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Sample records for spontaneous macromolecular damage

  1. Radiation damage to nucleoprotein complexes in macromolecular crystallography

    International Nuclear Information System (INIS)

    Bury, Charles; Garman, Elspeth F.; Ginn, Helen Mary; Ravelli, Raimond B. G.; Carmichael, Ian; Kneale, Geoff; McGeehan, John E.

    2015-01-01

    Quantitative X-ray induced radiation damage studies employing a model protein–DNA complex revealed a striking partition of damage sites. The DNA component was observed to be far more resistant to specific damage compared with the protein. Significant progress has been made in macromolecular crystallography over recent years in both the understanding and mitigation of X-ray induced radiation damage when collecting diffraction data from crystalline proteins. In contrast, despite the large field that is productively engaged in the study of radiation chemistry of nucleic acids, particularly of DNA, there are currently very few X-ray crystallographic studies on radiation damage mechanisms in nucleic acids. Quantitative comparison of damage to protein and DNA crystals separately is challenging, but many of the issues are circumvented by studying pre-formed biological nucleoprotein complexes where direct comparison of each component can be made under the same controlled conditions. Here a model protein–DNA complex C.Esp1396I is employed to investigate specific damage mechanisms for protein and DNA in a biologically relevant complex over a large dose range (2.07–44.63 MGy). In order to allow a quantitative analysis of radiation damage sites from a complex series of macromolecular diffraction data, a computational method has been developed that is generally applicable to the field. Typical specific damage was observed for both the protein on particular amino acids and for the DNA on, for example, the cleavage of base-sugar N 1 —C and sugar-phosphate C—O bonds. Strikingly the DNA component was determined to be far more resistant to specific damage than the protein for the investigated dose range. At low doses the protein was observed to be susceptible to radiation damage while the DNA was far more resistant, damage only being observed at significantly higher doses

  2. Experimental procedure for the characterization of radiation damage in macromolecular crystals

    International Nuclear Information System (INIS)

    Leal, Ricardo M. F.; Bourenkov, Gleb P.; Svensson, Olof; Spruce, Darren; Guijarro, Matias; Popov, Alexander N.

    2011-01-01

    A novel automatic procedure to determine the sensitivity of macromolecular crystals to radiation damage is presented. The information extracted from this procedure can be directly used for optimal planning of data collection or/and beamline calibration. A reliable and reproducible method to automatically characterize the radiation sensitivity of macromolecular crystals at the ESRF beamlines has been developed. This new approach uses the slope of the linear dependence of the overall isotropic B-factor with absorbed dose as the damage metric. The method has been implemented through an automated procedure using the EDNA on-line data analysis framework and the MxCuBE data collection control interface. The outcome of the procedure can be directly used to design an optimal data collection strategy. The results of tests carried out on a number of model and real-life crystal systems are presented

  3. Spontaneous perseverative turning in rats with radiation-induced hippocampal damage

    International Nuclear Information System (INIS)

    Mickley, G.A.; Ferguson, J.L.; Nemeth, T.J.; Mulvihill, M.A.; Alderks, C.E.

    1989-01-01

    This study found a new behavioral correlate of lesions specific to the dentate granule cell layer of the hippocampus: spontaneous perseverative turning. Irradiation of a portion of the neonatal rat cerebral hemispheres produced hypoplasia of the granule cell layer of the hippocampal dentate gyrus while sparing the rest of the brain. Radiation-induced damage to the hippocampal formation caused rats placed in bowls to spontaneously turn in long, slow bouts without reversals. Irradiated subjects also exhibited other behaviors characteristic of hippocampal damage (e.g., perseveration in spontaneous exploration of the arms of a T-maze, retarded acquisition of a passive avoidance task, and increased horizontal locomotion). These data extend previously reported behavioral correlates of fascia dentata lesions and suggest the usefulness of a bout analysis of spontaneous bowl turning as a measure of nondiscrete-trial spontaneous alternation and a sensitive additional indicator of radiation-induced hippocampal damage

  4. Indicators of Macromolecular Oxidative Damage and Antioxidant Defence Examinees Exposed to the Radar Frequencies 1.5 - 10.9 GHz

    International Nuclear Information System (INIS)

    Marjanovic, A.M.; Flajs, D.; Pavicic, I.; Domijan, A.

    2011-01-01

    Radar is an object-detection system which uses microwaves (Mw). As a result of increased use of radar there is a rising concern regarding health effects of Mw radiation on human body. Living organisms are complex electrochemical systems being evolved in a relatively narrow range of well-defined environmental parameters. For life to be maintained these parameters must be kept within their normal range, since deviations can induce biochemical effects causing cell function impairment and disease. Some theories indicate connection between Mw radiation, oxidative damage as well as antioxidant defence of organism. Aim of this study was to evaluate level and damage of macromolecular structures - proteins and lipids in blood of men occupationally exposed to Mw radiation. Concentration of glutathione (GSH), a known indicator of organism antioxidant defence, was also determined. Blood samples were collected from 27 male workers occupationally exposed to radar frequencies 1.5 to 10.9 GHz. Corresponding control group (N = 8) was a part of study. Concentrations of total and oxidised proteins, protein carbonyls, and GSH were measured by spectrophotometric method, while malondialdeyde (MDA), product of lipid peroxidation, was determined by high performance liquid chromatography (HPLC). Gained concentrations of oxidised proteins, GSH and MDA were presented in relation to total proteins. Concentration of oxidised proteins between control and exposed group of examinees did not show any significant statistical difference. However, concentration of GSH in exposed group was found considerably decreased, while concentration of MDA was found to be increased. Results indicate that Mw radiation of radar operating at frequencies 1.5 - 10.9 GHz could cause damage to proteins and lipids in addition to impairment of antioxidant defence of organism. (author)

  5. Impaired spontaneous belief inference following acquired damage to the left posterior temporoparietal junction.

    Science.gov (United States)

    Biervoye, Aurélie; Dricot, Laurence; Ivanoiu, Adrian; Samson, Dana

    2016-10-01

    Efficient social interactions require taking into account other people's mental states such as their beliefs, intentions or emotions. Recent studies have shown that in some social situations at least, we do spontaneously take into account others' mental states. The extent to which we have dedicated brain areas for such spontaneous perspective taking is however still unclear. Here, we report two brain-damaged patients whose common lesions were almost exclusively in the left posterior temporoparietal junction (TPJp) and who both showed the same striking and distinctive theory of mind (ToM) deficit. More specifically, they had an inability to take into account someone else's belief unless they were explicitly instructed to tell what that other person thinks or what that person will do. These patients offer a unique insight into the causal link between a specific subregion of the TPJ and a specific cognitive facet of ToM. © The Author (2016). Published by Oxford University Press.

  6. EXERCISE TRAINING IMPROVES CARDIOVASCULAR AUTONOMIC ACTIVITY AND ATTENUATES RENAL DAMAGE IN SPONTANEOUSLY HYPERTENSIVE RATS

    Directory of Open Access Journals (Sweden)

    Octávio Barbosa Neto

    2013-03-01

    Full Text Available Experiments were performed to determine the influence of exercise training by swimming on cardiovascular autonomic control and renal morphology in spontaneously hypertensive rats (SHR and Wystar-Kyoto (WKY rats. Sedentary normotensive (SN, trained normotensive (TN, sedentary hypertensive (SH, and trained hypertensive (TH rats were included in this study. Arterial pressure (AP, heart rate (HR, means of power spectral analysis of HR (HRV and systolic AP variability (SAPV were recorded in baseline conditions. Following, the HR baroreflex and autonomic tonus control were assessed. At the end, all animals were euthanized and their kidneys were excised to evaluate renal damage. Resting bradycardia was observed in TH and TN rats compared with their respective sedentary animals (p < 0.05. Exercise training attenuated AP in TH vs. SH (p < 0.001. The LF component of HRV and SAPV were lower in TH than SH (p < 0.05. The LF/HF relation was lower in TH than SH and SN (p < 0.05. TN and TH rats showed a sympathetic tonus reduction in comparison to SN and SH rats (p < 0.001. The TH presented an increased vagal tonus compared to SH (p < 0.05. Exercise training improved baroreflex control of HR in TH group versus SH (p < 0.05. The TH showed a lower number of sclerotic glomeruli compared to SH (p < 0.005. The exercise training decrease the glomerular indexes in TN and TH (p < 0.05. Further analysis showed a significant correlation between sympathetic nervous activity and AP levels (p < 0.05. A positive association was also found between sympathetic nervous activity and glomerular index (p < 0.05. Therefore, the exercise training reduces AP and attenuates renal damage. In addition, the attenuation of renal injury was associated with lower sympathetic activity. These findings strongly suggest that exercise training may be a therapeutic tool for improving structure and renal function in hypertensive individuals.

  7. Macromolecular prodrugs of ribavirin

    DEFF Research Database (Denmark)

    Smith, Anton Allen Abbotsford; Zuwala, Kaja; Kryger, Mille

    2015-01-01

    -infection increasingly challenging. Herein we report the first design of macromolecular prodrugs (MP) with concurrent success in fighting HIV and alleviating hepatitis (liver inflammation). To achieve this, polymer compositions were systematically screened in a broad range of molar mass and content of ribavirin...

  8. Macromolecular Crystallization in Microgravity

    Science.gov (United States)

    Snell, Edward H.; Helliwell, John R.

    2004-01-01

    The key concepts that attracted crystal growers, macromolecular or solid state, to microgravity research is that density difference fluid flows and sedimentation of the growing crystals are greatly reduced. Thus, defects and flaws in the crystals can be reduced, even eliminated, and crystal volume can be increased. Macromolecular crystallography differs from the field of crystalline semiconductors. For the latter, crystals are harnessed for their electrical behaviors. A crystal of a biological macromolecule is used instead for diffraction experiments (X-ray or neutron) to determine the three-dimensional structure of the macromolecule. The better the internal order of the crystal of a biological macromolecule then the more molecular structure detail that can be extracted. This structural information that enables an understanding of how the molecule functions. This knowledge is changing the biological and chemical sciences with major potential in understanding disease pathologies. Macromolecular structural crystallography in general is a remarkable field where physics, biology, chemistry, and mathematics meet to enable insight to the basic fundamentals of life. In this review, we examine the use of microgravity as an environment to grow macromolecular crystals. We describe the crystallization procedures used on the ground, how the resulting crystals are studied and the knowledge obtained from those crystals. We address the features desired in an ordered crystal and the techniques used to evaluate those features in detail. We then introduce the microgravity environment, the techniques to access that environment, and the theory and evidence behind the use of microgravity for crystallization experiments. We describe how ground-based laboratory techniques have been adapted to microgravity flights and look at some of the methods used to analyze the resulting data. Several case studies illustrate the physical crystal quality improvements and the macromolecular structural

  9. Antimuscarinic-induced convulsions in fasted mice after food intake: No evidence of spontaneous seizures, behavioral changes or neuronal damage.

    Science.gov (United States)

    Enginar, Nurhan; Nurten, Asiye; Türkmen, Aslı Zengin; Gündoğan, Gül İpek; Özünal, Zeynep Güneş

    2017-01-01

    Prolonged or repeated seizures have been shown to cause spontaneous recurrent seizures, increased anxiety‑related behavior, locomotor hyperactivity, impaired functions of learning and memory, and neuronal damage in the hippocampus and other brain regions in animals. Mice and rats treated with antimuscarinic drugs after fasting for two days or less develop convulsions after being allowed to eat ad libitum. To address whether such behavioral and neuroanatomic changes occur following these convulsions, mice treated i.p. with saline (control) or 2.4 mg/kg atropine and given food after 24 h of fasting were grouped according to seizure scores for behavioral and histological analysis. Following convulsions, the occurrence of spontaneous recurrent seizures was observed for 30 days. Motor activity and grooming behavior were assessed in the open field, and memory was assessed using the novel object recognition test 4 and 7 days after onset of convulsions, respectively. Animals allocated for the histological analysis were decapitated 7 days after onset of convulsions and hippocampal slices were evaluated for the percentage of degenerating neurons stained with Fluoro‑Jade C. Spontaneous recurrent seizures, locomotor alterations, anxiety‑related behavior, memory impairment, and neuronal loss in the granular layer of the dentate gyrus were not detected in the animals with seizure score 1-2 or 3-5. These results are in accordance with those related to the absence of behavioral changes, cognitive deficits, and hippocampal neuronal damage after single brief seizures in animals and patients with epilepsy.

  10. Macromolecular crystallization in microgravity

    International Nuclear Information System (INIS)

    Snell, Edward H; Helliwell, John R

    2005-01-01

    Density difference fluid flows and sedimentation of growing crystals are greatly reduced when crystallization takes place in a reduced gravity environment. In the case of macromolecular crystallography a crystal of a biological macromolecule is used for diffraction experiments (x-ray or neutron) so as to determine the three-dimensional structure of the macromolecule. The better the internal order of the crystal then the greater the molecular structure detail that can be extracted. It is this structural information that enables an understanding of how the molecule functions. This knowledge is changing the biological and chemical sciences, with major potential in understanding disease pathologies. In this review, we examine the use of microgravity as an environment to grow macromolecular crystals. We describe the crystallization procedures used on the ground, how the resulting crystals are studied and the knowledge obtained from those crystals. We address the features desired in an ordered crystal and the techniques used to evaluate those features in detail. We then introduce the microgravity environment, the techniques to access that environment and the theory and evidence behind the use of microgravity for crystallization experiments. We describe how ground-based laboratory techniques have been adapted to microgravity flights and look at some of the methods used to analyse the resulting data. Several case studies illustrate the physical crystal quality improvements and the macromolecular structural advances. Finally, limitations and alternatives to microgravity and future directions for this research are covered. Macromolecular structural crystallography in general is a remarkable field where physics, biology, chemistry and mathematics meet to enable insight to the fundamentals of life. As the reader will see, there is a great deal of physics involved when the microgravity environment is applied to crystallization, some of it known, and undoubtedly much yet to

  11. Oxidative stress damage-associated molecular signaling pathways differentiate spontaneous preterm birth and preterm premature rupture of the membranes.

    Science.gov (United States)

    Dutta, Eryn H; Behnia, Faranak; Boldogh, Istvan; Saade, George R; Taylor, Brandie D; Kacerovský, Marian; Menon, Ramkumar

    2016-02-01

    In women with preterm premature rupture of the membranes (PPROM), increased oxidative stress may accelerate premature cellular senescence, senescence-associated inflammation and proteolysis, which may predispose them to rupture. We demonstrate mechanistic differences between preterm birth (PTB) and PPROM by revealing differences in fetal membrane redox status, oxidative stress-induced damage, distinct signaling pathways and senescence activation. Oxidative stress-associated fetal membrane damage and cell cycle arrest determine adverse pregnancy outcomes, such as spontaneous PTB and PPROM. Fetal membranes and amniotic fluid samples were collected from women with PTB and PPROM. Molecular, biochemical and histologic markers were used to document differences in oxidative stress and antioxidant enzyme status, DNA damage, secondary signaling activation by Ras-GTPase and mitogen-activated protein kinases, and activation of senescence between membranes from the two groups. Oxidative stress was higher and antioxidant enzymes were lower in PPROM compared with PTB. PTB membranes had minimal DNA damage and showed activation of Ras-GTPase and ERK/JNK signaling pathway with minimal signs of senescence. PPROM had higher numbers of cells with DNA damage, prosenescence stress kinase (p38 MAPK) activation and signs of senescence. Samples were obtained retrospectively after delivery. The markers of senescence that we tested are specific but are not sufficient to confirm senescence as the pathology in PPROM. Oxidative stress-induced DNA damage and senescence are characteristics of fetal membranes from PPROM, compared with PTB with intact membranes. PTB and PPROM arise from distinct pathophysiologic pathways. Oxidative stress and oxidative stress-induced cellular damages are likely determinants of the mechanistic signaling pathways and phenotypic outcome. This study is supported by developmental funds to Dr R. Menon from the Department of Obstetrics and Gynecology at The University of

  12. Microgravity and Macromolecular Crystallography

    Science.gov (United States)

    Kundrot, Craig E.; Judge, Russell A.; Pusey, Marc L.; Snell, Edward H.; Rose, M. Franklin (Technical Monitor)

    2000-01-01

    Macromolecular crystal growth has been seen as an ideal experiment to make use of the reduced acceleration environment provided by an orbiting spacecraft. The experiments are small, simply operated and have a high potential scientific and economic impact. In this review we examine the theoretical reasons why microgravity should be a beneficial environment for crystal growth and survey the history of experiments on the Space Shuttle Orbiter, on unmanned spacecraft, and on the Mir space station. Finally we outline the direction for optimizing the future use of orbiting platforms.

  13. A CLA enriched diet improves organ damage associated with the metabolic syndrome in spontaneous hypertensive rats

    Energy Technology Data Exchange (ETDEWEB)

    Soto-Rodriguez, I.; Pulido-Camarillo, E.; Hernandez-Diaz, E.; Alexander-Aguilera, A.; Garcia, H.S.

    2011-07-01

    The purpose of this study was to provide evidence that dietary CLA can prevent the pathogenesis of metabolic syndrome in tissue structure, suggesting potential benefits in the onset of this syndrome. Wistar male spontaneous hypertensive rats (SHR), were classified into two groups that were fed a standard diet for eight weeks: one with 7.5% sunflower oil (V-SHR group), and the other with 6% sunflower oil and 1.5% CLA (CLA-SHR group). A control healthy group consisted of Kyoto-Wistar male rats fed the standard diet with 7.5% sunflower oil. The animals were sacrificed, and sections of liver, kidneys and aorta were fixed in 10% formaldehyde, and then stained with Hematoxylin and Eosin. Only in the V-SHR group, the stain of the aorta indicated irregular endothelial morphology; liver parenchyma was characterized by an infiltration of inflammatory neutrophils, fibrosis, thickening of the portal vein epithelium, hepatocyte hyperplasia and steatosis. The renal tissue of this group evidenced hyperplasia in the cells of the endothelial of Bowman's capsule. Abnormal histological changes were not observed in either the control group of the rats fed with CLA, suggesting a protective role of CLA in the onset of metabolic syndrome.

