Kazuyuki; Kakuta, Erika; Hanada, Nobuhiro; Takashiba, Shogo; Amitani, Yasuharu; Yoshie, Hiromasa

2017-01-01

Periodontal disease is assessed and its progression is determined via observations on a site-by-site basis. Periodontal data are complex and structured in multiple levels; thus, applying a summary statistical approach (i.e., the mean) for site-level evaluations results in loss of information. Previous studies have shown the availability of mixed effects modeling. However, clinically beneficial information on the progression of periodontal disease during the follow-up period is not available. We conducted a multicenter prospective cohort study. Using mixed effects modeling, we analyzed 18,834 sites distributed on 3,139 teeth in 124 patients, and data were collected 5 times over a 24-month follow-up period. The change in the clinical attachment level (CAL) was used as the outcome variable. The CAL at baseline was an important determinant of the CAL changes, which varied widely according to the tooth surface. The salivary levels of periodontal pathogens, such as Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans, were affected by CAL progression. “Linear”- and “burst”-type patterns of CAL progression occurred simultaneously within the same patient. More than half of the teeth that presented burst-type progression sites also presented linear-type progression sites, and most of the progressions were of the linear type. Maxillary premolars and anterior teeth tended to show burst-type progression. The parameters identified in this study may guide practitioners in determining the type and extent of treatment needed at the site and patient levels. In addition, these results show that prior hypotheses concerning "burst" and "linear" theories are not valid. PMID:29206238

Progress in color night vision

NARCIS (Netherlands)

Toet, A.; Hogervorst, M.A.

2012-01-01

We present an overview of our recent progress and the current state-of-the-art techniques of color image fusion for night vision applications. Inspired by previously developed color opponent fusing schemes, we initially developed a simple pixel-based false color-mapping scheme that yielded fused

Progressive Supranuclear Palsy: an Update.

Science.gov (United States)

Armstrong, Melissa J

2018-02-17

Progressive supranuclear palsy (PSP) is a 4R tau neuropathologic entity. While historically defined by the presence of a vertical supranuclear gaze palsy and falls in the first symptomatic year, clinicopathologic studies identify alternate presenting phenotypes. This article reviews the new PSP diagnostic criteria, diagnostic approaches, and treatment strategies. The 2017 International Parkinson and Movement Disorder Society PSP criteria outline 14 core clinical features and 4 clinical clues that combine to diagnose one of eight PSP phenotypes with probable, possible, or suggestive certainty. Evidence supports the use of select imaging approaches in the classic PSP-Richardson syndrome phenotype. Recent trials of putative disease-modifying agents showed no benefit. The new PSP diagnostic criteria incorporating the range of presenting phenotypes have important implications for diagnosis and research. More work is needed to understand how diagnostic evaluations inform phenotype assessment and identify expected progression. Current treatment is symptomatic, but tau-based therapeutics are in active clinical trials.

Local progression and pseudo progression after single fraction or fractionated stereotactic radiotherapy for large brain metastases. A single centre study

Energy Technology Data Exchange (ETDEWEB)

Wiggenraad, R.; Verbeek-de Kanter, A.; Mast, M. [Radiotherapy Centre West, The Hague (Netherlands); Molenaar, R. [Diaconessenhuis, Leiden (Netherlands). Dept. of Neurology; Lycklama a Nijeholt, G. [Medical Centre Haagladen, The Hague (Netherlands). Dept. of Radiology; Vecht, C. [Medical Centre Haagladen, The Hague (Netherlands). Dept. of Neurology; Struikmans, H. [Radiotherapy Centre West, The Hague (Netherlands); Leiden Univ. Medical Centre (Netherlands). Dept. of Radiotherapy; Kal, H.B.

2012-08-15

Purpose: The 1-year local control rates after single-fraction stereotactic radiotherapy (SRT) for brain metastases > 3 cm diameter are less than 70%, but with fractionated SRT (FSRT) higher local control rates have been reported. The purpose of this study was to compare our treatment results with SRT and FSRT for large brain metastases. Materials and methods: In two consecutive periods, 41 patients with 46 brain metastases received SRT with 1 fraction of 15 Gy, while 51 patients with 65 brain metastases received FSRT with 3 fractions of 8 Gy. We included patients with brain metastases with a planning target volume of > 13 cm{sup 3} or metastases in the brainstem. Results: The minimum follow-up of patients still alive was 22 months. Comparing 1 fraction of 15 Gy with 3 fractions of 8 Gy, the 1-year rates of freedom from any local progression (54% and 61%, p = 0.93) and pseudo progression (85% and 75%, p = 0.25) were not significantly different. Overall survival rates were also not different. Conclusion: The 1-year local progression and pseudo progression rates after 1 fraction of 15 Gy or 3 fractions of 8 Gy for large brain metastases and metastases in the brainstem are similar. For better local control rates, FSRT schemes with a higher biological equivalent dose may be necessary. (orig.)

Local progression and pseudo progression after single fraction or fractionated stereotactic radiotherapy for large brain metastases. A single centre study

International Nuclear Information System (INIS)

Wiggenraad, R.; Verbeek-de Kanter, A.; Mast, M.; Molenaar, R.; Lycklama a Nijeholt, G.; Vecht, C.; Struikmans, H.; Leiden Univ. Medical Centre; Kal, H.B.

2012-01-01

Purpose: The 1-year local control rates after single-fraction stereotactic radiotherapy (SRT) for brain metastases > 3 cm diameter are less than 70%, but with fractionated SRT (FSRT) higher local control rates have been reported. The purpose of this study was to compare our treatment results with SRT and FSRT for large brain metastases. Materials and methods: In two consecutive periods, 41 patients with 46 brain metastases received SRT with 1 fraction of 15 Gy, while 51 patients with 65 brain metastases received FSRT with 3 fractions of 8 Gy. We included patients with brain metastases with a planning target volume of > 13 cm 3 or metastases in the brainstem. Results: The minimum follow-up of patients still alive was 22 months. Comparing 1 fraction of 15 Gy with 3 fractions of 8 Gy, the 1-year rates of freedom from any local progression (54% and 61%, p = 0.93) and pseudo progression (85% and 75%, p = 0.25) were not significantly different. Overall survival rates were also not different. Conclusion: The 1-year local progression and pseudo progression rates after 1 fraction of 15 Gy or 3 fractions of 8 Gy for large brain metastases and metastases in the brainstem are similar. For better local control rates, FSRT schemes with a higher biological equivalent dose may be necessary. (orig.)

The Progressive Insurance Automotive X PRIZE Education Program

Energy Technology Data Exchange (ETDEWEB)

Robyn Ready

2011-12-31

The Progressive Insurance Automotive X PRIZE Education Program conducted education and outreach activities and used the competition's technical goals and vehicle demonstrations as a means of attracting students and the public to learn more about advanced vehicle technologies, energy efficiency, climate change, alternative fuels, and the science and math behind efficient vehicle development. The Progressive Insurance Automotive X PRIZE Education Program comprised three integrated components that were designed to educate the general public and create a multi-tiered initiative to engage students and showcase the 21st century skills students will need to compete in our global economy: teamwork, creativity, strong literacy, math and science skills, and innovative thinking. The elements included an Online Experience, a National Student Contest, and in person education events and activites. The project leveraged online connections, strategic partnerships, in-classroom, and beyond-the-classroom initiatives, as well as mainstream media. This education program supported by the U.S. Department of Energy (DOE) also funded the specification of vehicle telemetry and the full development and operation of an interactive online experience that allowed internet users to follow the Progressive Insurance Automotive X PRIZE vehicles as they performed in real-time during the Progressive Insurance Automotive X PRIZE competition events.

Prediction of fibrosis progression in chronic viral hepatitis

Directory of Open Access Journals (Sweden)

Grace Lai-Hung Wong

2014-09-01

Full Text Available Prediction of liver fibrosis progression has a key role in the management of chronic viral hepatitis, as it will be translated into the future risk of cirrhosis and its various complications including hepatocellular carcinoma. Both hepatitis B and C viruses mainly lead to fibrogenesis induced by chronic inflammation and a continuous wound healing response. At the same time direct and indirect profibrogenic responses are also elicited by the viral infection. There are a handful of well-established risk factors for fibrosis progression including older age, male gender, alcohol use, high viral load and co-infection with other viruses. Metabolic syndrome is an evolving risk factor of fibrosis progression. The new notion of regression of advanced fibrosis or even cirrhosis is now strongly supported various clinical studies. Even liver biopsy retains its important role in the assessment of fibrosis progression, various non-invasive assessments have been adopted widely because of their non-invasiveness, which facilitates serial applications in large cohorts of subjects. Transient elastography is one of the most validated tools which has both diagnostic and prognostic role. As there is no single perfect test for liver fibrosis assessment, algorithms combining the most validated noninvasive methods should be considered as initial screening tools.

Preemptive mechanical ventilation can block progressive acute lung injury.

Science.gov (United States)

Sadowitz, Benjamin; Jain, Sumeet; Kollisch-Singule, Michaela; Satalin, Joshua; Andrews, Penny; Habashi, Nader; Gatto, Louis A; Nieman, Gary

2016-02-04

Mortality from acute respiratory distress syndrome (ARDS) remains unacceptable, approaching 45% in certain high-risk patient populations. Treating fulminant ARDS is currently relegated to supportive care measures only. Thus, the best treatment for ARDS may lie with preventing this syndrome from ever occurring. Clinical studies were examined to determine why ARDS has remained resistant to treatment over the past several decades. In addition, both basic science and clinical studies were examined to determine the impact that early, protective mechanical ventilation may have on preventing the development of ARDS in at-risk patients. Fulminant ARDS is highly resistant to both pharmacologic treatment and methods of mechanical ventilation. However, ARDS is a progressive disease with an early treatment window that can be exploited. In particular, protective mechanical ventilation initiated before the onset of lung injury can prevent the progression to ARDS. Airway pressure release ventilation (APRV) is a novel mechanical ventilation strategy for delivering a protective breath that has been shown to block progressive acute lung injury (ALI) and prevent ALI from progressing to ARDS. ARDS mortality currently remains as high as 45% in some studies. As ARDS is a progressive disease, the key to treatment lies with preventing the disease from ever occurring while it remains subclinical. Early protective mechanical ventilation with APRV appears to offer substantial benefit in this regard and may be the prophylactic treatment of choice for preventing ARDS.