  14. Complex macromolecular chimeras.

    Science.gov (United States)

    Karatzas, Anastasis; Iatrou, Hermis; Hadjichristidis, Nikos; Inoue, Kyouichi; Sugiyama, Kenji; Hirao, Akira

    2008-07-01

    By combining two living polymerizations, anionic and ring opening (ROP), the following novel multiblock multicomponent linear and miktoarm star (micro-star) polymer/polypeptide hybrids (macromolecular chimeras) were synthesized: Linear, PBLL-b-PBLG-b-PS-b-PBLG-b-PBLL; 3micro-stars, (PS)2(PBLG or PBLL), (PS)(PI)(PBLG or PBLL); 4micro-stars, (PS)2[P(alpha-MeS)](PBLG or PBLL), (PS)2(PBLG or PBLL)2 [PS, polystyrene; PI, polyisoprene; P(alpha-MeS), poly(alpha-methylstyrene); PBLG, poly(gamma-benzyl-L-glutamate); and PBLL, poly(-tert-butyloxycarbonyl-L-lysine)]. The procedure involves (a) the synthesis of end- or in-chain amino-functionalized polymers, by anionic polymerization high vacuum techniques and appropriate linking chemistry and (b) the use of the amino groups for the ROP of alpha-amino acid carboxyanhydrides (NCAs). Molecular characterization revealed the high molecular weight and compositional homogeneity of the macromolecular chimeras prepared. The success of the synthesis was based mainly on the high vacuum techniques used for the ROP of NCAs, ensuring the avoidance of unwanted polymerization mechanisms and termination reactions.

  15. A CLA enriched diet improves organ damage associated with the metabolic syndrome in spontaneous hypertensive rats

    Directory of Open Access Journals (Sweden)

    Soto-Rodríguez, Ida

    2011-03-01

    Full Text Available The purpose of this study was to provide evidence that dietary CLA can prevent the pathogenesis of metabolic syndrome in tissue structure, suggesting potential benefits in the onset of this syndrome. Wistar male spontaneous hypertensive rats (SHR, were classified into two groups that were fed a standard diet for eight weeks: one with 7.5% sunflower oil (V-SHR group, and the other with 6% sunflower oil and 1.5% CLA (CLA-SHR group. A control healthy group consisted of Kyoto-Wistar male rats fed the standard diet with 7.5% sunflower oil. The animals were sacrificed, and sections of liver, kidneys and aorta were fixed in 10% formaldehyde, and then stained with Hematoxylin and Eosin. Only in the V-SHR group, the stain of the aorta indicated irregular endothelial morphology; liver parenchyma was characterized by an infiltration of inflammatory neutrophils, fibrosis, thickening of the portal vein epithelium, hepatocyte hyperplasia and steatosis. The renal tissue of this group evidenced hyperplasia in the cells of the endothelial of Bowman´s capsule. Abnormal histological changes were not observed in either the control group or the rats fed with CLA, suggesting a protective role of CLA in the onset of metabolic syndrome.

    El objetivo del presente estudio fue proporcionar evidencia que el CLA dietario puede evitar la patogénesis del síndrome metabólico en la estructura tisular, lo que sugiere beneficios potenciales en el desarrollo de este síndrome. Dos grupos de ratas Wistar macho espontáneamente hipertensas (SHR fueron alimentadas con una dieta normal por 8 semanas: una dieta contenía 7.5% de aceite de girasol (grupo VSHR, y el otro contenía 6% de aceite de girasol y 1.5% de CLA (grupo CLA-SHR. A un grupo testigo sano de ratas macho Kyoto-Wistar les fue proporcionada una dieta normal con 7.5% de aceite de girasol. Los animales fueron sacrificados y se tomaron secciones de hígado, riñones y aorta, las cuales fueron fijadas en formaldeh

  16. Recent advances in macromolecular prodrugs

    DEFF Research Database (Denmark)

    Riber, Camilla Frich; Zelikin, Alexander N.

    2017-01-01

    Macromolecular prodrugs (MP) are high molar mass conjugates, typically carrying several copies of a drug or a drug combination, designed to optimize delivery of the drug, that is — its pharmacokinetics. From its advent several decades ago, design of MP has undergone significant development...

  17. Structure studies of macromolecular systems

    Czech Academy of Sciences Publication Activity Database

    Hašek, Jindřich; Dohnálek, Jan; Skálová, Tereza; Dušková, Jarmila; Kolenko, Petr

    2006-01-01

    Roč. 13, č. 3 (2006), s. 136 ISSN 1211-5894. [Czech and Slovak Crystallographic Colloquium. 22.06.2006-24.06.2006, Grenoble] R&D Projects: GA AV ČR IAA4050811; GA MŠk 1K05008 Keywords : structure * X-ray diffraction * synchrotron Subject RIV: CD - Macromolecular Chemistry http://www. xray .cz/ms/default.htm

  18. Analysis of spontaneous and bleomycin-induced chromosome damage in peripheral lymphocytes of long-haul aircrew members from Argentina

    International Nuclear Information System (INIS)

    Bolzan, Alejandro D.; Bianchi, Martha S.; Gimenez, Esteban M.; Flaque, Maria C. Diaz; Ciancio, Vicente R.

    2008-01-01

    Spontaneous and bleomycin (BLM)-induced chromosomal aberrations in G0 and G2 stages of the cell cycle have been analyzed in peripheral lymphocytes of 21 long-haul aircrew members from Argentina in order to assess BLM-induced clastogenesis as a first approach to determine the DNA repair capacity and thereby the susceptibility to environmental cancers in aircrew. The possibility that occupational exposure of flight personnel to cosmic radiation can induce an adaptive response in their peripheral lymphocytes that can be detected by a subsequent in vitro treatment with BLM was also investigated. For comparison, aberrations were also scored in the lymphocytes of 15 healthy volunteers matched by age, health, sex, drinking and smoking habits to the flight personnel group. Aircrew exhibited a higher frequency of spontaneous dicentrics and ring chromosomes than the control population (p 0.05). However, the aircrew sampled population was almost two times more sensitive to BLM G0 clastogenic effects than controls (p < 0.05). Therefore, our data suggest that chronic exposure of aircrew to cosmic radiation increases the in vitro chromosomal sensitivity of their peripheral lymphocytes to BLM (at least in the G0 stage of the cell cycle), and that occupational exposure of flight personnel to cosmic radiation does not induce an adaptive response to this radiomimetic compound. Our results justify further studies aimed at determine if those aircrew members hypersensitive to BLM are more prone to develop environmental cancer than BLM-insensitive individuals

  19. miR-520 promotes DNA-damage-induced trophoblast cell apoptosis by targeting PARP1 in recurrent spontaneous abortion (RSA).

    Science.gov (United States)

    Dong, Xiujuan; Yang, Long; Wang, Hui

    2017-04-01

    The establishment and maintenance of successful pregnancy mainly depends on trophoblast cells. Their dysfunction has been implicated in recurrent spontaneous abortion (RSA), a major complication of pregnancy. However, the underlying mechanisms of trophoblasts dysfunction remain unclear. DNA-damage-induced cell apoptosis has been reported to play a vital role in cell death. In this study, we identified a novel microRNA (miR-520) in RSA progression via regulating trophoblast cell apoptosis. Microarray analysis showed that miR-520 was highly expressed in villus of RSA patients. By using flow cytometry analysis, we observed miR-520 expression was correlated with human trophoblast cell apoptosis in vitro, along with decreased poly (ADP-ribose) polymerase-1 (PARP1) expression. With the analysis of clinic samples, we observed that miR-520 level was negatively correlated with PARP1 level in RSA villus. In addition, overexpression of PARP1 restored the miR-520-induced trophoblast cell apoptosis in vitro. The status of chromosome in trophoblast implied that miR-520-promoted DNA-damage-induced cell apoptosis to regulate RSA progression. These results indicated that the level of miR-520 might associate with RSA by prompting trophoblast cell apoptosis via PARP1 dependent DNA-damage pathway.

  20. Analysis of spontaneous and bleomycin-induced chromosome damage in peripheral lymphocytes of long-haul aircrew members from Argentina

    Energy Technology Data Exchange (ETDEWEB)

    Bolzan, Alejandro D. [Laboratorio de Citogenetica y Mutagenesis, Instituto Multidisciplinario de Biologia Celular (IMBICE), C.C. 403, 1900 La Plata (Argentina); Miembro de la Carrera del Investigador Cientifico del CONICET (Argentina)], E-mail: abolzan@imbice.org.ar; Bianchi, Martha S. [Laboratorio de Citogenetica y Mutagenesis, Instituto Multidisciplinario de Biologia Celular (IMBICE), C.C. 403, 1900 La Plata (Argentina); Miembro de la Carrera del Investigador Cientifico del CONICET (Argentina); Gimenez, Esteban M.; Flaque, Maria C. Diaz [Laboratorio de Citogenetica y Mutagenesis, Instituto Multidisciplinario de Biologia Celular (IMBICE), C.C. 403, 1900 La Plata (Argentina); Ciancio, Vicente R. [Universidad Nacional de La Plata, Facultad de Ciencias Medicas, 120 y 60, 1900 La Plata (Argentina)

    2008-03-01

    Spontaneous and bleomycin (BLM)-induced chromosomal aberrations in G0 and G2 stages of the cell cycle have been analyzed in peripheral lymphocytes of 21 long-haul aircrew members from Argentina in order to assess BLM-induced clastogenesis as a first approach to determine the DNA repair capacity and thereby the susceptibility to environmental cancers in aircrew. The possibility that occupational exposure of flight personnel to cosmic radiation can induce an adaptive response in their peripheral lymphocytes that can be detected by a subsequent in vitro treatment with BLM was also investigated. For comparison, aberrations were also scored in the lymphocytes of 15 healthy volunteers matched by age, health, sex, drinking and smoking habits to the flight personnel group. Aircrew exhibited a higher frequency of spontaneous dicentrics and ring chromosomes than the control population (p < 0.05). BLM sensitivity test showed that aircrew and controls are equally sensitive to BLM G2 clastogenic effects, since both groups exhibited a similar frequency of chromatid breaks per cell (p > 0.05). However, the aircrew sampled population was almost two times more sensitive to BLM G0 clastogenic effects than controls (p < 0.05). Therefore, our data suggest that chronic exposure of aircrew to cosmic radiation increases the in vitro chromosomal sensitivity of their peripheral lymphocytes to BLM (at least in the G0 stage of the cell cycle), and that occupational exposure of flight personnel to cosmic radiation does not induce an adaptive response to this radiomimetic compound. Our results justify further studies aimed at determine if those aircrew members hypersensitive to BLM are more prone to develop environmental cancer than BLM-insensitive individuals.

  1. Data Mining of Macromolecular Structures.

    Science.gov (United States)

    van Beusekom, Bart; Perrakis, Anastassis; Joosten, Robbie P

    2016-01-01

    The use of macromolecular structures is widespread for a variety of applications, from teaching protein structure principles all the way to ligand optimization in drug development. Applying data mining techniques on these experimentally determined structures requires a highly uniform, standardized structural data source. The Protein Data Bank (PDB) has evolved over the years toward becoming the standard resource for macromolecular structures. However, the process selecting the data most suitable for specific applications is still very much based on personal preferences and understanding of the experimental techniques used to obtain these models. In this chapter, we will first explain the challenges with data standardization, annotation, and uniformity in the PDB entries determined by X-ray crystallography. We then discuss the specific effect that crystallographic data quality and model optimization methods have on structural models and how validation tools can be used to make informed choices. We also discuss specific advantages of using the PDB_REDO databank as a resource for structural data. Finally, we will provide guidelines on how to select the most suitable protein structure models for detailed analysis and how to select a set of structure models suitable for data mining.

  2. Progress in rational methods of cryoprotection in macromolecular crystallography

    International Nuclear Information System (INIS)

    Alcorn, Thomas; Juers, Douglas H.

    2010-01-01

    Measurements of the average thermal contractions (294→72 K) of 26 different cryosolutions are presented and discussed in conjunction with other recent advances in the rational design of protocols for cryogenic cooling in macromolecular crystallography. Cryogenic cooling of macromolecular crystals is commonly used for X-ray data collection both to reduce crystal damage from radiation and to gather functional information by cryogenically trapping intermediates. However, the cooling process can damage the crystals. Limiting cooling-induced crystal damage often requires cryoprotection strategies, which can involve substantial screening of solution conditions and cooling protocols. Here, recent developments directed towards rational methods for cryoprotection are described. Crystal damage is described in the context of the temperature response of the crystal as a thermodynamic system. As such, the internal and external parts of the crystal typically have different cryoprotection requirements. A key physical parameter, the thermal contraction, of 26 different cryoprotective solutions was measured between 294 and 72 K. The range of contractions was 2–13%, with the more polar cryosolutions contracting less. The potential uses of these results in the development of cryocooling conditions, as well as recent developments in determining minimum cryosolution soaking times, are discussed

  3. Visual automated macromolecular model building.

    Science.gov (United States)

    Langer, Gerrit G; Hazledine, Saul; Wiegels, Tim; Carolan, Ciaran; Lamzin, Victor S

    2013-04-01

    Automated model-building software aims at the objective interpretation of crystallographic diffraction data by means of the construction or completion of macromolecular models. Automated methods have rapidly gained in popularity as they are easy to use and generate reproducible and consistent results. However, the process of model building has become increasingly hidden and the user is often left to decide on how to proceed further with little feedback on what has preceded the output of the built model. Here, ArpNavigator, a molecular viewer tightly integrated into the ARP/wARP automated model-building package, is presented that directly controls model building and displays the evolving output in real time in order to make the procedure transparent to the user.

  4. Collagen macromolecular drug delivery systems

    International Nuclear Information System (INIS)

    Gilbert, D.L.

    1988-01-01

    The objective of this study was to examine collagen for use as a macromolecular drug delivery system by determining the mechanism of release through a matrix. Collagen membranes varying in porosity, crosslinking density, structure and crosslinker were fabricated. Collagen characterized by infrared spectroscopy and solution viscosity was determined to be pure and native. The collagen membranes were determined to possess native vs. non-native quaternary structure and porous vs. dense aggregate membranes by electron microscopy. Collagen monolithic devices containing a model macromolecule (inulin) were fabricated. In vitro release rates were found to be linear with respect to t 1/2 and were affected by crosslinking density, crosslinker and structure. The biodegradation of the collagen matrix was also examined. In vivo biocompatibility, degradation and 14 C-inulin release rates were evaluated subcutaneously in rats

  5. Daily Coffee Intake Inhibits Pancreatic Beta Cell Damage and Nonalcoholic Steatohepatitis in a Mouse Model of Spontaneous Metabolic Syndrome, Tsumura-Suzuki Obese Diabetic Mice.

    Science.gov (United States)

    Watanabe, Syunsuke; Takahashi, Tetsuyuki; Ogawa, Hirohisa; Uehara, Hisanori; Tsunematsu, Takaaki; Baba, Hayato; Morimoto, Yuki; Tsuneyama, Koichi

    2017-05-01

    Metabolic syndrome is one of the most important health issues worldwide. Obesity causes insulin resistance, hyperlipidemia, diabetes, and various diseases throughout the body. The liver phenotype, which is called nonalcoholic steatohepatitis (NASH), frequently progresses to hepatocellular carcinoma. We recently established a new animal model, Tsumura-Suzuki obese diabetic (TSOD) mice, which spontaneously exhibit obesity, diabetes, hyperlipidemia, and NASH with liver nodules. We examined the effects of coffee intake on various conditions of the metabolic syndrome using TSOD mice. The daily volume of coffee administered was limited so that it reflected the appropriate quantities consumed in humans. To clarify the effects of the specific components, animals were divided into two coffee-intake groups that included with and without caffeine. Coffee intake did not significantly affect obesity and hyperlipidemia in TSOD mice. In contrast, coffee intake caused various degrees of improvement in the pancreatic beta cell damage and steatohepatitis with liver carcinogenesis. Most of the effects were believed to be caused by a synergistic effect of caffeine with other components such as polyphenols. However, the antifibrotic effects of coffee appeared to be due to the polyphenols rather than the caffeine. A daily habit of drinking coffee could possibly play a role in the prevention of metabolic syndrome.

  6. Macromolecular synthesis in algal cells

    International Nuclear Information System (INIS)

    Ishida, M.R.; Kikuchi, Tadatoshi

    1980-01-01

    The present paper is a review of our experimental results obtained previously on the macromolecular biosyntheses in the cells of blue-green alga Anacystis nidulans as a representative species of prokaryote, and also in those of three species of eukaryotic algae, i.e. Euglena gracilis strain Z, Chlamydomonas reinhardi, and Cyanidium caldarium. In these algal cells, the combined methods consisting of pulse-labelling using 32 P, 3 H- and 14 C-labelled precursors for macromolecules, of their chasing and of the use of inhibitors which block specifically the syntheses of macromolecules such as proteins, RNA and DNA in living cells were very effectively applied for the analyses of the regulatory mechanism in biosyntheses of macromolecules and of the mode of their assembly into the cell structure, especially organelle constituents. Rased on the results obtained thus, the following conclusions are reached: (1) the metabolic pool for syntheses of macromolecules in the cells of prokaryotic blue-green alga is limited to the small extent and such activities couple largely with the photosynthetic mechanism; (2) 70 S ribosomes in the blue-green algal cells are assembled on the surface of thylakoid membranes widely distributed in their cytoplasm; and (3) the cells of eukaryotic unicellular algae used here have biochemical characters specific for already differentiated enzyme system involving in transcription and translation machineries as the same as in higher organisms, but the control mechanism concerning with such macromolecule syntheses are different among each species. (author)

  7. Crystal pathologies in macromolecular crystallography.

    Science.gov (United States)

    Dauter, Zbigniew; Jaskólski, Mariusz

    Macromolecules, such as proteins or nucleic acids, form crystals with a large volume fraction of water, ~50% on average. Apart from typical physical defects and rather trivial poor quality problems, macromolecular crystals, as essentially any crystals, can also suffer from several kinds of pathologies, in which everything seems to be perfect, except that from the structural point of view the interpretation may be very difficult, sometimes even impossible. A frequent nuisance is pseudosymmetry, or non-crystallographic symmetry (NCS), which is particularly nasty when it has translational character. Lattice-translocation defects, also called order-disorder twinning (OD-twinning), occur when molecules are packed regularly in layers but the layers are stacked (without rotation) in two (or more) discrete modes, with a unique translocation vector. Crystal twinning arises when twin domains have different orientations, incompatible with the symmetry of the crystal structure. There are also crystals in which the periodic (lattice) order is broken or absent altogether. When the strict short-range translational order from one unit cell to the next is lost but the long-range order is restored by a periodic modulation, we have a modulated crystal structure. In quasicrystals (not observed for macromolecules yet), the periodic order (in 3D space) is lost completely and the diffraction pattern (which is still discrete) cannot be even indexed using three hkl indices. In addition, there are other physical defects and phenomena (such as high mosaicity, diffraction anisotropy, diffuse scattering, etc.) which make diffraction data processing and structure solution difficult or even impossible.