Progress risk assessment of oral premalignant lesions with saliva miRNA analysis

International Nuclear Information System (INIS)

Yang, Ya; Li, Yue-xiu; Yang, Xi; Jiang, Long; Zhou, Zuo-jun; Zhu, Ya-qin

2013-01-01

Oral cancer develops through multi-stages: from normal to mild (low grade) dysplasia (LGD), moderate dysplasia, and severe (high grade) dysplasia (HGD), to carcinoma in situ (CIS) and finally invasive oral squamous cell carcinomas (OSCC). Clinical and histological assessments are not reliable in predicting which precursor lesions will progress. The aim of this study was to assess the potential of a noninvasive approach to assess progress risk of oral precancerous lesions. We first used microRNA microarray to profile progressing LGD oral premaligant lesions (OPLs) from non-progressing LGD OPLs in order to explore the possible microRNAs deregulated in low grade OPLs which later progressed to HGD or OSCC. We then used RT-qPCR to detect miRNA targets from the microarray results in saliva samples of these patients. We identified a specific miRNA signature that is aberrantly expressed in progressing oral LGD leukoplakias. Similar expression patterns were detected in saliva samples from these patients. These results show promise for using saliva miRNA signature for monitoring of cancer precursor lesions and early detection of disease progression

Genetics Home Reference: spinal muscular atrophy with progressive myoclonic epilepsy

Science.gov (United States)

... myoclonic epilepsy Spinal muscular atrophy with progressive myoclonic epilepsy Printable PDF Open All Close All Enable Javascript ... boxes. Description Spinal muscular atrophy with progressive myoclonic epilepsy (SMA-PME) is a neurological condition that causes ...

NCI Dictionary | Cancer Trends Progress Report

Science.gov (United States)

The Cancer Trends Progress Report, first issued in 2001, summarizes our nation's advances against cancer in relation to Healthy People targets set forth by the Department of Health and Human Services.

Custom Report | Cancer Trends Progress Report

Science.gov (United States)

The Cancer Trends Progress Report, first issued in 2001, summarizes our nation's advances against cancer in relation to Healthy People targets set forth by the Department of Health and Human Services.

Fat Consumption | Cancer Trends Progress Report

Science.gov (United States)

The Cancer Trends Progress Report, first issued in 2001, summarizes our nation's advances against cancer in relation to Healthy People targets set forth by the Department of Health and Human Services.

Alcohol Consumption | Cancer Trends Progress Report

Science.gov (United States)

The Cancer Trends Progress Report, first issued in 2001, summarizes our nation's advances against cancer in relation to Healthy People targets set forth by the Department of Health and Human Services.

The Effect of Weekly Progress Reports on Academic Achievement.

Science.gov (United States)

Armour, Katherine S.

This study investigated the effect of weekly progress reports on the academic achievement of seventh grade language arts students. It also investigated the effects of weekly progress reports on locus of control attribution and the relationship between academic achievement and locus of control attribution. The study took place in a suburban school…

Progress toward Topology Optimization (TO) for Additive Manufacturing (AM) and Fatigue

Science.gov (United States)

2017-06-15

ARL-CR-0815 ● JUNE 2017 US Army Research Laboratory Progress toward Topology Optimization (TO) for Additive Manufacturing (AM...needed. Do not return it to the originator. ARL-CR-0815 ● JUNE 2017 US Army Research Laboratory Progress toward Topology ...Report 3. DATES COVERED (From - To) May 2015–May 2017 4. TITLE AND SUBTITLE Progress toward Topology Optimization (TO) for Additive Manufacturing

Biophysical insight into the anti-amyloidogenic behavior of taurine.

Science.gov (United States)

Chaturvedi, Sumit Kumar; Alam, Parvez; Khan, Javed Masood; Siddiqui, Mohd Khursheed; Kalaiarasan, Ponnusamy; Subbarao, Naidu; Ahmad, Zeeshan; Khan, Rizwan Hasan

2015-09-01

In this work, we investigated the inhibitory ability of taurine on the aggregation of Human serum albumin (HSA) and also examined how it controls the kinetic parameters of the aggregation process. We demonstrated the structural alterations in the HSA after binding to the taurine at 65 °C by exploiting various biophysical techniques. UV-vis spectroscopy was used to check the turbidometric changes in the protein. Thioflavin T fluorescence kinetics was subjected to explore kinetic parameters comparing the amyloid formation in the presence of varying concentration of taurine. Further, Congo red binding and ANS binding assays were performed to determine the inhibitory effect of taurine on HSA fibrillation process and surface hydrophobicity modifications occurring before and after the addition of taurine with protein, respectively. Far UV CD and Dynamic Light Scattering (DLS) confirmed that taurine stabilized the protein α-helical structure and formed complex with HSA which is further supported by differential scanning calorimetry (DSC). Moreover, microscopic imaging techniques were also done to analyze the morphology of aggregation formed. Taurine is also capable of altering the cytotoxicity of the proteinaceous aggregates. Molecular docking study also deciphered the possible residues involved in protein and drug interaction. Copyright © 2015 Elsevier B.V. All rights reserved.