  8. The design of macromolecular crystallography diffraction experiments

    International Nuclear Information System (INIS)

    Evans, Gwyndaf; Axford, Danny; Owen, Robin L.

    2011-01-01

    Thoughts about the decisions made in designing macromolecular X-ray crystallography experiments at synchrotron beamlines are presented. The measurement of X-ray diffraction data from macromolecular crystals for the purpose of structure determination is the convergence of two processes: the preparation of diffraction-quality crystal samples on the one hand and the construction and optimization of an X-ray beamline and end station on the other. Like sample preparation, a macromolecular crystallography beamline is geared to obtaining the best possible diffraction measurements from crystals provided by the synchrotron user. This paper describes the thoughts behind an experiment that fully exploits both the sample and the beamline and how these map into everyday decisions that users can and should make when visiting a beamline with their most precious crystals

  9. Peanut lectin crystallography and macromolecular structural studies ...

    Indian Academy of Sciences (India)

    2007-08-06

    Aug 6, 2007 ... Home; Journals; Journal of Biosciences; Volume 32; Issue 6. Peanut lectin crystallography and macromolecular structural studies in India. M Vijayan. Perspectives Volume 32 Issue 6 September 2007 pp 1059-1066. Fulltext. Click here to view fulltext PDF. Permanent link:

  10. Automated data collection for macromolecular crystallography.

    Science.gov (United States)

    Winter, Graeme; McAuley, Katherine E

    2011-09-01

    An overview, together with some practical advice, is presented of the current status of the automation of macromolecular crystallography (MX) data collection, with a focus on MX beamlines at Diamond Light Source, UK. Copyright © 2011 Elsevier Inc. All rights reserved.

  11. Status and prospects of macromolecular crystallography

    Indian Academy of Sciences (India)

    Also, computers with extremely large storage capacity and high comput- ing speeds became available at very low cost. These developments made macromolecular crystallogra- phy much like organic chemical crystallography, a task that could be almost completely automated. Initial studies on proteins were mostly on those.

  12. Macromolecular mimicry of nucleic acid and protein

    DEFF Research Database (Denmark)

    Nautrup Pedersen, Gitte; Nyborg, Jens; Clark, Brian F

    1999-01-01

    Although proteins and nucleic acids consist of different chemical components, proteins can mimic structures and possibly also functions of nucleic acids. Recently, structural mimicry was observed between two elongation factors in bacterial protein biosynthesis leading to the introduction of the c......Although proteins and nucleic acids consist of different chemical components, proteins can mimic structures and possibly also functions of nucleic acids. Recently, structural mimicry was observed between two elongation factors in bacterial protein biosynthesis leading to the introduction...... of the concept of macromolecular mimicry. Macromolecular mimicry has further been proposed among initiation and release factors, thereby adding a new element to the description of protein synthesis in bacteria. Such mimicry has also been observed in other biological processes such as autoimmunity, DNA repair...

  13. In situ macromolecular crystallography using microbeams.

    Science.gov (United States)

    Axford, Danny; Owen, Robin L; Aishima, Jun; Foadi, James; Morgan, Ann W; Robinson, James I; Nettleship, Joanne E; Owens, Raymond J; Moraes, Isabel; Fry, Elizabeth E; Grimes, Jonathan M; Harlos, Karl; Kotecha, Abhay; Ren, Jingshan; Sutton, Geoff; Walter, Thomas S; Stuart, David I; Evans, Gwyndaf

    2012-05-01

    Despite significant progress in high-throughput methods in macromolecular crystallography, the production of diffraction-quality crystals remains a major bottleneck. By recording diffraction in situ from crystals in their crystallization plates at room temperature, a number of problems associated with crystal handling and cryoprotection can be side-stepped. Using a dedicated goniometer installed on the microfocus macromolecular crystallography beamline I24 at Diamond Light Source, crystals have been studied in situ with an intense and flexible microfocus beam, allowing weakly diffracting samples to be assessed without a manual crystal-handling step but with good signal to noise, despite the background scatter from the plate. A number of case studies are reported: the structure solution of bovine enterovirus 2, crystallization screening of membrane proteins and complexes, and structure solution from crystallization hits produced via a high-throughput pipeline. These demonstrate the potential for in situ data collection and structure solution with microbeams. © 2012 International Union of Crystallography

  14. Macromolecular Degradation Systems and Cardiovascular Aging.

    Science.gov (United States)

    Nakayama, Hiroyuki; Nishida, Kazuhiko; Otsu, Kinya

    2016-05-13

    Aging-related cardiovascular diseases are a rapidly increasing problem worldwide. Cardiac aging demonstrates progressive decline of diastolic dysfunction of ventricle and increase in ventricular and arterial stiffness accompanied by increased fibrosis stimulated by angiotensin II and proinflammatory cytokines. Reactive oxygen species and multiple signaling pathways on cellular senescence play major roles in the process. Aging is also associated with an alteration in steady state of macromolecular dynamics including a dysfunction of protein synthesis and degradation. Currently, impaired macromolecular degradation is considered to be closely related to enhanced inflammation and be involved in the process and mechanism of cardiac aging. Herein, we review the role and mechanisms of the degradation system of intracellular macromolecules in the process and pathophysiology of cardiovascular aging. © 2016 American Heart Association, Inc.

  15. Highlighting cancer cells with macromolecular probes

    Science.gov (United States)

    Tang, Sicheng; Zhang, Yang; Thapaliya, Ek Raj; Brown, Adrienne S.; Wilson, James N.; Raymo, Françisco M.

    2017-02-01

    Conventional fluorophore-ligand constructs for the detection of cancer cells generally produce relatively weak signals with modest contrast. The inherently low brightness accessible per biding event with the pairing of a single organic fluorophore to a single ligand as well as the contribution of unbound probes to background fluorescence are mainly responsible for these limitations. Our laboratories identified a viable structural design to improve both brightness and contrast. It is based on the integration of activatable fluorophores and targeting ligands within the same macromolecular construct. The chromophoric components are engineered to emit bright fluorescence exclusively in acidic environments. The targeting agents are designed to bind complementary receptors overexpressed on the surface of cancer cells and allow internalization of the macromolecules into acidic organelles. As a result of these properties, our macromolecular probes switch their intense emission on exclusively in the intracellular space of target cells with minimal background fluorescence from the extracellular matrix. In fact, these operating principles translate into a 170-fold enhancement in brightness, relative to equivalent but isolated chromophoric components, and a 3-fold increase in contrast, relative to model but non-activatable fluorophores. Thus, our macromolecular probes might ultimately evolve into valuable analytical tools to highlight cancer cells with optimal signal-to-noise ratios in a diversity of biomedical applications.

  16. Spontaneous pneumothorax

    Directory of Open Access Journals (Sweden)

    Davari R

    1996-07-01

    Full Text Available A case with bilateral spontaneous pneumothorax was presented. Etiology, mechanism, and treatment were discussed on the review of literature. Spontaneous Pneumothorax is a clinical entity resulting from a sudden non traumatic rupture of the lung. Biach reported in 1880 that 78% of 916 patients with spontaneous pneumothorax had tuberculosis. Kjergaard emphasized 1932 the primary importance of subpleural bleb disease. Currently the clinical spectrum of spontaneous pneumothorax seems to have entered a third era with the recognition of the interstitial lung disease and AIDS as a significant etiology. Standard treatment is including: observation, thoracocentesis, tube thoracostomy. Chemical pleurodesis, bullectomy or wedge resection of lung with pleural abrasion and occasionally pleurectomy. Little information has been reported regarding the efficacy of such treatment in spontaneous pneumothorax secondary to non bleb disease

  17. A public database of macromolecular diffraction experiments.

    Science.gov (United States)

    Grabowski, Marek; Langner, Karol M; Cymborowski, Marcin; Porebski, Przemyslaw J; Sroka, Piotr; Zheng, Heping; Cooper, David R; Zimmerman, Matthew D; Elsliger, Marc André; Burley, Stephen K; Minor, Wladek

    2016-11-01

    The low reproducibility of published experimental results in many scientific disciplines has recently garnered negative attention in scientific journals and the general media. Public transparency, including the availability of `raw' experimental data, will help to address growing concerns regarding scientific integrity. Macromolecular X-ray crystallography has led the way in requiring the public dissemination of atomic coordinates and a wealth of experimental data, making the field one of the most reproducible in the biological sciences. However, there remains no mandate for public disclosure of the original diffraction data. The Integrated Resource for Reproducibility in Macromolecular Crystallography (IRRMC) has been developed to archive raw data from diffraction experiments and, equally importantly, to provide related metadata. Currently, the database of our resource contains data from 2920 macromolecular diffraction experiments (5767 data sets), accounting for around 3% of all depositions in the Protein Data Bank (PDB), with their corresponding partially curated metadata. IRRMC utilizes distributed storage implemented using a federated architecture of many independent storage servers, which provides both scalability and sustainability. The resource, which is accessible via the web portal at http://www.proteindiffraction.org, can be searched using various criteria. All data are available for unrestricted access and download. The resource serves as a proof of concept and demonstrates the feasibility of archiving raw diffraction data and associated metadata from X-ray crystallographic studies of biological macromolecules. The goal is to expand this resource and include data sets that failed to yield X-ray structures in order to facilitate collaborative efforts that will improve protein structure-determination methods and to ensure the availability of `orphan' data left behind for various reasons by individual investigators and/or extinct structural genomics

  18. Development of macromolecular prodrug for rheumatoid arthritis.

    Science.gov (United States)

    Yuan, Fang; Quan, Ling-dong; Cui, Liao; Goldring, Steven R; Wang, Dong

    2012-09-01

    Rheumatoid arthritis (RA) is a chronic autoimmune disease that is considered to be one of the major public health problems worldwide. The development of therapies that target tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and co-stimulatory pathways that regulate the immune system have revolutionized the care of patients with RA. Despite these advances, many patients continue to experience symptomatic and functional impairment. To address this issue, more recent therapies that have been developed are designed to target intracellular signaling pathways involved in immunoregulation. Though this approach has been encouraging, there have been major challenges with respect to off-target organ side effects and systemic toxicities related to the widespread distribution of these signaling pathways in multiple cell types and tissues. These limitations have led to an increasing interest in the development of strategies for the macromolecularization of anti-rheumatic drugs, which could target them to the inflamed joints. This approach enhances the efficacy of the therapeutic agent with respect to synovial inflammation, while markedly reducing non-target organ adverse side effects. In this manuscript, we provide a comprehensive overview of the rational design and optimization of macromolecular prodrugs for treatment of RA. The superior and the sustained efficacy of the prodrug may be partially attributed to their Extravasation through Leaky Vasculature and subsequent Inflammatory cell-mediated Sequestration (ELVIS) in the arthritic joints. This biologic process provides a plausible mechanism, by which macromolecular prodrugs preferentially target arthritic joints and illustrates the potential benefits of applying this therapeutic strategy to the treatment of other inflammatory diseases. Copyright © 2012 Elsevier B.V. All rights reserved.

  19. Celebrating macromolecular crystallography: A personal perspective

    Directory of Open Access Journals (Sweden)

    Abad-Zapatero, Celerino

    2015-04-01

    Full Text Available The twentieth century has seen an enormous advance in the knowledge of the atomic structures that surround us. The discovery of the first crystal structures of simple inorganic salts by the Braggs in 1914, using the diffraction of X-rays by crystals, provided the critical elements to unveil the atomic structure of matter. Subsequent developments in the field leading to macromolecular crystallography are presented with a personal perspective, related to the cultural milieu of Spain in the late 1950’s. The journey of discovery of the author, as he developed professionally, is interwoven with the expansion of macromolecular crystallography from the first proteins (myoglobin, hemoglobin to the ‘coming of age’ of the field in 1971 and the discoveries that followed, culminating in the determination of the structure of the ribosomes at the turn of the century. A perspective is presented exploring the future of the field and also a reflection about the future generations of Spanish scientists.El siglo XX ha sido testigo del increíble avance que ha experimentado el conocimiento de la estructura atómica de la materia que nos rodea. El descubrimiento de las primeras estructuras atómicas de sales inorgánicas por los Bragg en 1914, empleando difracción de rayos X con cristales, proporcionó los elementos clave para alcanzar tal conocimiento. Posteriores desarrollos en este campo, que condujeron a la cristalografía macromolecular, se presentan aquí desde una perspectiva personal, relacionada con el contexto cultural de la España de la década de los 50. La experiencia del descubrimiento científico, durante mi desarrollo profesional, se integra en el desarrollo de la cristalografía macromolecular, desde las primeras proteínas (míoglobina y hemoglobina, hasta su madurez en 1971 que, con los posteriores descubrimientos, culmina con la determinación del la estructura del ribosoma. Asimismo, se explora el futuro de esta disciplina y se

  20. Clustering procedures for the optimal selection of data sets from multiple crystals in macromolecular crystallography

    International Nuclear Information System (INIS)

    Foadi, James; Aller, Pierre; Alguel, Yilmaz; Cameron, Alex; Axford, Danny; Owen, Robin L.; Armour, Wes; Waterman, David G.; Iwata, So; Evans, Gwyndaf

    2013-01-01

    A systematic approach to the scaling and merging of data from multiple crystals in macromolecular crystallography is introduced and explained. The availability of intense microbeam macromolecular crystallography beamlines at third-generation synchrotron sources has enabled data collection and structure solution from microcrystals of <10 µm in size. The increased likelihood of severe radiation damage where microcrystals or particularly sensitive crystals are used forces crystallographers to acquire large numbers of data sets from many crystals of the same protein structure. The associated analysis and merging of multi-crystal data is currently a manual and time-consuming step. Here, a computer program, BLEND, that has been written to assist with and automate many of the steps in this process is described. It is demonstrated how BLEND has successfully been used in the solution of a novel membrane protein

  1. Clustering procedures for the optimal selection of data sets from multiple crystals in macromolecular crystallography

    Energy Technology Data Exchange (ETDEWEB)

    Foadi, James [Diamond Light Source, Harwell Science and Innovation Campus, Didcot, Oxfordshire OX11 0DE (United Kingdom); Imperial College, London SW7 2AZ (United Kingdom); Aller, Pierre [Diamond Light Source, Harwell Science and Innovation Campus, Didcot, Oxfordshire OX11 0DE (United Kingdom); Alguel, Yilmaz; Cameron, Alex [Imperial College, London SW7 2AZ (United Kingdom); Axford, Danny; Owen, Robin L. [Diamond Light Source, Harwell Science and Innovation Campus, Didcot, Oxfordshire OX11 0DE (United Kingdom); Armour, Wes [Oxford e-Research Centre (OeRC), Keble Road, Oxford OX1 3QG (United Kingdom); Waterman, David G. [Research Complex at Harwell (RCaH), Harwell Science and Innovation Campus, Didcot, Oxfordshire OX11 0FA (United Kingdom); Iwata, So [Diamond Light Source, Harwell Science and Innovation Campus, Didcot, Oxfordshire OX11 0DE (United Kingdom); Imperial College, London SW7 2AZ (United Kingdom); Evans, Gwyndaf, E-mail: gwyndaf.evans@diamond.ac.uk [Diamond Light Source, Harwell Science and Innovation Campus, Didcot, Oxfordshire OX11 0DE (United Kingdom)

    2013-08-01

    A systematic approach to the scaling and merging of data from multiple crystals in macromolecular crystallography is introduced and explained. The availability of intense microbeam macromolecular crystallography beamlines at third-generation synchrotron sources has enabled data collection and structure solution from microcrystals of <10 µm in size. The increased likelihood of severe radiation damage where microcrystals or particularly sensitive crystals are used forces crystallographers to acquire large numbers of data sets from many crystals of the same protein structure. The associated analysis and merging of multi-crystal data is currently a manual and time-consuming step. Here, a computer program, BLEND, that has been written to assist with and automate many of the steps in this process is described. It is demonstrated how BLEND has successfully been used in the solution of a novel membrane protein.

  2. In situ macromolecular crystallography using microbeams

    International Nuclear Information System (INIS)

    Axford, Danny; Owen, Robin L.; Aishima, Jun; Foadi, James; Morgan, Ann W.; Robinson, James I.; Nettleship, Joanne E.; Owens, Raymond J.; Moraes, Isabel; Fry, Elizabeth E.; Grimes, Jonathan M.; Harlos, Karl; Kotecha, Abhay; Ren, Jingshan; Sutton, Geoff; Walter, Thomas S.; Stuart, David I.; Evans, Gwyndaf

    2012-01-01

    A sample environment for mounting crystallization trays has been developed on the microfocus beamline I24 at Diamond Light Source. The technical developments and several case studies are described. Despite significant progress in high-throughput methods in macromolecular crystallography, the production of diffraction-quality crystals remains a major bottleneck. By recording diffraction in situ from crystals in their crystallization plates at room temperature, a number of problems associated with crystal handling and cryoprotection can be side-stepped. Using a dedicated goniometer installed on the microfocus macromolecular crystallography beamline I24 at Diamond Light Source, crystals have been studied in situ with an intense and flexible microfocus beam, allowing weakly diffracting samples to be assessed without a manual crystal-handling step but with good signal to noise, despite the background scatter from the plate. A number of case studies are reported: the structure solution of bovine enterovirus 2, crystallization screening of membrane proteins and complexes, and structure solution from crystallization hits produced via a high-throughput pipeline. These demonstrate the potential for in situ data collection and structure solution with microbeams

  3. EIGER detector: application in macromolecular crystallography.

    Science.gov (United States)

    Casanas, Arnau; Warshamanage, Rangana; Finke, Aaron D; Panepucci, Ezequiel; Olieric, Vincent; Nöll, Anne; Tampé, Robert; Brandstetter, Stefan; Förster, Andreas; Mueller, Marcus; Schulze-Briese, Clemens; Bunk, Oliver; Wang, Meitian

    2016-09-01

    The development of single-photon-counting detectors, such as the PILATUS, has been a major recent breakthrough in macromolecular crystallography, enabling noise-free detection and novel data-acquisition modes. The new EIGER detector features a pixel size of 75 × 75 µm, frame rates of up to 3000 Hz and a dead time as low as 3.8 µs. An EIGER 1M and EIGER 16M were tested on Swiss Light Source beamlines X10SA and X06SA for their application in macromolecular crystallography. The combination of fast frame rates and a very short dead time allows high-quality data acquisition in a shorter time. The ultrafine ϕ-slicing data-collection method is introduced and validated and its application in finding the optimal rotation angle, a suitable rotation speed and a sufficient X-ray dose are presented. An improvement of the data quality up to slicing at one tenth of the mosaicity has been observed, which is much finer than expected based on previous findings. The influence of key data-collection parameters on data quality is discussed.

  4. Scientific Opinion on the substantiation of a health claim related to coffee C21, a coffee standardised by its content of caffeoylquinic acids, trigonelline and N-methylpyridinium, and reduction of DNA damage by decreasing spontaneous DNA strand breaks

    DEFF Research Database (Denmark)

    Tetens, Inge

    2015-01-01

    Following an application from Tchibo GmbH, submitted for authorisation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 via the Competent Authority of Germany, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked to deliver an opinion on the scie......Following an application from Tchibo GmbH, submitted for authorisation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 via the Competent Authority of Germany, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked to deliver an opinion...... on the scientific substantiation of a health claim related to coffee C21 and reduction of DNA damage by decreasing spontaneous DNA strand breaks. The scope of the application was proposed to fall under a health claim based on newly developed scientific evidence. Coffee C21, a coffee standardised by its content...... intervention study showed that daily consumption of coffee C21 (750 ml/day) for four weeks decreased spontaneous DNA strand breaks in habitual coffee drinkers after coffee withdrawal over the previous four weeks, but that no other human studies in which these results have been replicated were provided...

  5. The role of macromolecular stability in desiccation tolerance

    NARCIS (Netherlands)

    Wolkers, W.F.

    1998-01-01

    The work presented in this thesis concerns a study on the molecular interactions that play a role in the macromolecular stability of desiccation-tolerant higher plant organs. Fourier transform infrared microspectroscopy was used as the main experimental technique to assess macromolecular

  6. Spontaneous deregulation

    NARCIS (Netherlands)

    Edelman, Benjamin; Geradin, Damien

    Platform businesses such as Airbnb and Uber have risen to success partly by sidestepping laws and regulations that encumber their traditional competitors. Such rule flouting is what the authors call “spontaneous private deregulation,” and it’s happening in a growing number of industries. The authors

  7. Challenges and Perspectives in the Macromolecular Flatland.

    Science.gov (United States)

    Servalli, Marco

    2017-06-28

    Polymer chemistry has recently welcomed a new addition to its field: the planar macromolecules known as two-dimensional polymers (2DPs). These topologically planar and crystalline monolayer covalent sheets are reminiscent of molecular fishermen's nets and apart from being conceptually very interesting for the field of macro-molecular chemistry, they also show some potential applications as novel 2D materials. This article reviews how the field has developed five years after the first 2DP was synthesised in 2012. After a brief historical introduction, the main synthetic approaches will be discussed providing concrete examples of 2DPs and highlighting the challenges associated with the synthesis and especially structural characterisation of these fascinating macro-molecules. Finally an overview on their potential applications such as membranes for gas separation, rewritable molecular paper and miniaturisation of optical devices will be presented.

  8. Functional Sub-states by High-pressure Macromolecular Crystallography.

    Science.gov (United States)

    Dhaussy, Anne-Claire; Girard, Eric

    2015-01-01

    At the molecular level, high-pressure perturbation is of particular interest for biological studies as it allows trapping conformational substates. Moreover, within the context of high-pressure adaptation of deep-sea organisms, it allows to decipher the molecular determinants of piezophily. To provide an accurate description of structural changes produced by pressure in a macromolecular system, developments have been made to adapt macromolecular crystallography to high-pressure studies. The present chapter is an overview of results obtained so far using high-pressure macromolecular techniques, from nucleic acids to virus capsid through monomeric as well as multimeric proteins.

  9. Study of macromolecular synthesis in a range of radiation sensitive mutants of yeast

    Energy Technology Data Exchange (ETDEWEB)

    Piperakis, S.M. (Liverpool Univ. (UK)); Parry, E.M. (University Coll. of Swansea (UK))

    1982-01-01

    The comprehensive study of macromolecular synthesis in the rad mutants of Saccharomyces cerevisiae which has been presented reveals no direct correlation between radiation sensitivity and DNA contents. Although the rad mutants are different from one another in their response to U.V.-light, unlike 2nL, their DNA, RNA, and protein content have been found to be virtually identical. (2nL is a diploid strain characterized by a deficiency of approximately 18% in the total cellular DNA content. This strain of yeast has also been shown to be x-ray sensitive and defective in the regulation of repair of U.V. light-induced cell damage).

  10. An upper limit for macromolecular crowding effects

    Directory of Open Access Journals (Sweden)

    Miklos Andrew C

    2011-05-01

    Full Text Available Abstract Background Solutions containing high macromolecule concentrations are predicted to affect a number of protein properties compared to those properties in dilute solution. In cells, these macromolecular crowders have a large range of sizes and can occupy 30% or more of the available volume. We chose to study the stability and ps-ns internal dynamics of a globular protein whose radius is ~2 nm when crowded by a synthetic microgel composed of poly(N-isopropylacrylamide-co-acrylic acid with particle radii of ~300 nm. Results Our studies revealed no change in protein rotational or ps-ns backbone dynamics and only mild (~0.5 kcal/mol at 37°C, pH 5.4 stabilization at a volume occupancy of 70%, which approaches the occupancy of closely packing spheres. The lack of change in rotational dynamics indicates the absence of strong crowder-protein interactions. Conclusions Our observations are explained by the large size discrepancy between the protein and crowders and by the internal structure of the microgels, which provide interstitial spaces and internal pores where the protein can exist in a dilute solution-like environment. In summary, microgels that interact weakly with proteins do not strongly influence protein dynamics or stability because these large microgels constitute an upper size limit on crowding effects.

  11. Pulsatile Gating of Giant Vesicles Containing Macromolecular Crowding Agents Induced by Colligative Nonideality.

    Science.gov (United States)

    Su, Wan-Chih; Gettel, Douglas L; Chabanon, Morgan; Rangamani, Padmini; Parikh, Atul N

    2018-01-17

    The ability of large macromolecules to exhibit nontrivial deviations in colligative properties of their aqueous solutions is well-appreciated in polymer physics. Here, we show that this colligative nonideality subjects giant lipid vesicles containing inert macromolecular crowding agents to osmotic pressure differentials when bathed in small-molecule osmolytes at comparable concentrations. The ensuing influx of water across the semipermeable membrane induces characteristic swell-burst cycles: here, cyclical and damped oscillations in size, tension, and membrane phase separation occur en route to equilibration. Mediated by synchronized formation of transient pores, these cycles orchestrate pulsewise ejection of macromolecules from the vesicular interior reducing the osmotic differential in a stepwise manner. These experimental findings are fully corroborated by a theoretical model derived by explicitly incorporating the contributions of the solution viscosity, solute diffusivity, and the colligative nonideality of the osmotic pressure in a previously reported continuum description. Simulations based on this model account for the differences in the details of the noncolligatively induced swell-burst cycles, including numbers and periods of the repeating cycles, as well as pore lifetimes. Taken together, our observations recapitulate behaviors of vesicles and red blood cells experiencing sudden osmotic shocks due to large (hundreds of osmolars) differences in the concentrations of small molecule osmolytes and link intravesicular macromolecular crowding with membrane remodeling. They further suggest that any tendency for spontaneous overcrowding in single giant vesicles is opposed by osmotic stresses and requires independent specific interactions, such as associative chemical interactions or those between the crowders and the membrane boundary.

  12. JBlulce Data Acquisition Software for Macromolecular Crystallography

    Energy Technology Data Exchange (ETDEWEB)

    2010-06-01

    JBlulce (Java Beam Line Universal Integrated Configuration Environment is a data acquisition software for macromolecular crystallography conforming user interface of the SSRL Blulce that has become a de-factor standard in the field. Besides this interface conformity, JBlulce is a unique system in terms of architecture, speec, capability and osftware implementation. It features only two software layers, the JBlulce clients and the EPICS servers, as compared to three layers present in Blulc and most of similar systems. This layers reduction provides a faster communication with hardware and an easier access to advanced hardware capabilities like on-the-fly scanning. Then JBlulc clients are designed to operate in parallel with the other beamline controls which streamlines the tasks performed by staff such as beamline preparation, maitenance, audting and user assistance. Another distinction is the deployment of multiple plugins that can be written in any programming languag thus involving more staff into the development. further on, JBlulce makes use of unified motion controls allowing for easy scanning and optimizing of any beamline component. Finally, the graphic interface is implemented in Java making full use of rich Java libraries and Jave IDE for debugging. to compare, Blulce user interface is implemented with aging Tcl/tk language providing very restricted capabilities. JBlulce makes full use of the industrial power and wide drivers selection of EPICS in controlling hardware; all hardware commuication is routed via multiple EPICS servers residing on local area network. JBlulce also includes several EPICS State Notation servers aimed at making hardware communication more robust. Besides using EPICS for controlling hardware, JBlulce extensively uses EPICS databases for efficien communications between multiple instances of JBlulce clients and JBlulce pplugins that can run in parallel on different computers. All of the above makes JBlulce one of the biggest and most

  13. Spontaneous isolated celiac artery dissection

    Directory of Open Access Journals (Sweden)

    Tuba Cimilli Ozturk

    2011-01-01

    Full Text Available Dyspepsia with mild, stabbing epigastric discomfort without history of trauma is a very common symptom that emergency physicians see in their daily practice. Vascular emergencies, mostly the aortic dissection and aneurysm, are always described in the differential diagnosis with persistent symptoms. Isolated celiac artery dissection occurring spontaneously is a very rare diagnosis. The involvement of branch vessels is generally observed and patients show various clinical signs and symptoms according to the involved branch vessel. Here we are presenting a case with spontaneous isolated celiac artery dissection, without any branch vessel involvement or visceral damage, detected by computed tomography scans taken on admission.

  14. Complex Macromolecular Architectures by Living Cationic Polymerization

    KAUST Repository

    Alghamdi, Reem D.

    2015-05-01

    Poly (vinyl ether)-based graft polymers have been synthesized by the combination of living cationic polymerization of vinyl ethers with other living or controlled/ living polymerization techniques (anionic and ATRP). The process involves the synthesis of well-defined homopolymers (PnBVE) and co/terpolymers [PnBVE-b-PCEVE-b-PSiDEGVE (ABC type) and PSiDEGVE-b-PnBVE-b-PSiDEGVE (CAC type)] by sequential living cationic polymerization of n-butyl vinyl ether (nBVE), 2-chloroethyl vinyl ether (CEVE) and tert-butyldimethylsilyl ethylene glycol vinyl ether (SiDEGVE), using mono-functional {[n-butoxyethyl acetate (nBEA)], [1-(2-chloroethoxy) ethyl acetate (CEEA)], [1-(2-(2-(t-butyldimethylsilyloxy)ethoxy) ethoxy) ethyl acetate (SiDEGEA)]} or di-functional [1,4-cyclohexanedimethanol di(1-ethyl acetate) (cHMDEA), (VEMOA)] initiators. The living cationic polymerizations of those monomers were conducted in hexane at -20 0C using Et3Al2Cl3 (catalyst) in the presence of 1 M AcOEt base.[1] The PCEVE segments of the synthesized block terpolymers were then used to react with living macroanions (PS-DPE-Li; poly styrene diphenyl ethylene lithium) to afford graft polymers. The quantitative desilylation of PSiDEGVE segments by n-Bu4N+F- in THF at 0 °C led to graft co- and terpolymers in which the polyalcohol is the outer block. These co-/terpolymers were subsequently subjected to “grafting-from” reactions by atom transfer radical polymerization (ATRP) of styrene to afford more complex macromolecular architectures. The base assisted living cationic polymerization of vinyl ethers were also used to synthesize well-defined α-hydroxyl polyvinylether (PnBVE-OH). The resulting polymers were then modified into an ATRP macro-initiator for the synthesis of well-defined block copolymers (PnBVE-b-PS). Bifunctional PnBVE with terminal malonate groups was also synthesized and used as a precursor for more complex architectures such as H-shaped block copolymer by “grafting-from” or

  15. Macromolecular Antioxidants and Dietary Fiber in Edible Seaweeds.

    Science.gov (United States)

    Sanz-Pintos, Nerea; Pérez-Jiménez, Jara; Buschmann, Alejandro H; Vergara-Salinas, José Rodrigo; Pérez-Correa, José Ricardo; Saura-Calixto, Fulgencio

    2017-02-01

    Seaweeds are rich in different bioactive compounds with potential uses in drugs, cosmetics and the food industry. The objective of this study was to analyze macromolecular antioxidants or nonextractable polyphenols, in several edible seaweed species collected in Chile (Gracilaria chilensis, Callophyllis concepcionensis, Macrocystis pyrifera, Scytosyphon lomentaria, Ulva sp. and Enteromorpha compressa), including their 1st HPLC characterization. Macromolecular antioxidants are commonly ignored in studies of bioactive compounds. They are associated with insoluble dietary fiber and exhibit significant biological activity, with specific features that are different from those of both dietary fiber and extractable polyphenols. We also evaluated extractable polyphenols and dietary fiber, given their relationship with macromolecular antioxidants. Our results show that macromolecular antioxidants are a major polyphenol fraction (averaging 42% to total polyphenol content), with hydroxycinnamic acids, hydroxybenzoic acids and flavonols being the main constituents. This fraction also showed remarkable antioxidant capacity, as determined by 2 complementary assays. The dietary fiber content was over 50% of dry weight, with some samples exhibiting the target proportionality between soluble and insoluble dietary fiber for adequate nutrition. Overall, our data show that seaweed could be an important source of commonly ignored macromolecular antioxidants. © 2017 Institute of Food Technologists®.

  16. Macromolecular crystallography beamline X25 at the NSLS

    International Nuclear Information System (INIS)

    Héroux, Annie; Allaire, Marc; Buono, Richard; Cowan, Matthew L.; Dvorak, Joseph; Flaks, Leon; LaMarra, Steven; Myers, Stuart F.; Orville, Allen M.; Robinson, Howard H.; Roessler, Christian G.; Schneider, Dieter K.; Shea-McCarthy, Grace; Skinner, John M.; Skinner, Michael; Soares, Alexei S.; Sweet, Robert M.; Berman, Lonny E.

    2014-01-01

    A description of the upgraded beamline X25 at the NSLS, operated by the PXRR and the Photon Sciences Directorate serving the Macromolecular Crystallography community, is presented. Beamline X25 at the NSLS is one of the five beamlines dedicated to macromolecular crystallography operated by the Brookhaven National Laboratory Macromolecular Crystallography Research Resource group. This mini-gap insertion-device beamline has seen constant upgrades for the last seven years in order to achieve mini-beam capability down to 20 µm × 20 µm. All major components beginning with the radiation source, and continuing along the beamline and its experimental hutch, have changed to produce a state-of-the-art facility for the scientific community

  17. Adaptation to high temperatures through macromolecular dynamics by neutron scattering.

    Science.gov (United States)

    Tehei, Moeava; Zaccai, Giuseppe

    2007-08-01

    Work on the relationship between hyperthermophile protein dynamics, stability and activity is reviewed. Neutron spectroscopy has been applied to measure and compare the macromolecular dynamics of various hyperthermophilic and mesophilic proteins, under different conditions. First, molecular dynamics have been analyzed for the hyperthermophile malate dehydrogenase from Methanococcus jannaschii and a mesophilic homologue, the lactate dehydrogenase from Oryctolagus cunniculus (rabbit) muscle. The neutron scattering approach has provided independent measurements of the global flexibility and structural resilience of each protein, and it has been demonstrated that macromolecular dynamics represents one of the molecular mechanisms of thermoadaptation. The resilience was found to be higher for the hyperthermophilic protein, thus ensuring similar flexibilities in both enzymes at their optimal activity temperature. Second, the neutron method has been developed to quantify the average macromolecular flexibility and resilience within the natural crowded environment of the cell, and mean macromolecular motions have been measured in vivo in psychrophile, mesophile, thermophile and hyperthermophile bacteria. The macromolecular resilience in bacteria was found to increase with adaptation to high temperatures, whereas flexibility was maintained within narrow limits, independent of physiological temperature for all cells in their active state. Third, macromolecular motions have been measured in free and immobilized dihydrofolate reductase from Escherichia coli. The immobilized mesophilic enzyme has increased stability and decreased activity, so that its properties are changed to resemble those of a thermophilic enzyme. Quasi-elastic neutron scattering measurements have also been performed to probe the protein motions. Compared to the free enzyme, the average height of the activation free energy barrier to local motions was found to be increased by 0.54 kcal.mol(-1) in the

  18. Metabolite Damage and Metabolite Damage Control in Plants

    Energy Technology Data Exchange (ETDEWEB)

    Hanson, Andrew D. [Horticultural Sciences Department and; Henry, Christopher S. [Mathematics and Computer Science Division, Argonne National Laboratory, Argonne, Illinois 60439, email:; Computation Institute, University of Chicago, Chicago, Illinois 60637; Fiehn, Oliver [Genome Center, University of California, Davis, California 95616, email:; de Crécy-Lagard, Valérie [Microbiology and Cell Science Department, University of Florida, Gainesville, Florida 32611, email: ,

    2016-04-29

    It is increasingly clear that (a) many metabolites undergo spontaneous or enzyme-catalyzed side reactions in vivo, (b) the damaged metabolites formed by these reactions can be harmful, and (c) organisms have biochemical systems that limit the buildup of damaged metabolites. These damage-control systems either return a damaged molecule to its pristine state (metabolite repair) or convert harmful molecules to harmless ones (damage preemption). Because all organisms share a core set of metabolites that suffer the same chemical and enzymatic damage reactions, certain damage-control systems are widely conserved across the kingdoms of life. Relatively few damage reactions and damage-control systems are well known. Uncovering new damage reactions and identifying the corresponding damaged metabolites, damage-control genes, and enzymes demands a coordinated mix of chemistry, metabolomics, cheminformatics, biochemistry, and comparative genomics. This review illustrates the above points using examples from plants, which are at least as prone to metabolite damage as other organisms.