Prelysosomal Compartments in the Unconventional Secretion of Amyloidogenic Seeds

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Helena Borland

2017-01-01

Full Text Available A mechanistic link between neuron-to-neuron transmission of secreted amyloid and propagation of protein malconformation cytopathology and disease has recently been uncovered in animal models. An enormous interest in the unconventional secretion of amyloids from neurons has followed. Amphisomes and late endosomes are the penultimate maturation products of the autophagosomal and endosomal pathways, respectively, and normally fuse with lysosomes for degradation. However, under conditions of perturbed membrane trafficking and/or lysosomal deficiency, prelysosomal compartments may instead fuse with the plasma membrane to release any contained amyloid. After a brief introduction to the endosomal and autophagosomal pathways, we discuss the evidence for autophagosomal secretion (exophagy of amyloids, with a comparative emphasis on Aβ1–42 and α-synuclein, as luminal and cytosolic amyloids, respectively. The ESCRT-mediated import of cytosolic amyloid into late endosomal exosomes, a known vehicle of transmission of macromolecules between cells, is also reviewed. Finally, mechanisms of lysosomal dysfunction, deficiency, and exocytosis are exemplified in the context of genetically identified risk factors, mainly for Parkinson’s disease. Exocytosis of prelysosomal or lysosomal organelles is a last resort for clearance of cytotoxic material and alleviates cytopathy. However, they also represent a vehicle for the concentration, posttranslational modification, and secretion of amyloid seeds.

Prelysosomal Compartments in the Unconventional Secretion of Amyloidogenic Seeds

DEFF Research Database (Denmark)

Borland, Helena; Vilhardt, Frederik

2017-01-01

. The ESCRT-mediated import of cytosolic amyloid into late endosomal exosomes, a known vehicle of transmission of macromolecules between cells, is also reviewed. Finally, mechanisms of lysosomal dysfunction, deficiency, and exocytosis are exemplified in the context of genetically identified risk factors......, mainly for Parkinson's disease. Exocytosis of prelysosomal or lysosomal organelles is a last resort for clearance of cytotoxic material and alleviates cytopathy. However, they also represent a vehicle for the concentration, posttranslational modification, and secretion of amyloid seeds....

SIRT6 knockout cells resist apoptosis initiation but not progression: a computational method to evaluate the progression of apoptosis.

Science.gov (United States)

Domanskyi, Sergii; Nicholatos, Justin W; Schilling, Joshua E; Privman, Vladimir; Libert, Sergiy

2017-11-01

Apoptosis is essential for numerous processes, such as development, resistance to infections, and suppression of tumorigenesis. Here, we investigate the influence of the nutrient sensing and longevity-assuring enzyme SIRT6 on the dynamics of apoptosis triggered by serum starvation. Specifically, we characterize the progression of apoptosis in wild type and SIRT6 deficient mouse embryonic fibroblasts using time-lapse flow cytometry and computational modelling based on rate-equations and cell distribution analysis. We find that SIRT6 deficient cells resist apoptosis by delaying its initiation. Interestingly, once apoptosis is initiated, the rate of its progression is higher in SIRT6 null cells compared to identically cultured wild type cells. However, SIRT6 null cells succumb to apoptosis more slowly, not only in response to nutrient deprivation but also in response to other stresses. Our data suggest that SIRT6 plays a role in several distinct steps of apoptosis. Overall, we demonstrate the utility of our computational model to describe stages of apoptosis progression and the integrity of the cellular membrane. Such measurements will be useful in a broad range of biological applications.

Progress Report Oct to Dec 1975(2)

International Nuclear Information System (INIS)

1976-01-01

Progress report NO. 2 of Tehran Nuclear Research Centre outlines a brief description of the progress made in each section of the centre. A complete list of dissertations for Master's degrees studied at the Nuclear Research Centre and a list of new technical employee are given at the beginning of the report. Research activities in the third section include, isotope separation, laser research, radiation chemistry, reactor management, environmental research, neutron physics, reactor engineering, and nuclear medicine. The fourth section deals with education and training; technical support and health physics are discussed in sections five and six respectively

Communication of nuclear data progress (No.29)

International Nuclear Information System (INIS)

2003-01-01

This is the 29th issue of Communication of Nuclear Data Progress (CNDP), in which the progress and achievements in nuclear data field in 2002 in China are carried. It includes the evaluations of complete neutron data for n+ 55,58 Mn, 99,100 Mo and covariance data evaluation for 63,65,Nat Cu; the evaluations of mass distribution data from 252 Cf spontaneous fission, prompt and delayed neutron yields for 233 U; the studies for level width broaden effect; benchmark testing calculation for 232 Th; establishment of file-6 of n+ 12 C for CENDL-3 et al. (authors)