  19. Non-contact luminescence lifetime cryothermometry for macromolecular crystallography.

    Science.gov (United States)

    Mykhaylyk, V B; Wagner, A; Kraus, H

    2017-05-01

    Temperature is a very important parameter when aiming to minimize radiation damage to biological samples during experiments that utilize intense ionizing radiation. A novel technique for remote, non-contact, in situ monitoring of the protein crystal temperature has been developed for the new I23 beamline at the Diamond Light Source, a facility dedicated to macromolecular crystallography (MX) with long-wavelength X-rays. The temperature is derived from the temperature-dependent decay time constant of luminescence from a minuscule scintillation sensor (<0.05 mm 3 ) located in very close proximity to the sample under test. In this work the underlying principle of cryogenic luminescence lifetime thermometry is presented, the features of the detection method and the choice of temperature sensor are discussed, and it is demonstrated how the temperature monitoring system was integrated within the viewing system of the endstation used for the visualization of protein crystals. The thermometry system was characterized using a Bi 4 Ge 3 O 12 crystal scintillator that exhibits good responsivity of the decay time constant as a function of temperature over a wide range (8-270 K). The scintillation sensor was calibrated and the uncertainty of the temperature measurements over the primary operation temperature range of the beamline (30-150 K) was assessed to be ±1.6 K. It has been shown that the temperature of the sample holder, measured using the luminescence sensor, agrees well with the expected value. The technique was applied to characterize the thermal performance of different sample mounts that have been used in MX experiments at the I23 beamline. The thickness of the mount is shown to have the greatest impact upon the temperature distribution across the sample mount. Altogether, these tests and findings demonstrate the usefulness of the thermometry system in highlighting the challenges that remain to be addressed for the in-vacuum MX experiment to become a

  20. A sensor for quantification of macromolecular crowding in living cells

    NARCIS (Netherlands)

    Boersma, Arnold J; Zuhorn, Inge S; Poolman, Bert

    Macromolecular crowding in cells influences processes such as folding, association and diffusion of proteins and polynucleic acids. Direct spatiotemporal readout of crowding would be a powerful approach for unraveling the structure of the cytoplasm and determining the impact of excluded volume on

  1. Terminology and nomenclature for macromolecular rotaxanes and pseudorotaxanes (IUPAC Recommendations 2012)

    Czech Academy of Sciences Publication Activity Database

    Vohlídal, J.; Wilks, E. S.; Yerin, A.; Fradet, A.; Hellwich, K. H.; Hodge, P.; Kahovec, Jaroslav; Mormann, W.; Stepto, R. F. T.

    2012-01-01

    Roč. 84, č. 10 (2012), s. 2135-2165 ISSN 0033-4545 Institutional research plan: CEZ:AV0Z40500505 Keywords : IUPAC Chemical Nomenclature and Structure Representation Division * macromolecular pseudorotaxanes * macromolecular rotaxanes Subject RIV: CD - Macromolecular Chemistry Impact factor: 3.386, year: 2012

  2. Macromolecular metamorphosis via stimulus-induced transformations of polymer architecture.

    Science.gov (United States)

    Sun, Hao; Kabb, Christopher P; Dai, Yuqiong; Hill, Megan R; Ghiviriga, Ion; Bapat, Abhijeet P; Sumerlin, Brent S

    2017-08-01

    Macromolecular architecture plays a pivotal role in determining the properties of polymers. When designing polymers for specific applications, it is not only the size of a macromolecule that must be considered, but also its shape. In most cases, the topology of a polymer is a static feature that is inalterable once synthesized. Using reversible-covalent chemistry to prompt the disconnection of chemical bonds and the formation of new linkages in situ, we report polymers that undergo dramatic topological transformations via a process we term macromolecular metamorphosis. Utilizing this technique, a linear amphiphilic block copolymer or hyperbranched polymer undergoes 'metamorphosis' into comb, star and hydrophobic block copolymer architectures. This approach was extended to include a macroscopic gel which transitioned from a densely and covalently crosslinked network to one with larger distances between the covalent crosslinks when heated. These architectural transformations present an entirely new approach to 'smart' materials.

  3. Macromolecular metamorphosis via stimulus-induced transformations of polymer architecture

    Science.gov (United States)

    Sun, Hao; Kabb, Christopher P.; Dai, Yuqiong; Hill, Megan R.; Ghiviriga, Ion; Bapat, Abhijeet P.; Sumerlin, Brent S.

    2017-08-01

    Macromolecular architecture plays a pivotal role in determining the properties of polymers. When designing polymers for specific applications, it is not only the size of a macromolecule that must be considered, but also its shape. In most cases, the topology of a polymer is a static feature that is inalterable once synthesized. Using reversible-covalent chemistry to prompt the disconnection of chemical bonds and the formation of new linkages in situ, we report polymers that undergo dramatic topological transformations via a process we term macromolecular metamorphosis. Utilizing this technique, a linear amphiphilic block copolymer or hyperbranched polymer undergoes 'metamorphosis' into comb, star and hydrophobic block copolymer architectures. This approach was extended to include a macroscopic gel which transitioned from a densely and covalently crosslinked network to one with larger distances between the covalent crosslinks when heated. These architectural transformations present an entirely new approach to 'smart' materials.

  4. Impact of synchrotron radiation on macromolecular crystallography: a personal view

    Science.gov (United States)

    Dauter, Zbigniew; Jaskolski, Mariusz; Wlodawer, Alexander

    2010-01-01

    The introduction of synchrotron radiation sources almost four decades ago has led to a revolutionary change in the way that diffraction data from macromolecular crystals are being collected. Here a brief history of the development of methodologies that took advantage of the availability of synchrotron sources are presented, and some personal experiences with the utilization of synchrotrons in the early days are recalled. PMID:20567074

  5. Modeling the multi-scale mechanisms of macromolecular resource allocation

    DEFF Research Database (Denmark)

    Yang, Laurence; Yurkovich, James T; King, Zachary A

    2018-01-01

    As microbes face changing environments, they dynamically allocate macromolecular resources to produce a particular phenotypic state. Broad 'omics' data sets have revealed several interesting phenomena regarding how the proteome is allocated under differing conditions, but the functional consequen...... and detail how mathematical models have aided in our understanding of these processes. Ultimately, such modeling efforts have helped elucidate the principles of proteome allocation and hold promise for further discovery....

  6. Application of complex macromolecular architectures for advanced microelectronic materials.

    Science.gov (United States)

    Hedrick, James L; Magbitang, Teddie; Connor, Eric F; Glauser, Thierry; Volksen, Willi; Hawker, Craig J; Lee, Victor Y; Miller, Robert D

    2002-08-02

    The distinctive features of well-defined, three-dimensional macromolecules with topologies designed to enhance solubility and amplify end-group functionality facilitated nanophase morphologies in mixtures with organosilicates and ultimately nanoporous organosilicate networks. Novel macromolecular architectures including dendritic and star-shaped polymers and organic nanoparticles were prepared by a modular approach from several libraries of building blocks including various generations of dendritic initiators and dendrons, selectively placed to amplify functionality and/or arm number, coupled with living polymerization techniques. Mixtures of an organosilicate and the macromolecular template were deposited, cured, and the phase separation of the organic component, organized the vitrifying organosilicate into nanostructures. Removal of the sacrificial macromolecular template, also denoted as porogen, by thermolysis, yielded the desired nanoporous organosilicate, and the size scale of phase separation was strongly dependent on the chain topology. These materials were designed for use as interlayer, ultra-low dielectric insulators for on-chip applications with dielectric constant values as low as 1.5. The porogen design, chemistry and role of polymer architecture on hybrid and pore morphology will be emphasized.

  7. International summer school on macromolecular crystallographic computing. Final report

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1998-08-01

    The School was the seventh in a series of International Union of Crystallography (IUCr) Crystallographic Symposia. The format of the School was formal lectures in the morning, tutorials in the afternoon, and software demonstrations and more lectures in the evening. The full program which left both the organizers and attendees exhausted, reflects the current state of excitement in the field of macromolecular structure determination using the technique of X-ray crystallography. The new and improved technologies and techniques described in these Proceedings are contributing to that growth and at the same time, as pointed out in the paper given by Sussman, creating challenges for the Protein Data Bank (PDB). As the School progressed, the authors were struck by the similarities to events which took place in small molecule crystallography beginning some 20 to 25 years ago. Growth then was fueled by the advent of new algorithms, affordable computer hardware, and good software. So it is today for macromolecular crystallography, but with the added bonus of the Internet which is changing how scientist conduct their research. Flack presented this view as part of his on-going contribution to how crystallographers use the Internet. After presentations discussing structures en masse they returned to the more traditional mode of presentation which parallels the determination of a single macromolecular structure: data collection -- phasing -- model building and visualization -- refinement.

  8. Cryo-Electron Tomography for Structural Characterization of Macromolecular Complexes

    Science.gov (United States)

    Cope, Julia; Heumann, John; Hoenger, Andreas

    2011-01-01

    Cryo-electron tomography (cryo-ET) is an emerging 3-D reconstruction technology that combines the principles of tomographic 3-D reconstruction with the unmatched structural preservation of biological material embedded in vitreous ice. Cryo-ET is particularly suited to investigating cell-biological samples and large macromolecular structures that are too polymorphic to be reconstructed by classical averaging-based 3-D reconstruction procedures. This unit aims to make cryo-ET accessible to newcomers and discusses the specialized equipment required, as well as the relevant advantages and hurdles associated with sample preparation by vitrification and cryo-ET. Protocols describe specimen preparation, data recording and 3-D data reconstruction for cryo-ET, with a special focus on macromolecular complexes. A step-by-step procedure for specimen vitrification by plunge freezing is provided, followed by the general practicalities of tilt-series acquisition for cryo-ET, including advice on how to select an area appropriate for acquiring a tilt series. A brief introduction to the underlying computational reconstruction principles applied in tomography is described, along with instructions for reconstructing a tomogram from cryo-tilt series data. Finally, a method is detailed for extracting small subvolumes containing identical macromolecular structures from tomograms for alignment and averaging as a means to increase the signal-to-noise ratio and eliminate missing wedge effects inherent in tomographic reconstructions. PMID:21842467

  9. What Macromolecular Crowding Can Do to a Protein

    Science.gov (United States)

    Kuznetsova, Irina M.; Turoverov, Konstantin K.; Uversky, Vladimir N.

    2014-01-01

    The intracellular environment represents an extremely crowded milieu, with a limited amount of free water and an almost complete lack of unoccupied space. Obviously, slightly salted aqueous solutions containing low concentrations of a biomolecule of interest are too simplistic to mimic the “real life” situation, where the biomolecule of interest scrambles and wades through the tightly packed crowd. In laboratory practice, such macromolecular crowding is typically mimicked by concentrated solutions of various polymers that serve as model “crowding agents”. Studies under these conditions revealed that macromolecular crowding might affect protein structure, folding, shape, conformational stability, binding of small molecules, enzymatic activity, protein-protein interactions, protein-nucleic acid interactions, and pathological aggregation. The goal of this review is to systematically analyze currently available experimental data on the variety of effects of macromolecular crowding on a protein molecule. The review covers more than 320 papers and therefore represents one of the most comprehensive compendia of the current knowledge in this exciting area. PMID:25514413

  10. Spontaneous pneumothorax in weightlifters.

    Science.gov (United States)

    Marnejon, T; Sarac, S; Cropp, A J

    1995-06-01

    Spontaneous pneumothorax is infrequently caused by strenuous exertion. To our knowledge there has only been one case of spontaneous pneumothorax associated with weightlifting reported in the medical literature. We describe three consecutive cases of spontaneous pneumothorax associated with weightlifting. We postulate that spontaneous pneumothorax in these patients may be secondary to improper breathing techniques. It is important that physicians and weight trainers be aware of the association between weight lifting and spontaneous pneumothorax and assure that proper instruction is given to athletes who work with weights.

  11. Development of an online UV–visible microspectrophotometer for a macromolecular crystallography beamline

    Energy Technology Data Exchange (ETDEWEB)

    Shimizu, Nobutaka, E-mail: nobutaka.shimizu@kek.jp [SPring-8/JASRI, 1-1-1 Koto, Sayo-cho, Sayo-gun, Hyogo 679-5198 (Japan); High Energy Accelerator Research Organization (KEK), 1-1 Oho, Tsukuba, Ibaraki 305-0801 (Japan); Shimizu, Tetsuya [RIKEN SPring-8 Center, 1-1-1 Koto, Sayo-cho, Sayo-gun, Hyogo 679-5148 (Japan); Baba, Seiki; Hasegawa, Kazuya [SPring-8/JASRI, 1-1-1 Koto, Sayo-cho, Sayo-gun, Hyogo 679-5198 (Japan); Yamamoto, Masaki [RIKEN SPring-8 Center, 1-1-1 Koto, Sayo-cho, Sayo-gun, Hyogo 679-5148 (Japan); Kumasaka, Takashi [SPring-8/JASRI, 1-1-1 Koto, Sayo-cho, Sayo-gun, Hyogo 679-5198 (Japan)

    2013-11-01

    An online UV–visible microspectrophotometer has been developed for the macromolecular crystallography beamline at SPring-8. Details of this spectrophotometer are reported. Measurement of the UV–visible absorption spectrum is a convenient technique for detecting chemical changes of proteins, and it is therefore useful to combine spectroscopy and diffraction studies. An online microspectrophotometer for the UV–visible region was developed and installed on the macromolecular crystallography beamline, BL38B1, at SPring-8. This spectrophotometer is equipped with a difference dispersive double monochromator, a mercury–xenon lamp as the light source, and a photomultiplier as the detector. The optical path is mostly constructed using mirrors, in order to obtain high brightness in the UV region, and the confocal optics are assembled using a cross-slit diaphragm like an iris to eliminate stray light. This system can measure optical densities up to a maximum of 4.0. To study the effect of radiation damage, preliminary measurements of glucose isomerase and thaumatin crystals were conducted in the UV region. Spectral changes dependent on X-ray dose were observed at around 280 nm, suggesting that structural changes involving Trp or Tyr residues occurred in the protein crystal. In the case of the thaumatin crystal, a broad peak around 400 nm was also generated after X-ray irradiation, suggesting the cleavage of a disulfide bond. Dose-dependent spectral changes were also observed in cryo-solutions alone, and these changes differed with the composition of the cryo-solution. These responses in the UV region are informative regarding the state of the sample; consequently, this device might be useful for X-ray crystallography.

  12. Controlling macromolecular topology with genetically encoded SpyTag-SpyCatcher chemistry.

    Science.gov (United States)

    Zhang, Wen-Bin; Sun, Fei; Tirrell, David A; Arnold, Frances H

    2013-09-18

    Control of molecular topology constitutes a fundamental challenge in macromolecular chemistry. Here we describe the synthesis and characterization of artificial elastin-like proteins (ELPs) with unconventional nonlinear topologies including circular, tadpole, star, and H-shaped proteins using genetically encoded SpyTag-SpyCatcher chemistry. SpyTag is a short polypeptide that binds its protein partner SpyCatcher and forms isopeptide bonds under physiological conditions. Sequences encoding SpyTag and SpyCatcher can be strategically placed into ELP genes to direct post-translational topological modification in situ. Placement of SpyTag at the N-terminus and SpyCatcher at the C-terminus directs formation of circular ELPs. Induction of expression at 16 °C with 10 μM IPTG yields 80% monomeric cyclic protein. When SpyTag is placed in the middle of the chain, it exhibits an even stronger tendency toward cyclization, yielding up to 94% monomeric tadpole proteins. Telechelic ELPs containing either SpyTag or SpyCatcher can be expressed, purified, and then coupled spontaneously upon mixing in vitro. Block proteins, 3-arm or 4-arm star proteins, and H-shaped proteins have been prepared, with the folded CnaB2 domain that results from the SpyTag-SpyCatcher reaction as the molecular core or branch junction. The modular character of the SpyTag-SpyCatcher strategy should make it useful for preparing nonlinear macromolecules of diverse sequence and structure.

  13. Repair of radiation damage in mammalian cells

    International Nuclear Information System (INIS)

    Setlow, R.B.