Research progress of functional MRI in depression

International Nuclear Information System (INIS)

Xie Shenghui; Niu Guangming; Han Xiaodong; Qiao Pengfei

2013-01-01

The mood disorders of depression are associated with abnormalities of brain structure and function, and exploring their pathological mechanism has important significance for the choice of treatment and the curative effect evaluation. In recent years, the research of MRI on brain structure and function of depression has made great progress, especially in functional magnetic resonance imaging (fMRI). fMRI can detect the functional change in real time, and also can display the activity of brain and changes in the nerve pathways in patients with depression. This article summarizes the present research situation and progress of MRI in the diagnosis of depression. (authors)

Sulfur dioxide allowances. Trading and technological progress

International Nuclear Information System (INIS)

Kumar, Surender; Managi, Shunsuke

2010-01-01

The US Clean Air Act Amendments introduce an emissions trading system to regulate SO 2 emissions. This study finds that changes in SO 2 emissions prices are related to innovations induced by these amendments. We find that electricity-generating plants are able to increase electricity output and reduce emissions of SO 2 and NO x from 1995 to 2007 due to the introduction of the allowance trading system. However, compared to the approximate 8% per year of exogenous technological progress, the induced effect is relatively small, and the contribution of the induced effect to overall technological progress is about 1-2%. (author)

Progressive dysphagia in limb-girdle muscular dystrophy type 2B.

LENUS (Irish Health Repository)

Walsh, Richard

2012-02-01

Dysphagia has not been reported in genetically confirmed limb-girdle muscular dystrophy type 2B (LGMD2B). A 40-year-old woman reported exercise-induced calf pain at age 34, followed by progressive lower and upper limb weakness. At age 38, progressive dysphagia for solids, and subsequently liquids, ensued. Endoscopic and videofluoroscopic-radiological findings indicated a myopathic swallowing disorder. Molecular genetic analysis confirmed two dysferlin gene mutations consistent with a compound heterozygote state. Progressive dysphagia should be considered as part of the expanding dysferlinopathy phenotype.

CKD Progression and Mortality among Hispanics and Non-Hispanics.

Science.gov (United States)

Fischer, Michael J; Hsu, Jesse Y; Lora, Claudia M; Ricardo, Ana C; Anderson, Amanda H; Bazzano, Lydia; Cuevas, Magdalena M; Hsu, Chi-Yuan; Kusek, John W; Renteria, Amada; Ojo, Akinlolu O; Raj, Dominic S; Rosas, Sylvia E; Pan, Qiang; Yaffe, Kristine; Go, Alan S; Lash, James P

2016-11-01

Although recommended approaches to CKD management are achieved less often in Hispanics than in non-Hispanics, whether long-term outcomes differ between these groups is unclear. In a prospective longitudinal analysis of participants enrolled into the Chronic Renal Insufficiency Cohort (CRIC) and Hispanic-CRIC Studies, we used Cox proportional hazards models to determine the association between race/ethnicity, CKD progression (50% eGFR loss or incident ESRD), incident ESRD, and all-cause mortality, and linear mixed-effects models to assess differences in eGFR slope. Among 3785 participants, 13% were Hispanic, 43% were non-Hispanic white (NHW), and 44% were non-Hispanic black (NHB). Over a median follow-up of 5.1 years for Hispanics and 6.8 years for non-Hispanics, 27.6% of all participants had CKD progression, 21.3% reached incident ESRD, and 18.3% died. Hispanics had significantly higher rates of CKD progression, incident ESRD, and mean annual decline in eGFR than did NHW (P<0.05) but not NHB. Hispanics had a mortality rate similar to that of NHW but lower than that of NHB (P<0.05). In adjusted analyses, the risk of CKD progression did not differ between Hispanics and NHW or NHB. However, among nondiabetic participants, compared with NHB, Hispanics had a lower risk of CKD progression (hazard ratio, 0.61; 95% confidence interval, 0.39 to 0.95) and incident ESRD (hazard ratio, 0.50; 95% confidence interval, 0.30 to 0.84). At higher levels of urine protein, Hispanics had a significantly lower risk of mortality than did non-Hispanics (P<0.05). Thus, important differences in CKD progression and mortality exist between Hispanics and non-Hispanics and may be affected by proteinuria and diabetes. Copyright © 2016 by the American Society of Nephrology.

Design and development of progressive tool for manufacturing washer

Science.gov (United States)

Annigeri, Ulhas K.; Raghavendra Ravi Kiran, K.; Deepthi, Y. P.

2017-07-01

In a progressive tool the raw material is worked at different station to finally fabricate the component. A progressive tool is a lucrative tool for mass production of components. A lot of automobile and other transport industries develop progressive tool for the production of components. The design of tool involves lot of planning and the same amount of skill of process planning is required in the fabrication of the tool. The design also involves use of thumb rules and standard elements as per experience gained in practice. Manufacturing the press tool is a laborious task as special jigs and fixtures have to be designed for the purpose. Assembly of all the press tool elements is another task where use of accurate measuring instruments for alignment of various tool elements is important. In the present study, design and fabrication of progressive press tool for production of washer has been developed and the press tool has been tried out on a mechanical type of press. The components produced are to dimensions.

what drives progressive motor deifcits in patients with acute pontine infarction?