    1981-01-01

    The responses, such as survival, mutation, and carcinogenesis, of mammalian cells and tissues to radiation are dependent not only on the magnitude of the damage to macromolecular structures - DNA, RNA, protein, and membranes - but on the rates of macromolecular syntheses of cells relative to the half-lives of the damages. Cells possess a number of mechanisms for repairing damage to DNA. If the repair systems are rapid and error free, cells can tolerate much larger doses than if repair is slow or error prone. It is important to understand the effects of radiation and the repair of radiation damage because there exist reasonable amounts of epidemiological data that permits the construction of dose-response curves for humans. The shapes of such curves or the magnitude of the response will depend on repair. Radiation damage is emphasized because: (a) radiation dosimetry, with all its uncertainties for populations, is excellent compared to chemical dosimetry; (b) a number of cancer-prone diseases are known in which there are defects in DNA repair and radiation results in more chromosomal damage in cells from such individuals than in cells from normal individuals; (c) in some cases, specific radiation products in DNA have been correlated with biological effects, and (d) many chemical effects seem to mimic radiation effects. A further reason for emphasizing damage to DNA is the wealth of experimental evidence indicating that damages to DNA can be initiating events in carcinogenesis

  14. The contrasting effect of macromolecular crowding on amyloid fibril formation.

    Directory of Open Access Journals (Sweden)

    Qian Ma

    Full Text Available Amyloid fibrils associated with neurodegenerative diseases can be considered biologically relevant failures of cellular quality control mechanisms. It is known that in vivo human Tau protein, human prion protein, and human copper, zinc superoxide dismutase (SOD1 have the tendency to form fibril deposits in a variety of tissues and they are associated with different neurodegenerative diseases, while rabbit prion protein and hen egg white lysozyme do not readily form fibrils and are unlikely to cause neurodegenerative diseases. In this study, we have investigated the contrasting effect of macromolecular crowding on fibril formation of different proteins.As revealed by assays based on thioflavin T binding and turbidity, human Tau fragments, when phosphorylated by glycogen synthase kinase-3β, do not form filaments in the absence of a crowding agent but do form fibrils in the presence of a crowding agent, and the presence of a strong crowding agent dramatically promotes amyloid fibril formation of human prion protein and its two pathogenic mutants E196K and D178N. Such an enhancing effect of macromolecular crowding on fibril formation is also observed for a pathological human SOD1 mutant A4V. On the other hand, rabbit prion protein and hen lysozyme do not form amyloid fibrils when a crowding agent at 300 g/l is used but do form fibrils in the absence of a crowding agent. Furthermore, aggregation of these two proteins is remarkably inhibited by Ficoll 70 and dextran 70 at 200 g/l.We suggest that proteins associated with neurodegenerative diseases are more likely to form amyloid fibrils under crowded conditions than in dilute solutions. By contrast, some of the proteins that are not neurodegenerative disease-associated are unlikely to misfold in crowded physiological environments. A possible explanation for the contrasting effect of macromolecular crowding on these two sets of proteins (amyloidogenic proteins and non-amyloidogenic proteins has been

  15. Thermodynamic signatures in macromolecular interactions involving conformational flexibility.

    Science.gov (United States)

    Menzel, Anja; Neumann, Piotr; Schwieger, Christian; Stubbs, Milton T

    2014-07-01

    The energetics of macromolecular interactions are complex, particularly where protein flexibility is involved. Exploiting serendipitous differences in the plasticity of a series of closely related trypsin variants, we analyzed the enthalpic and entropic contributions accompanying interaction with L45K-eglin C. Binding of the four variants show significant differences in released heat, although the affinities vary little, in accordance with the principle of enthalpy-entropy compensation. Binding of the most disordered variant is almost entirely enthalpically driven, with practically no entropy change. As structures of the complexes reveal negligible differences in protein-inhibitor contacts, we conclude that solvent effects contribute significantly to binding affinities.

  16. Structural analysis of nanoparticulate carriers for encapsulation of macromolecular drugs

    Czech Academy of Sciences Publication Activity Database

    Angelov, Borislav; Garamus, V.M.; Drechsler, M.; Angelova, A.

    2017-01-01

    Roč. 235, Jun (2017), s. 83-89 ISSN 0167-7322 R&D Projects: GA MŠk EF15_003/0000447; GA MŠk EF15_008/0000162 Grant - others:OP VVV - ELIBIO(XE) CZ.02.1.01/0.0/0.0/15_003/0000447; ELI Beamlines(XE) CZ.02.1.01/0.0/0.0/15_008/0000162 Institutional support: RVO:68378271 Keywords : self-assembled nanocarriers * liquid crystalline phase transitions * cationic lipids * macromolecular drugs Subject RIV: BO - Biophysics OBOR OECD: Biophysics Impact factor: 3.648, year: 2016

  17. Workshop on algorithms for macromolecular modeling. Final project report, June 1, 1994--May 31, 1995

    Energy Technology Data Exchange (ETDEWEB)

    Leimkuhler, B.; Hermans, J.; Skeel, R.D.

    1995-07-01

    A workshop was held on algorithms and parallel implementations for macromolecular dynamics, protein folding, and structural refinement. This document contains abstracts and brief reports from that workshop.

  18. PRIGo: a new multi-axis goniometer for macromolecular crystallography

    Energy Technology Data Exchange (ETDEWEB)

    Waltersperger, Sandro; Olieric, Vincent, E-mail: vincent.olieric@psi.ch; Pradervand, Claude [Paul Scherrer Institute, Villigen PSI (Switzerland); Glettig, Wayne [Centre Suisse d’Electronique et Microtechnique SA, Neuchâtel 2002 (Switzerland); Salathe, Marco; Fuchs, Martin R.; Curtin, Adrian; Wang, Xiaoqiang; Ebner, Simon; Panepucci, Ezequiel; Weinert, Tobias [Paul Scherrer Institute, Villigen PSI (Switzerland); Schulze-Briese, Clemens [Dectris Ltd, Baden 5400 (Switzerland); Wang, Meitian, E-mail: vincent.olieric@psi.ch [Paul Scherrer Institute, Villigen PSI (Switzerland)

    2015-05-09

    The design and performance of the new multi-axis goniometer PRIGo developed at the Swiss Light Source at Paul Scherrer Institute is described. The Parallel Robotics Inspired Goniometer (PRIGo) is a novel compact and high-precision goniometer providing an alternative to (mini-)kappa, traditional three-circle goniometers and Eulerian cradles used for sample reorientation in macromolecular crystallography. Based on a combination of serial and parallel kinematics, PRIGo emulates an arc. It is mounted on an air-bearing stage for rotation around ω and consists of four linear positioners working synchronously to achieve x, y, z translations and χ rotation (0–90°), followed by a ϕ stage (0–360°) for rotation around the sample holder axis. Owing to the use of piezo linear positioners and active correction, PRIGo features spheres of confusion of <1 µm, <7 µm and <10 µm for ω, χ and ϕ, respectively, and is therefore very well suited for micro-crystallography. PRIGo enables optimal strategies for both native and experimental phasing crystallographic data collection. Herein, PRIGo hardware and software, its calibration, as well as applications in macromolecular crystallography are described.

  19. Outrunning free radicals in room-temperature macromolecular crystallography

    International Nuclear Information System (INIS)

    Owen, Robin L.; Axford, Danny; Nettleship, Joanne E.; Owens, Raymond J.; Robinson, James I.; Morgan, Ann W.; Doré, Andrew S.; Lebon, Guillaume; Tate, Christopher G.; Fry, Elizabeth E.; Ren, Jingshan; Stuart, David I.; Evans, Gwyndaf

    2012-01-01

    A systematic increase in lifetime is observed in room-temperature protein and virus crystals through the use of reduced exposure times and a fast detector. A significant increase in the lifetime of room-temperature macromolecular crystals is reported through the use of a high-brilliance X-ray beam, reduced exposure times and a fast-readout detector. This is attributed to the ability to collect diffraction data before hydroxyl radicals can propagate through the crystal, fatally disrupting the lattice. Hydroxyl radicals are shown to be trapped in amorphous solutions at 100 K. The trend in crystal lifetime was observed in crystals of a soluble protein (immunoglobulin γ Fc receptor IIIa), a virus (bovine enterovirus serotype 2) and a membrane protein (human A 2A adenosine G-protein coupled receptor). The observation of a similar effect in all three systems provides clear evidence for a common optimal strategy for room-temperature data collection and will inform the design of future synchrotron beamlines and detectors for macromolecular crystallography

  20. Outrunning free radicals in room-temperature macromolecular crystallography

    Energy Technology Data Exchange (ETDEWEB)

    Owen, Robin L., E-mail: robin.owen@diamond.ac.uk; Axford, Danny [Diamond Light Source, Harwell Science and Innovation Campus, Didcot OX11 0DE (United Kingdom); Nettleship, Joanne E.; Owens, Raymond J. [Rutherford Appleton Laboratory, Didcot OX11 0FA (United Kingdom); The Henry Wellcome Building for Genomic Medicine, Roosevelt Drive, Oxford OX3 7BN (United Kingdom); Robinson, James I.; Morgan, Ann W. [University of Leeds, Leeds LS9 7FT (United Kingdom); Doré, Andrew S. [Heptares Therapeutics Ltd, BioPark, Welwyn Garden City AL7 3AX (United Kingdom); Lebon, Guillaume; Tate, Christopher G. [MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH (United Kingdom); Fry, Elizabeth E.; Ren, Jingshan [The Henry Wellcome Building for Genomic Medicine, Roosevelt Drive, Oxford OX3 7BN (United Kingdom); Stuart, David I. [Diamond Light Source, Harwell Science and Innovation Campus, Didcot OX11 0DE (United Kingdom); The Henry Wellcome Building for Genomic Medicine, Roosevelt Drive, Oxford OX3 7BN (United Kingdom); Evans, Gwyndaf [Diamond Light Source, Harwell Science and Innovation Campus, Didcot OX11 0DE (United Kingdom)

    2012-06-15

    A systematic increase in lifetime is observed in room-temperature protein and virus crystals through the use of reduced exposure times and a fast detector. A significant increase in the lifetime of room-temperature macromolecular crystals is reported through the use of a high-brilliance X-ray beam, reduced exposure times and a fast-readout detector. This is attributed to the ability to collect diffraction data before hydroxyl radicals can propagate through the crystal, fatally disrupting the lattice. Hydroxyl radicals are shown to be trapped in amorphous solutions at 100 K. The trend in crystal lifetime was observed in crystals of a soluble protein (immunoglobulin γ Fc receptor IIIa), a virus (bovine enterovirus serotype 2) and a membrane protein (human A{sub 2A} adenosine G-protein coupled receptor). The observation of a similar effect in all three systems provides clear evidence for a common optimal strategy for room-temperature data collection and will inform the design of future synchrotron beamlines and detectors for macromolecular crystallography.

  1. Dendrimer-based Macromolecular MRI Contrast Agents: Characteristics and Application

    Directory of Open Access Journals (Sweden)

    Hisataka Kobayashi

    2003-01-01

    Full Text Available Numerous macromolecular MRI contrast agents prepared employing relatively simple chemistry may be readily available that can provide sufficient enhancement for multiple applications. These agents operate using a ~100-fold lower concentration of gadolinium ions in comparison to the necessary concentration of iodine employed in CT imaging. Herein, we describe some of the general potential directions of macromolecular MRI contrast agents using our recently reported families of dendrimer-based agents as examples. Changes in molecular size altered the route of excretion. Smaller-sized contrast agents less than 60 kDa molecular weight were excreted through the kidney resulting in these agents being potentially suitable as functional renal contrast agents. Hydrophilic and larger-sized contrast agents were found better suited for use as blood pool contrast agents. Hydrophobic variants formed with polypropylenimine diaminobutane dendrimer cores created liver contrast agents. Larger hydrophilic agents are useful for lymphatic imaging. Finally, contrast agents conjugated with either monoclonal antibodies or with avidin are able to function as tumor-specific contrast agents, which also might be employed as therapeutic drugs for either gadolinium neutron capture therapy or in conjunction with radioimmunotherapy.

  2. Branched Macromolecular Architectures for Degradable, Multifunctional Phosphorus-Based Polymers.

    Science.gov (United States)

    Henke, Helena; Brüggemann, Oliver; Teasdale, Ian

    2017-02-01

    This feature article briefly highlights some of the recent advances in polymers in which phosphorus is an integral part of the backbone, with a focus on the preparation of functional, highly branched, soluble polymers. A comparison is made between the related families of materials polyphosphazenes, phosphazene/phosphorus-based dendrimers and polyphosphoesters. The work described herein shows this to be a rich and burgeoning field, rapidly catching up with organic chemistry in terms of the macromolecular synthetic control and variety of available macromolecular architectures, whilst offering unique property combinations not available with carbon backbones, such as tunable degradation rates, high multi-valency and facile post-polymerization functionalization. As an example of their use in advanced applications, we highlight some investigations into their use as water-soluble drug carriers, whereby in particular the degradability in combination with multivalent nature has made them useful materials, as underlined by some of the recent studies in this area. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Data Management System at the Photon Factory Macromolecular Crystallography Beamline

    International Nuclear Information System (INIS)

    Yamada, Y; Matsugaki, N; Chavas, L M G; Hiraki, M; Igarashi, N; Wakatsuki, S

    2013-01-01

    Macromolecular crystallography is a very powerful tool to investigate three-dimensional structures of macromolecules at the atomic level, and is widely spread among structural biology researchers. Due to recent upgrades of the macromolecular crystallography beamlines at the Photon Factory, beamline throughput has improved, allowing more experiments to be conducted during a user's beam time. Although the number of beamlines has increased, so has the number of beam time applications. Consequently, both the experimental data from users' experiments and data derived from beamline operations have dramatically increased, causing difficulties in organizing these diverse and large amounts of data for the beamline operation staff and users. To overcome this problem, we have developed a data management system by introducing commercial middleware, which consists of a controller, database, and web servers. We have prepared several database projects using this system. Each project is dedicated to a certain aspect such as experimental results, beam time applications, beam time schedule, or beamline operation reports. Then we designed a scheme to link all the database projects.

  4. Variable effects of soman on macromolecular secretion by ferret trachea

    Energy Technology Data Exchange (ETDEWEB)

    McBride, R.K.; Zwierzynski, D.J.; Stone, K.K.; Culp, D.J.; Marin, M.G. (Univ. of Rochester School of Medicine and Dentistry, NY (USA))

    1991-01-01

    The purpose of this study was to examine the effect of the anticholinesterase agent, soman, on macromolecular secretion by ferret trachea, in vitro. We mounted pieces of ferret trachea in Ussing-type chambers. Secreted sulfated macromolecules were radiolabeled by adding 500 microCi of {sup 35}SO{sub 4} to the submucosal medium and incubating for 17 hr. Soman added to the submucosal side produced a concentration-dependent increase in radiolabeled macromolecular release with a maximal secretory response (mean +/- SD) of 202 +/- 125% (n = 8) relative to the basal secretion rate at a concentration of 10{sup {minus} 7} M. The addition of either 10{sup {minus}6} M pralidoxime (acetylcholinesterase reactivator) or 10{sup {minus}6} M atropine blocked the response to 10{sup {minus}7} M soman. At soman concentrations greater than 10{sup {minus}7} M, secretion rate decreased and was not significantly different from basal secretion. Additional experiments utilizing acetylcholine and the acetylcholinesterase inhibitor, physostigmine, suggest that inhibition of secretion by high concentrations of soman may be due to a secondary antagonistic effect of soman on muscarinic receptors.

  5. Enzymes as Green Catalysts for Precision Macromolecular Synthesis.

    Science.gov (United States)

    Shoda, Shin-ichiro; Uyama, Hiroshi; Kadokawa, Jun-ichi; Kimura, Shunsaku; Kobayashi, Shiro

    2016-02-24

    The present article comprehensively reviews the macromolecular synthesis using enzymes as catalysts. Among the six main classes of enzymes, the three classes, oxidoreductases, transferases, and hydrolases, have been employed as catalysts for the in vitro macromolecular synthesis and modification reactions. Appropriate design of reaction including monomer and enzyme catalyst produces macromolecules with precisely controlled structure, similarly as in vivo enzymatic reactions. The reaction controls the product structure with respect to substrate selectivity, chemo-selectivity, regio-selectivity, stereoselectivity, and choro-selectivity. Oxidoreductases catalyze various oxidation polymerizations of aromatic compounds as well as vinyl polymerizations. Transferases are effective catalysts for producing polysaccharide having a variety of structure and polyesters. Hydrolases catalyzing the bond-cleaving of macromolecules in vivo, catalyze the reverse reaction for bond forming in vitro to give various polysaccharides and functionalized polyesters. The enzymatic polymerizations allowed the first in vitro synthesis of natural polysaccharides having complicated structures like cellulose, amylose, xylan, chitin, hyaluronan, and chondroitin. These polymerizations are "green" with several respects; nontoxicity of enzyme, high catalyst efficiency, selective reactions under mild conditions using green solvents and renewable starting materials, and producing minimal byproducts. Thus, the enzymatic polymerization is desirable for the environment and contributes to "green polymer chemistry" for maintaining sustainable society.

  6. Changes in the macromolecular structure of coals with pyrolysis temperature

    Energy Technology Data Exchange (ETDEWEB)

    Ndaji, F.E.; Butterfield, I.M.; Thomas, K.M. [University of Newcastle upon Tyne, Newcastle upon Tyne (United Kingdom). Northern Carbon Research Labs., Dept. of Chemistry

    1997-01-01

    The macromolecular structure of coal is characterised by its cross-link density. This paper describes a study of the effect of pyrolysis temperature on the macromolecular structure of coal using solvent swelling techniques. Heat treatment initially dissociates the intermolecular interactions in the coal and cleaves some cross-links, leading to increase in the solvent swelling of the coal, which indicates a decrease in the cross-link density. The solvent swelling reaches a maximum before cross-linking reactions predominate, causing a progressive increase in cross-link density and a decrease in solvent swelling. For lower-rank coals there appears to be an overlap (near the temperature of minimum cross-link density) of the dissociation of intermolecular interactions and thermal decomposition. Appreciable decrease in the apparent cross-link density of high-rank coals as indicated by increase in solvent swelling was observed only after thermal decomposition had commenced. Major decomposition involves cross-linking reactions leading to the formation of chars. However, the solvent swelling characteristics continue to change above the resolidification temperature, eventually ceasing at {approximately}600{degree}C. The results are discussed in relation to measurements of thermoplastic properties and devolatilization characteristics. 23 refs., 4 figs., 3 tabs.

  7. The Phenix software for automated determination of macromolecular structures.

    Science.gov (United States)

    Adams, Paul D; Afonine, Pavel V; Bunkóczi, Gábor; Chen, Vincent B; Echols, Nathaniel; Headd, Jeffrey J; Hung, Li-Wei; Jain, Swati; Kapral, Gary J; Grosse Kunstleve, Ralf W; McCoy, Airlie J; Moriarty, Nigel W; Oeffner, Robert D; Read, Randy J; Richardson, David C; Richardson, Jane S; Terwilliger, Thomas C; Zwart, Peter H

    2011-09-01

    X-ray crystallography is a critical tool in the study of biological systems. It is able to provide information that has been a prerequisite to understanding the fundamentals of life. It is also a method that is central to the development of new therapeutics for human disease. Significant time and effort are required to determine and optimize many macromolecular structures because of the need for manual interpretation of complex numerical data, often using many different software packages, and the repeated use of interactive three-dimensional graphics. The Phenix software package has been developed to provide a comprehensive system for macromolecular crystallographic structure solution with an emphasis on automation. This has required the development of new algorithms that minimize or eliminate subjective input in favor of built-in expert-systems knowledge, the automation of procedures that are traditionally performed by hand, and the development of a computational framework that allows a tight integration between the algorithms. The application of automated methods is particularly appropriate in the field of structural proteomics, where high throughput is desired. Features in Phenix for the automation of experimental phasing with subsequent model building, molecular replacement, structure refinement and validation are described and examples given of running Phenix from both the command line and graphical user interface. Copyright © 2011 Elsevier Inc. All rights reserved.

  8. Variable effects of soman on macromolecular secretion by ferret trachea

    International Nuclear Information System (INIS)

    McBride, R.K.; Zwierzynski, D.J.; Stone, K.K.; Culp, D.J.; Marin, M.G.

    1991-01-01

    The purpose of this study was to examine the effect of the anticholinesterase agent, soman, on macromolecular secretion by ferret trachea, in vitro. We mounted pieces of ferret trachea in Ussing-type chambers. Secreted sulfated macromolecules were radiolabeled by adding 500 microCi of 35 SO 4 to the submucosal medium and incubating for 17 hr. Soman added to the submucosal side produced a concentration-dependent increase in radiolabeled macromolecular release with a maximal secretory response (mean +/- SD) of 202 +/- 125% (n = 8) relative to the basal secretion rate at a concentration of 10 - 7 M. The addition of either 10 -6 M pralidoxime (acetylcholinesterase reactivator) or 10 -6 M atropine blocked the response to 10 -7 M soman. At soman concentrations greater than 10 -7 M, secretion rate decreased and was not significantly different from basal secretion. Additional experiments utilizing acetylcholine and the acetylcholinesterase inhibitor, physostigmine, suggest that inhibition of secretion by high concentrations of soman may be due to a secondary antagonistic effect of soman on muscarinic receptors

  9. PRIGo: a new multi-axis goniometer for macromolecular crystallography.

    Science.gov (United States)

    Waltersperger, Sandro; Olieric, Vincent; Pradervand, Claude; Glettig, Wayne; Salathe, Marco; Fuchs, Martin R; Curtin, Adrian; Wang, Xiaoqiang; Ebner, Simon; Panepucci, Ezequiel; Weinert, Tobias; Schulze-Briese, Clemens; Wang, Meitian

    2015-07-01

    The Parallel Robotics Inspired Goniometer (PRIGo) is a novel compact and high-precision goniometer providing an alternative to (mini-)kappa, traditional three-circle goniometers and Eulerian cradles used for sample reorientation in macromolecular crystallography. Based on a combination of serial and parallel kinematics, PRIGo emulates an arc. It is mounted on an air-bearing stage for rotation around ω and consists of four linear positioners working synchronously to achieve x, y, z translations and χ rotation (0-90°), followed by a ϕ stage (0-360°) for rotation around the sample holder axis. Owing to the use of piezo linear positioners and active correction, PRIGo features spheres of confusion of <1 µm, <7 µm and <10 µm for ω, χ and ϕ, respectively, and is therefore very well suited for micro-crystallography. PRIGo enables optimal strategies for both native and experimental phasing crystallographic data collection. Herein, PRIGo hardware and software, its calibration, as well as applications in macromolecular crystallography are described.

  10. Spontaneous uterine rupture

    African Journals Online (AJOL)

    ABSTRACT. Rupture of a gravid uterus is a surgical emergency. Predisposing factors include a scarred uterus. Spontaneous rupture of an unscarred uterus during pregnancy is a rare occurrence. We hereby present the case of a spontaneous complete uterine rupture at a gestational age of 34 weeks in a 35 year old patient ...

  11. Spontaneous intracranial hypotension.

    LENUS (Irish Health Repository)

    Fullam, L

    2012-01-31

    INTRODUCTION: Spontaneous\\/primary intracranial hypotension is characterised by orthostatic headache and is associated with characteristic magnetic resonance imaging findings. CASE REPORT: We present a case report of a patient with typical symptoms and classical radiological images. DISCUSSION: Spontaneous intracranial hypotension is an under-recognised cause of headache and can be diagnosed by history of typical orthostatic headache and findings on MRI brain.

  12. Associative Pattern Recognition Through Macro-molecular Self-Assembly

    Science.gov (United States)

    Zhong, Weishun; Schwab, David J.; Murugan, Arvind

    2017-05-01

    We show that macro-molecular self-assembly can recognize and classify high-dimensional patterns in the concentrations of N distinct molecular species. Similar to associative neural networks, the recognition here leverages dynamical attractors to recognize and reconstruct partially corrupted patterns. Traditional parameters of pattern recognition theory, such as sparsity, fidelity, and capacity are related to physical parameters, such as nucleation barriers, interaction range, and non-equilibrium assembly forces. Notably, we find that self-assembly bears greater similarity to continuous attractor neural networks, such as place cell networks that store spatial memories, rather than discrete memory networks. This relationship suggests that features and trade-offs seen here are not tied to details of self-assembly or neural network models but are instead intrinsic to associative pattern recognition carried out through short-ranged interactions.

  13. NATO Advanced Study Institute on Evolving Methods for Macromolecular Gystallography

    CERN Document Server

    Read, Randy J

    2007-01-01

    X-ray crystallography is the pre-eminent technique for visualizing the structures of macromolecules at atomic resolution. These structures are central to understanding the detailed mechanisms of biological processes, and to discovering novel therapeutics using a structure-based approach. As yet, structures are known for only a small fraction of the proteins encoded by human and pathogenic genomes. To counter the myriad modern threats of disease, there is an urgent need to determine the structures of the thousands of proteins whose structure and function remain unknown. This volume draws on the expertise of leaders in the field of macromolecular crystallography to illuminate the dramatic developments that are accelerating progress in structural biology. Their contributions span the range of techniques from crystallization through data collection, structure solution and analysis, and show how modern high-throughput methods are contributing to a deeper understanding of medical problems.

  14. In-vacuum long-wavelength macromolecular crystallography.

    Science.gov (United States)

    Wagner, Armin; Duman, Ramona; Henderson, Keith; Mykhaylyk, Vitaliy

    2016-03-01

    Structure solution based on the weak anomalous signal from native (protein and DNA) crystals is increasingly being attempted as part of synchrotron experiments. Maximizing the measurable anomalous signal by collecting diffraction data at longer wavelengths presents a series of technical challenges caused by the increased absorption of X-rays and larger diffraction angles. A new beamline at Diamond Light Source has been built specifically for collecting data at wavelengths beyond the capability of other synchrotron macromolecular crystallography beamlines. Here, the theoretical considerations in support of the long-wavelength beamline are outlined and the in-vacuum design of the endstation is discussed, as well as other hardware features aimed at enhancing the accuracy of the diffraction data. The first commissioning results, representing the first in-vacuum protein structure solution, demonstrate the promising potential of the beamline.

  15. Comparative and evolutionary aspects of macromolecular translocation across membranes.

    Science.gov (United States)

    Tartakoff, Alan M; Tao, Tao

    2010-02-01

    Membrane barriers preserve the integrity of organelles of eukaryotic cells, yet the genesis and ongoing functions of the same organelles requires that their limiting membranes allow import and export of selected macromolecules. Multiple distinct mechanisms are used for this purpose, only some of which have been traced to prokaryotes. Some can accommodate both monomeric and also large heterooligomeric cargoes. The best characterized of these is nucleocytoplasmic transport. This synthesis compares the unidirectional and bidirectional mechanisms of macromolecular transport of the endoplasmic reticulum, mitochondria, peroxisomes and the nucleus, calls attention to the powerful experimental approaches which have been used for their elucidation, discusses their regulation and evolutionary origins, and highlights relatively unexplored areas. Copyright (c) 2009 Elsevier Ltd. All rights reserved.

  16. Large-volume protein crystal growth for neutron macromolecular crystallography.

    Science.gov (United States)

    Ng, Joseph D; Baird, James K; Coates, Leighton; Garcia-Ruiz, Juan M; Hodge, Teresa A; Huang, Sijay

    2015-04-01

    Neutron macromolecular crystallography (NMC) is the prevailing method for the accurate determination of the positions of H atoms in macromolecules. As neutron sources are becoming more available to general users, finding means to optimize the growth of protein crystals to sizes suitable for NMC is extremely important. Historically, much has been learned about growing crystals for X-ray diffraction. However, owing to new-generation synchrotron X-ray facilities and sensitive detectors, protein crystal sizes as small as in the nano-range have become adequate for structure determination, lessening the necessity to grow large crystals. Here, some of the approaches, techniques and considerations for the growth of crystals to significant dimensions that are now relevant to NMC are revisited. These include experimental strategies utilizing solubility diagrams, ripening effects, classical crystallization techniques, microgravity and theoretical considerations.

  17. Designing a synchrotron micro-focusing beamline for macromolecular crystallography.

    Science.gov (United States)

    Grochulski, Paweł; Cygler, Mirosław; Yates, Brian

    After a successful 10 years of operation, the Canadian Macromolecular Crystallography Facility 08ID-1 beamline will undergo an upgrade to establish micro-beam capability. This paper is mostly focussed on optics and computer simulations for ray tracing of the beamline. After completion, the focussed beam at the sample will have a much smaller size of 50 × 5 µm 2 (H x V), allowing measurement of X-ray diffraction patterns from much smaller crystals than possible presently. The beamline will be equipped with a fast sample changer and an ultra-low noise photon counting detector, allowing shutter-less operation of the beamline. Additionally, it will be possible to perform in-situ room-temperature experiments.

  18. The monitoring system for macromolecular crystallography beamlines at BSRF

    International Nuclear Information System (INIS)

    Guo Xian; Chang Guangcai; Gan Quan; Shi Hong; Liu Peng; Sun Gongxing

    2012-01-01

    The monitoring system for macromolecular crystallography beamlines at BSRF (Beijing Synchrotron Radiation Facility) based on LabVIEW is introduced. In order to guarantee a safe, stable, and reliable running for the beamline devices, the system monitors the state of vacuum, cooling-water, optical components, beam, Liquid nitrogen in the beamlines in real time, detects faults and gives the alarm timely. System underlying uses the driver developed for the field devices for data acquisition, Data of collection is uploaded to the data-sharing platform makes it accessible via a network share. The upper system divides modules according to the actual function, and establishes the main interface of the monitoring system of beamline. To Facilitate data storage, management and inquiry, the system use LabSQL toolkit to achieve the interconnection with MySQL database which data of collection is sent to. (authors)

  19. Macromolecular and dendrimer-based magnetic resonance contrast agents

    Energy Technology Data Exchange (ETDEWEB)

    Bumb, Ambika; Brechbiel, Martin W. (Radiation Oncology Branch, National Cancer Inst., National Inst. of Health, Bethesda, MD (United States)), e-mail: pchoyke@mail.nih.gov; Choyke, Peter (Molecular Imaging Program, National Cancer Inst., National Inst. of Health, Bethesda, MD (United States))

    2010-09-15

    Magnetic resonance imaging (MRI) is a powerful imaging modality that can provide an assessment of function or molecular expression in tandem with anatomic detail. Over the last 20-25 years, a number of gadolinium-based MR contrast agents have been developed to enhance signal by altering proton relaxation properties. This review explores a range of these agents from small molecule chelates, such as Gd-DTPA and Gd-DOTA, to macromolecular structures composed of albumin, polylysine, polysaccharides (dextran, inulin, starch), poly(ethylene glycol), copolymers of cystamine and cystine with GD-DTPA, and various dendritic structures based on polyamidoamine and polylysine (Gadomers). The synthesis, structure, biodistribution, and targeting of dendrimer-based MR contrast agents are also discussed

  20. Single-particle cryo-electron microscopy of macromolecular complexes.

    Science.gov (United States)

    Skiniotis, Georgios; Southworth, Daniel R

    2016-02-01

    Recent technological breakthroughs in image acquisition have enabled single-particle cryo-electron microscopy (cryo-EM) to achieve near-atomic resolution structural information for biological complexes. The improvements in image quality coupled with powerful computational methods for sorting distinct particle populations now also allow the determination of compositional and conformational ensembles, thereby providing key insights into macromolecular function. However, the inherent instability and dynamic nature of biological assemblies remain a tremendous challenge that often requires tailored approaches for successful implementation of the methodology. Here, we briefly describe the fundamentals of single-particle cryo-EM with an emphasis on covering the breadth of techniques and approaches, including low- and high-resolution methods, aiming to illustrate specific steps that are crucial for obtaining structural information by this method. © The Author 2015. Published by Oxford University Press on behalf of The Japanese Society of Microscopy. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  1. Balanced macromolecular biosynthesis in "protoplasts" of Streptococcus faecalis.

    Science.gov (United States)

    Roth, G S; Shockman, G D; Daneo-Moore, L

    1971-03-01

    Osmotically fragile forms of Streptococcus faecalis 9790 were grown in 0.5 m sucrose- or 0.5 m NH(4)Cl-stabilized medium. The "protoplast" cultures exhibit an average growth rate constant of 0.66 to 0.94 mass doublings/hr. In a variety of experiments, turbidity and the net content of protein, ribonucleic acid (RNA) and deoxyribonucleic acid increase at the same rate, indicating balanced macromolecular biosynthesis. A total of two to three mass doublings was obtained, with no evidence of cell division. After osmotic shock, "protoplast" cultures released 93 to 94% of their RNA content in a form not sedimentable at 12,800 x g for 15 min, in contrast to streptococci, which released 7% of their RNA content after the same treatment.

  2. 129 Xe NMR Relaxation-Based Macromolecular Sensing

    Energy Technology Data Exchange (ETDEWEB)

    Gomes, Muller D. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Materials Sciences Division; Univ. of California, Berkeley, CA (United States). Dept. of Chemistry; Dao, Phuong [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Materials Sciences Division; Univ. of California, Berkeley, CA (United States). Dept. of Chemistry; Jeong, Keunhong [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Materials Sciences Division; Univ. of California, Berkeley, CA (United States). Dept. of Chemistry; Slack, Clancy C. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Materials Sciences Division; Univ. of California, Berkeley, CA (United States). Dept. of Chemistry; Vassiliou, Christophoros C. [Univ. of California, Berkeley, CA (United States). Dept. of Chemistry; Finbloom, Joel A. [Univ. of California, Berkeley, CA (United States). Dept. of Chemistry; Francis, Matthew B. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Materials Sciences Division; Univ. of California, Berkeley, CA (United States). Dept. of Chemistry; Wemmer, David E. [Univ. of California, Berkeley, CA (United States). Dept. of Chemistry; Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Physical Biosciences Division; Pines, Alexander [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Materials Sciences Division; Univ. of California, Berkeley, CA (United States). Dept. of Chemistry

    2016-07-29

    A 129Xe NMR relaxation-based sensing approach is reported on that exploits changes in the bulk xenon relaxation rate induced by slowed tumbling of a cryptophane-based sensor upon target binding. The amplification afforded by detection of the bulk dissolved xenon allows sensitive detection of targets. The sensor comprises a xenon-binding cryptophane cage, a target interaction element, and a metal chelating agent. Xenon associated with the target-bound cryptophane cage is rapidly relaxed and then detected after exchange with the bulk. Here we show that large macromolecular targets increase the rotational correlation time of xenon, increasing its relaxation rate. Upon binding of a biotin-containing sensor to avidin at 1.5 μM concentration, the free xenon T2 is reduced by a factor of 4.

  3. E-MSD: the European Bioinformatics Institute Macromolecular Structure Database.

    Science.gov (United States)

    Boutselakis, H; Dimitropoulos, D; Fillon, J; Golovin, A; Henrick, K; Hussain, A; Ionides, J; John, M; Keller, P A; Krissinel, E; McNeil, P; Naim, A; Newman, R; Oldfield, T; Pineda, J; Rachedi, A; Copeland, J; Sitnov, A; Sobhany, S; Suarez-Uruena, A; Swaminathan, J; Tagari, M; Tate, J; Tromm, S; Velankar, S; Vranken, W

    2003-01-01

    The E-MSD macromolecular structure relational database (http://www.ebi.ac.uk/msd) is designed to be a single access point for protein and nucleic acid structures and related information. The database is derived from Protein Data Bank (PDB) entries. Relational database technologies are used in a comprehensive cleaning procedure to ensure data uniformity across the whole archive. The search database contains an extensive set of derived properties, goodness-of-fit indicators, and links to other EBI databases including InterPro, GO, and SWISS-PROT, together with links to SCOP, CATH, PFAM and PROSITE. A generic search interface is available, coupled with a fast secondary structure domain search tool.

  4. Macromolecular organization of xyloglucan and cellulose in pea epicotyls

    International Nuclear Information System (INIS)

    Hayashi, T.; Maclachlan, G.