Institute of Scientific and Technical Information of China (English)

Jue-bao Li; Rui-dong Cheng; Liang Zhou; Wan-shun Wen; Gen-ying Zhu; Liang Tian; Xiang-ming Ye

2015-01-01

Progressive motor deficits are relatively common in acute pontine infarction and frequently associated with increased functional disability. However, the factors that affect the progression of clinical motor weakness are largely unknown. Previous studies have suggested that pontine infarctions are caused mainly by basilar artery stenosis and penetrating artery disease. Recently, lower pons lesions in patients with acute pontine infarctions have been reported to be related to progressive motor deifcits, and ensuing that damage to the corticospinal tracts may be respon-sible for the worsening of neurological symptoms. Here, we review studies on motor weakness progression in pontine infarction and discuss the mechanisms that may underlie the neurologic worsening.

What drives progressive motor deficits in patients with acute pontine infarction?

Directory of Open Access Journals (Sweden)

Jue-bao Li

2015-01-01

Full Text Available Progressive motor deficits are relatively common in acute pontine infarction and frequently associated with increased functional disability. However, the factors that affect the progression of clinical motor weakness are largely unknown. Previous studies have suggested that pontine infarctions are caused mainly by basilar artery stenosis and penetrating artery disease. Recently, lower pons lesions in patients with acute pontine infarctions have been reported to be related to progressive motor deficits, and ensuing that damage to the corticospinal tracts may be responsible for the worsening of neurological symptoms. Here, we review studies on motor weakness progression in pontine infarction and discuss the mechanisms that may underlie the neurologic worsening.

From Domination to Autonomy: Two Eras of Progress in World-sociological Perspective

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Peter Wagner

2015-12-01

Full Text Available In recent decades, the belief in progress that was widespread across the two centuries following the French Revolution has withered away. This article suggests, though, that the diagnosis of the end of progress can be used as an occasion to rethink what progress meant and what it might mean today. The proposal for rethinking proceeds in two big steps. First, the meaning of progress that was inherited from the Enlightenment is reconstructed and contrasted with the way progress actually occurred in history. In this step, it is demonstrated that progress was expected through human autonomy, but that it was actually brought about by domination and resistance to domination. A look at the short revival of progress after the middle of the twentieth century will confirm this insight and direct the attention to the transformation of the world over the past half century, on which the second step focuses. This socio-political transformation is analyzed as spelling (almost the end of formal domination. The current era has often been characterized by the tendencies towards globalization and individualization as well as, normatively, by the increasingly hegemonic commitment to human rights and democracy. A critical analysis of the current socio-political constellation, however, shows that the end of formal domination does not mean the end of history; it rather requires the elaboration of a new understanding of possible progress. Progress can no longer predominantly be achieved through resistance to domination, but rather through autonomous collective action and through the critical interpretation of the world one finds onself in.

Case management considerations of progressive dementia in a home setting.

Science.gov (United States)

Pierce, Mary Ellen

2010-01-01

Nursing theory, research, and best practice guidelines contribute substantially to the field of dementia care. Interventional plans are challenged most by those dementias considered progressive and deteriorative in nature, requiring ongoing reassessment and modification of care practices as the clinical course changes. The purpose of this article is to provide guidelines for case managers in the development of effective, individualized care plans for clients with progressive dementia residing in a home setting. The application of these guidelines is illustrated through the presentation of an actual case. The practice setting is a private home in the Pacific Northwest. Geriatric case management is provided by an RN case manager. Progressive dementia presents challenges to home care. Professional case management using comprehensive, holistic assessment, collaborative approaches, and best practice fundamentals serve to create an effective, individualized plan of care. The increasing geriatric population presents great opportunities for case managers in strategic management for creating successful home care models in clients with progressive dementia. Use of nursing diagnoses, dementia research, and collaborative approaches with families and other medical providers creates a viable alternative for clients with progressive dementia.

Progress in semiconductor drift detectors

International Nuclear Information System (INIS)

Rehak, P.; Walton, J.; Gatti, E.

1985-01-01

Progress in testing semiconductor drift detectors is reported. Generally better position and energy resolutions were obtained than resolutions published previously. The improvement is mostly due to new electronics better matched to different detectors. It is shown that semiconductor drift detectors are becoming versatile and reliable detectors for position and energy measurements

Minority Student Progress Report, 1991.

Science.gov (United States)

Diaz, Porfirio R.; Luan, Jing

This report offers a consolidated systemwide analysis of key issues and recommendations for improvement of minority recruitment and retention at Arizona State Universities and an evaluation of progress toward achieving Arizona Board of Regents (ABOR) approved recruitment and graduation goals. A description of ABOR system goals notes three goals:…

Monitoring Students' Academic & Disciplinary Progression.

Science.gov (United States)

McDonald, Fred; Kellogg, Larry J.

This document outlines the objectives and procedures of a program at a New Mexico school district whose purpose is to enable school personnel to systematically monitor students' academic and disciplinary progression. The objectives of the program are to diagnose academic or disciplinary problems and prescribe remedies, to establish an oncampus…

White matter disease correlates with lexical retrieval deficits in primary progressive aphasia

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John P. Powers

2013-12-01

Full Text Available Objective: To relate fractional anisotropy changes associated with the semantic and logopenic variants of primary progressive aphasia to measures of lexical retrieval.Methods: We collected neuropsychological testing, volumetric MRI, and diffusion-weighted imaging on semantic variant primary progressive aphasia (n=11 and logopenic variant primary progressive aphasia (n=13 patients diagnosed using published criteria. We also acquired neuroimaging data on a group of demographically comparable healthy seniors (n=34. Fractional anisotropy was calculated and analyzed using a white matter tract-specific analysis approach. This approach utilizes anatomically guided data reduction to increase sensitivity and localizes results within canonically defined tracts. We used non-parametric, cluster-based statistical analysis to relate language performance to fractional anisotropy and determine regions of reduced fractional anisotropy in patients. Results: We found widespread fractional anisotropy reductions in white matter for both variants of primary progressive aphasia. Fractional anisotropy was related to both confrontation naming and category naming fluency performance in left uncinate fasciculus and corpus callosum in semantic variant primary progressive aphasia and left superior and inferior longitudinal fasciculi in logopenic variant primary progressive aphasia. Conclusions: Semantic variant primary progressive aphasia and logopenic variant primary progressive aphasia are associated with distinct disruptions of a large-scale network implicated in lexical retrieval, and the white matter disease in each phenotype may contribute to language impairments including lexical retrieval.

All delays before radiotherapy risk progression of Merkel cell carcinoma

International Nuclear Information System (INIS)

Tsang, G.; O'Brien, P.; Robertson, R.; Hamilton, C.; Wratten, C.; Denham, J.

2004-01-01

Prolonged waiting times for radiotherapy have resulted in many centres assigning priorities to various patient or diagnostic groups. A high risk of progression on a waiting list is one factor that would reasonably influence the priority. The present descriptive study of 27 patients with Merkel cell carcinoma (MCC) found that a median wait of 24 days for radiotherapy is associated with a high risk of progression. Eleven (41%) of 27 patients developed progressive disease, including five (45%) of 11 patients waiting for adjuvant radiotherapy. Patients treated adjuvantly also had longer waiting times prior to their initial radiotherapy consultation (median 41 days), which may have contributed to the rate of progression. Merkel cell carcinoma is an aggressive but curable malignancy and appropriate management should include efforts to minimize all potential delays prior to the commencement of radiotherapy. Copyright (2004) Blackwell Science Pty Ltd

Effect of Single-Sex Education on Progress in GCSE

Science.gov (United States)

Malacova, Eva

2007-01-01

Multilevel modeling was carried out on national value-added data to study the effects of single-sex education on the progress of pupils from 2002 Key Stage 3 to 2004 GCSE. The analysis suggests that pupils in a selective environment achieve higher progress in single-sex schools; however, the advantage of single-sex schooling seems to decrease with…

CERN concludes year of strong progress towards the LHC

CERN Multimedia

2006-01-01

Speaking at the 135th session of the CERN Council, the Director General, Robert Aymar, hailed a year of impressive progress towards the LHC project. 'In one year, we have made great progress,' he said. 'The challenge is not over, of course, but we have great confidence of maintaining the schedule for start-up in 2007.'

Genetics Home Reference: progressive supranuclear palsy

Science.gov (United States)

... slow and slurred speech (dysarthria) and trouble swallowing (dysphagia). Most affected individuals also experience changes in personality ... UK): Treatment of Progressive Supranuclear Palsy Partners in Parkinson's: Movement Disorder Specialist Finder University of California, San ...

Genetics Home Reference: progressive external ophthalmoplegia

Science.gov (United States)

... and can affect both males and females, but fathers do not pass traits associated with changes in ... Genetic Testing (4 links) Genetic Testing Registry: Autosomal dominant progressive external ophthalmoplegia with mitochondrial DNA deletions 1 ...

Imagine stopping the progression of Alzheimer's

Science.gov (United States)

... Issue Past Issues Imagine stopping the progression of Alzheimer's Past Issues / Fall 2006 Table of Contents For ... I have friends and loved ones suffering from Alzheimer's. But I can imagine… and hope for… a ...

Liquefaction of Semen Generates and Later Degrades a Conserved Semenogelin Peptide That Enhances HIV Infection

Science.gov (United States)

Liu, Haichuan; Usmani, Shariq M.; Neidleman, Jason; Müller, Janis A.; Avila-Herrera, Aram; Gawanbacht, Ali; Zirafi, Onofrio; Chu, Simon; Dong, Ming; Kumar, Senthil T.; Smith, James F.; Pollard, Katherine S.; Fändrich, Marcus; Kirchhoff, Frank; Münch, Jan; Witkowska, H. Ewa; Greene, Warner C.

2014-01-01

ABSTRACT Semen enhances HIV infection in vitro, but how long it retains this activity has not been carefully examined. Immediately postejaculation, semen exists as a semisolid coagulum, which then converts to a more liquid form in a process termed liquefaction. We demonstrate that early during liquefaction, semen exhibits maximal HIV-enhancing activity that gradually declines upon further incubation. The decline in HIV-enhancing activity parallels the degradation of peptide fragments derived from the semenogelins (SEMs), the major components of the coagulum that are cleaved in a site-specific and progressive manner upon initiation of liquefaction. Because amyloid fibrils generated from SEM fragments were recently demonstrated to enhance HIV infection, we set out to determine whether any of the liquefaction-generated SEM fragments associate with the presence of HIV-enhancing activity. We identify SEM1 from amino acids 86 to 107 [SEM1(86-107)] to be a short, cationic, amyloidogenic SEM peptide that is generated early in the process of liquefaction but that, conversely, is lost during prolonged liquefaction due to the activity of serine proteases. Synthetic SEM1(86-107) amyloids directly bind HIV-1 virions and are sufficient to enhance HIV infection of permissive cells. Furthermore, endogenous seminal levels of SEM1(86-107) correlate with donor-dependent variations in viral enhancement activity, and antibodies generated against SEM1(86-107) recognize endogenous amyloids in human semen. The amyloidogenic potential of SEM1(86-107) and its virus-enhancing properties are conserved among great apes, suggesting an evolutionarily conserved function. These studies identify SEM1(86-107) to be a key, HIV-enhancing amyloid species in human semen and underscore the dynamic nature of semen's HIV-enhancing activity. IMPORTANCE Semen, the most common vehicle for HIV transmission, enhances HIV infection in vitro, but how long it retains this activity has not been investigated. Semen

Progress in optics

CERN Document Server

Wolf, Emil

1977-01-01

In the thirty-seven years that have gone by since the first volume of Progress in Optics was published, optics has become one of the most dynamic fields of science. At the time of inception of this series, the first lasers were only just becoming operational, holography was in its infancy, subjects such as fiber optics, integrated optics and optoelectronics did not exist and quantum optics was the domain of only a few physicists. The term photonics had not yet been coined. Today these fields are flourishing and have become areas of specialisation for many science and engineering students and n

HSX progress report

International Nuclear Information System (INIS)

1994-01-01

Brief statements on the progress of the design and construction of the HSX experiment are reported. Topics covered include the modular and auxiliary coil systems, the coil support structure, vacuum vessel, the ECH system, the magnet power supply and site. The proposed budget for Year 2 (August 1, 1994 through July 31, 1995) is presented. The effects of a flat funding profile (based on Year 2 budget level of $1137K) on out-years and the HSX project schedule are discussed. The stretching out of the program to accommodate the reduced funding profile should result in only a slight delay in HSX operations

Progress in optics

CERN Document Server

Wolf, Emil

2006-01-01

In the thirty-seven years that have gone by since the first volume of Progress in Optics was published, optics has become one of the most dynamic fields of science. At the time of inception of this series, the first lasers were only just becoming operational, holography was in its infancy, subjects such as fiber optics, integrated optics and optoelectronics did not exist and quantum optics was the domain of only a few physicists. The term photonics had not yet been coined. Today these fields are flourishing and have become areas of specialisation for many science and engineering students and n

Mathieu Progressive Waves

Science.gov (United States)

Andrei, B. Utkin

2011-10-01

A new family of exact solutions to the wave equation representing relatively undistorted progressive waves is constructed using separation of variables in the elliptic cylindrical coordinates and one of the Bateman transforms. The general form of this Bateman transform in an orthogonal curvilinear cylindrical coordinate system is discussed and a specific problem of physical feasibility of the obtained solutions, connected with their dependence on the cyclic coordinate, is addressed. The limiting case of zero eccentricity, in which the elliptic cylindrical coordinates turn into their circular cylindrical counterparts, is shown to correspond to the focused wave modes of the Bessel-Gauss type.

The magnesium chelation step in chlorophyll biosynthesis. Progress report 1993

Energy Technology Data Exchange (ETDEWEB)

Weinstein, J.D.

1993-12-31

Progress is reported on the identification and fractionation of Magnesium chealatase, an enzyme involved in addition of Mg to chlorophyll during the later`s biosynthesis. Progress is documented as a series of synopsis of published and unpublished papers by the author.

Plasma lipid peroxidation and progression of disability in multiple sclerosis

NARCIS (Netherlands)

Koch, M.; Mostert, J.; Arutjunyan, A. V.; Stepanov, M.; Teelken, A.; Heersema, D.; De Keyser, J.

Oxidative stress has been implicated in the pathophysiology of multiple sclerosis (MS), but its relation to disease progression is uncertain. To evaluate the relationship of plasma lipid peroxidation with progression of disability in MS, we measured blood plasma fluorescent lipid peroxidation