    1984-01-01

    Xyloglucan is known to occur widely in the primary cell walls of higher plants. This polysaccharide in most dicots possesses a cellulose-like main chain with three of every four consecutive residues substituted with xylose and minor addition of other sugars. Xyloglucan and cellulose metabolism is regulated by different processes; since different enzyme systems are probably required for the synthesis of their 1,4-β-linkages. A macromolecular complex composed of xyloglucan and cellulose only was obtained from elongating regions of etiolated pea stems. It was examined by light microscopy using iodine staining, by radioautography after labeling with [ 3 H]fructose, by fluorescence microscopy using a fluorescein-lectin (fructose-binding) as probe, and by electron microscopy after shadowing. The techniques all demonstrated that the macromolecule was present in files of cell shapes, referred to here as cell-wall ghosts, in which xyloglucan was localized both on and between the cellulose microfibrils

  5. Cryo-electron Microscopy Analysis of Structurally Heterogeneous Macromolecular Complexes.

    Science.gov (United States)

    Jonić, Slavica

    2016-01-01

    Cryo-electron microscopy (cryo-EM) has for a long time been a technique of choice for determining structure of large and flexible macromolecular complexes that were difficult to study by other experimental techniques such as X-ray crystallography or nuclear magnetic resonance. However, a fast development of instruments and software for cryo-EM in the last decade has allowed that a large range of complexes can be studied by cryo-EM, and that their structures can be obtained at near-atomic resolution, including the structures of small complexes (e.g., membrane proteins) whose size was earlier an obstacle to cryo-EM. Image analysis to identify multiple coexisting structures in the same specimen (multiconformation reconstruction) is now routinely done both to solve structures at near-atomic resolution and to study conformational dynamics. Methods for multiconformation reconstruction and latest examples of their applications are the focus of this review.

  6. Extracting trends from two decades of microgravity macromolecular crystallization history.

    Science.gov (United States)

    Judge, Russell A; Snell, Edward H; van der Woerd, Mark J

    2005-06-01

    Since the 1980s hundreds of macromolecular crystal growth experiments have been performed in the reduced acceleration environment of an orbiting spacecraft. Significant enhancements in structural knowledge have resulted from X-ray diffraction of the crystals grown. Similarly, many samples have shown no improvement or degradation in comparison to those grown on the ground. A complex series of interrelated factors affect these experiments and by building a comprehensive archive of the results it was aimed to identify factors that result in success and those that result in failure. Specifically, it was found that dedicated microgravity missions increase the chance of success when compared with those where crystallization took place as a parasitic aspect of the mission. It was also found that the chance of success could not be predicted based on any discernible property of the macromolecule available to us.

  7. Macromolecular structure analysis and effective liquefaction pretreatment. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Suuberg, E.M.; Yun, Y.; Lilly, W.D.; Leung, K.; Gates, T.; Otake, Y.; Deevi, S.C.

    1994-07-01

    This project was concerned with characterizing the changes in coal macromolecular structure, that are of significance for liquefaction pretreatments of coal. The macromolecular structure of the insoluble portion of coal is difficult to characterize. Techniques that do so indirectly (based upon, for example, NMR and FTIR characterizations of atomic linkages) are not particularly sensitive for this purpose. Techniques that characterize the elastic structure (such as solvent swelling) are much more sensitive to subtle changes in the network structure. It is for this reason that we focused upon these techniques. The overall objective involved identifying pretreatments that reduce the crosslinking (physical or chemical) of the network structure, and thus lead to materials that can be handled to a greater extent by traditional liquid-phase processing techniques. These techniques tend to be inherently more efficient at producing desirable products. This report is divided into seven chapters. Chapter II summarizes the main experimental approaches used throughout the project, and summarizes the main findings on the Argonne Premium coal samples. Chapter III considers synergistic effects of solvent pairs. It is divided into two subsections. The first is concerned with mixtures of CS{sub 2} with electron donor solvents. The second subsection is concerned with aromatic hydrocarbon - alcohol or hydrocarbon - alcohol mixtures, as might be of interest for preliquefaction delivery of catalysts into bituminous coals. Chapter IV deals with questions of how oxidation might influence the results that are obtained. Chapter V briefly details what conclusions may be drawn concerning the elastic behavior of coals, and the effects of thermal treatments on this behavior. Chapter VI is concerned with theories to describe the action of solvents that are capable of dissociating non-covalent crosslinks. Finally, Chapter VII discusses the practical implications of the study.

  8. Heterogeneity of chromosome damage in [beta]-thalassaemia traits. An evaluation of spontaneous and [gamma]-ray-induced micronuclei and chromosome aberrations in lymphocytes in vitro after G[sub 0] and G[sub 2] phase irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Krishnaja, A.P.; Sharma, N.K. (Bhabha Atomic Research Centre, Bombay (India). Molecular Biology and Agriculture Div.)

    1994-07-01

    This study is an attempt to evaluate the chromosomal radiosensitivity of [beta]-thalassaemia traits compared with healthy individuals from the general population, necessitated by the fact that [beta]-thalassaemia trait is present in 1-17% of different population groups in India and the chances of encountering them in radiation and chemical related industries do exist. Spontaneous chromosome aberration frequencies in peripheral blood lymphocytes from [beta]-thalassaemia traits were found to be in the normal range, whereas significantly higher frequencies of micronuclei (MN) were observed in thalassaemia traits. Based on MN frequency at 2 Gy, [beta]-thalassaemia traits fall into two distinct categories. A hypersensitive group with significant increase in radiation-induced MN over the control group, and a second group with MN frequency slightly above normal individuals. Even when compared with the fitted data at 2 Gy obtained from the pooled results of extensive dose-response investigations from 0.5-5 Gy [gamma]-rays with normal donors for MN, dicentrics and total aberrations, the difference between the means of MN frequencies in [beta]-thalassaemia traits and normals is significant. (author).

  9. Fluid Physics and Macromolecular Crystal Growth in Microgravity

    Science.gov (United States)

    Helliwell, John R.; Snell, Edward H.; Chayen, Naomi E.; Judge, Russell A.; Boggon, Titus J.; Pusey, M. L.; Rose, M. Franklin (Technical Monitor)

    2000-01-01

    The first protein crystallization experiment in microgravity was launched in April, 1981 and used Germany's Technologische Experimente unter Schwerelosigkeit (TEXUS 3) sounding rocket. The protein P-galactosidase (molecular weight 465Kda) was chosen as the sample with a liquid-liquid diffusion growth method. A sliding device brought the protein, buffer and salt solution into contact when microgravity was reached. The sounding rocket gave six minutes of microgravity time with a cine camera and schlieren optics used to monitor the experiment, a single growth cell. In microgravity a strictly laminar diffusion process was observed in contrast to the turbulent convection seen on the ground. Several single crystals, approx 100micron in length, were formed in the flight which were of inferior but of comparable visual quality to those grown on the ground over several days. A second experiment using the same protocol but with solutions cooled to -8C (kept liquid with glycerol antifreeze) again showed laminar diffusion. The science of macromolecular structural crystallography involves crystallization of the macromolecule followed by use of the crystal for X-ray diffraction experiments to determine the three dimensional structure of the macromolecule. Neutron protein crystallography is employed for elucidation of H/D exchange and for improved definition of the bound solvent (D20). The structural information enables an understanding of how the molecule functions with important potential for rational drug design, improved efficiency of industrial enzymes and agricultural chemical development. The removal of turbulent convection and sedimentation in microgravity, and the assumption that higher quality crystals will be produced, has given rise to the growing number of crystallization experiments now flown. Many experiments can be flown in a small volume with simple, largely automated, equipment - an ideal combination for a microgravity experiment. The term "protein crystal growth

  10. Use of Capillaries for Macromolecular Crystallization in a Cryogenic Dewar

    Science.gov (United States)

    Ciszak, Ewa; Hammons, Aaron S.; Hong, Young Soo

    2002-01-01

    The enhanced gaseous nitrogen (EGN) dewar is a cryogenic dry shipper with a sealed cylinder inserted inside along with a temperature monitoring device, and is intended for macromolecular crystallization experiments on the International Space Station. Within the dewar, each crystallization experiment is contained as a solution within a plastic capillary tube. The standard procedure for loading samples in these tubes has involved rapid freezing of the precipitant and biomolecular solution, e.g., protein, directly in liquid nitrogen; this method, however, often resulted in uncontrolled formation of air voids, These air pockets, or bubbles, can lead to irreproducible crystallization results. A novel protocol has been developed to prevent formation of bubbles, and this has been tested in the laboratory as well as aboard the International Space Station during a 42-day long mission of July/August 2001. The gain or loss of mass from solutions within the plastic capillaries revealed that mass transport occurred among separated tubes, and that this mass transport was dependent upon the hygroscopic character of the solution contained in any given tube. The surface area of the plastic capillary tube also related to the observed mass transport. Furthermore, the decreased mass of solutions of-protein correlated to observed formation of protein crystals.

  11. A beamline for macromolecular crystallography at the Advanced Light Source

    International Nuclear Information System (INIS)

    Padmore, H.A.; Earnest, T.; Kim, S.H.; Thompson, A.C.; Robinson, A.L.

    1994-08-01

    A beamline for macromolecular crystallography has been designed for the ALS. The source will be a 37-pole wiggler with a, 2-T on-axis peak field. The wiggler will illuminate three beamlines, each accepting 3 mrad of horizontal aperture. The central beamline will primarily be used for multiple-wavelength anomalous dispersion measurements in the wavelength range from 4 to 0.9 angstrom. The beamline optics will comprise a double-crystal monochromator with a collimating pre-mirror and a double-focusing mirror after the monochromator. The two side stations will be used for fixed-wavelength experiments within the wavelength range from 1.5 to 0.95 angstrom. The optics will consist of a conventional vertically focusing cylindrical mirror followed by an asymmetrically cut curved-crystal monochromator. This paper presents details of the optimization of the wiggler source for crystallography, gives a description of the beamline configuration, and discusses the reasons for the choices made

  12. Macromolecular refinement by model morphing using non-atomic parameterizations.

    Science.gov (United States)

    Cowtan, Kevin; Agirre, Jon

    2018-02-01

    Refinement is a critical step in the determination of a model which explains the crystallographic observations and thus best accounts for the missing phase components. The scattering density is usually described in terms of atomic parameters; however, in macromolecular crystallography the resolution of the data is generally insufficient to determine the values of these parameters for individual atoms. Stereochemical and geometric restraints are used to provide additional information, but produce interrelationships between parameters which slow convergence, resulting in longer refinement times. An alternative approach is proposed in which parameters are not attached to atoms, but to regions of the electron-density map. These parameters can move the density or change the local temperature factor to better explain the structure factors. Varying the size of the region which determines the parameters at a particular position in the map allows the method to be applied at different resolutions without the use of restraints. Potential applications include initial refinement of molecular-replacement models with domain motions, and potentially the use of electron density from other sources such as electron cryo-microscopy (cryo-EM) as the refinement model.

  13. Canadian macromolecular crystallography facility: a suite of fully automated beamlines.

    Science.gov (United States)

    Grochulski, Pawel; Fodje, Michel; Labiuk, Shaunivan; Gorin, James; Janzen, Kathryn; Berg, Russ

    2012-06-01

    The Canadian light source is a 2.9 GeV national synchrotron radiation facility located on the University of Saskatchewan campus in Saskatoon. The small-gap in-vacuum undulator illuminated beamline, 08ID-1, together with the bending magnet beamline, 08B1-1, constitute the Canadian Macromolecular Crystallography Facility (CMCF). The CMCF provides service to more than 50 Principal Investigators in Canada and the United States. Up to 25% of the beam time is devoted to commercial users and the general user program is guaranteed up to 55% of the useful beam time through a peer-review process. CMCF staff provides "Mail-In" crystallography service to users with the highest scored proposals. Both beamlines are equipped with very robust end-stations including on-axis visualization systems, Rayonix 300 CCD series detectors and Stanford-type robotic sample auto-mounters. MxDC, an in-house developed beamline control system, is integrated with a data processing module, AutoProcess, allowing full automation of data collection and data processing with minimal human intervention. Sample management and remote monitoring of experiments is enabled through interaction with a Laboratory Information Management System developed at the facility.

  14. Macromolecular Crystallography and Structural Biology Databases at NIST.

    Science.gov (United States)

    Gilliland, G L

    2001-01-01

    In the late 1970s, macromolecular crystallography at NIST began with collaboration between NIST and NIH to establish a single-crystal neutron diffractometer. This instrument was constructed and employed to solve a number of crystal structures: bovine ribonuclease A, bovine-ribonuclease-uridine vanadate complex, and porcine insulin. In the mid 1980s a Biomolecular Structure Group was created establishing NIST capabilities in biomolecular singe-crystal x-ray diffraction. The group worked on a variety of structural problems until joining the NIST/UMBI Center for Advanced Research in Biotechnology (CARB) in 1987. Crystallographic studies at CARB were then focused on protein engineering efforts that included among others chymosin, subtilisin BPN', interleukin 1β, and glutathione S-transferase. Recently, the structural biology efforts have centered on enzymes in the chorismate metabolic pathways involved in amino acid biosynthesis and in structural genomics that involves determining the structures of "hypothetical" proteins to aid in assigning function. In addition to crystallographic studies, structural biology database activities began with the formal establishment of the Biological Macro-molecule Crystallization Database in 1989. Later, in 1997, NIST in partnership with Rutgers and UCSD formed the Research Collaboratory for Structural Bioinformatics that successfully acquired the Protein Data Bank. The NIST efforts in these activities have focused on data uniformity, establishing and maintaining the physical archive, and working with the NMR community.

  15. On macromolecular refinement at subatomic resolution with interatomic scatterers

    Energy Technology Data Exchange (ETDEWEB)

    Afonine, Pavel V., E-mail: pafonine@lbl.gov; Grosse-Kunstleve, Ralf W.; Adams, Paul D. [Lawrence Berkeley National Laboratory, One Cyclotron Road, BLDG 64R0121, Berkeley, CA 94720 (United States); Lunin, Vladimir Y. [Institute of Mathematical Problems of Biology, Russian Academy of Sciences, Pushchino 142290 (Russian Federation); Urzhumtsev, Alexandre [IGMBC, 1 Rue L. Fries, 67404 Illkirch and IBMC, 15 Rue R. Descartes, 67084 Strasbourg (France); Faculty of Sciences, Nancy University, 54506 Vandoeuvre-lès-Nancy (France); Lawrence Berkeley National Laboratory, One Cyclotron Road, BLDG 64R0121, Berkeley, CA 94720 (United States)

    2007-11-01

    Modelling deformation electron density using interatomic scatters is simpler than multipolar methods, produces comparable results at subatomic resolution and can easily be applied to macromolecules. A study of the accurate electron-density distribution in molecular crystals at subatomic resolution (better than ∼1.0 Å) requires more detailed models than those based on independent spherical atoms. A tool that is conventionally used in small-molecule crystallography is the multipolar model. Even at upper resolution limits of 0.8–1.0 Å, the number of experimental data is insufficient for full multipolar model refinement. As an alternative, a simpler model composed of conventional independent spherical atoms augmented by additional scatterers to model bonding effects has been proposed. Refinement of these mixed models for several benchmark data sets gave results that were comparable in quality with the results of multipolar refinement and superior to those for conventional models. Applications to several data sets of both small molecules and macromolecules are shown. These refinements were performed using the general-purpose macromolecular refinement module phenix.refine of the PHENIX package.

  16. Timely deposition of macromolecular structures is necessary for peer review

    International Nuclear Information System (INIS)

    Joosten, Robbie P.; Soueidan, Hayssam; Wessels, Lodewyk F. A.; Perrakis, Anastassis

    2013-01-01

    Deposition of crystallographic structures should be concurrent with or prior to manuscript submission for peer review, enabling validation and increasing reliability of the PDB. Most of the macromolecular structures in the Protein Data Bank (PDB), which are used daily by thousands of educators and scientists alike, are determined by X-ray crystallography. It was examined whether the crystallographic models and data were deposited to the PDB at the same time as the publications that describe them were submitted for peer review. This condition is necessary to ensure pre-publication validation and the quality of the PDB public archive. It was found that a significant proportion of PDB entries were submitted to the PDB after peer review of the corresponding publication started, and many were only submitted after peer review had ended. It is argued that clear description of journal policies and effective policing is important for pre-publication validation, which is key in ensuring the quality of the PDB and of peer-reviewed literature

  17. Synchrotron radiation macromolecular crystallography: science and spin-offs.

    Science.gov (United States)

    Helliwell, John R; Mitchell, Edward P

    2015-03-01

    A current overview of synchrotron radiation (SR) in macromolecular crystallography (MX) instrumentation, methods and applications is presented. Automation has been and remains a central development in the last decade, as have the rise of remote access and of industrial service provision. Results include a high number of Protein Data Bank depositions, with an increasing emphasis on the successful use of microcrystals. One future emphasis involves pushing the frontiers of using higher and lower photon energies. With the advent of X-ray free-electron lasers, closely linked to SR developments, the use of ever smaller samples such as nanocrystals, nanoclusters and single molecules is anticipated, as well as the opening up of femtosecond time-resolved diffraction structural studies. At SR sources, a very high-throughput assessment for the best crystal samples and the ability to tackle just a few micron and sub-micron crystals will become widespread. With higher speeds and larger detectors, diffraction data volumes are becoming long-term storage and archiving issues; the implications for today and the future are discussed. Together with the rise of the storage ring to its current pre-eminence in MX data provision, the growing tendency of central facility sites to offer other centralized facilities complementary to crystallography, such as cryo-electron microscopy and NMR, is a welcome development.

  18. Macromolecular Diffusion in Self-Assembling Biodegradable Thermosensitive Hydrogels

    Science.gov (United States)

    Vermonden, Tina; Jena, Sidhartha S.; Barriet, David; Censi, Roberta; van der Gucht, Jasper; Hennink, Wim E.; Siegel, Ronald A.

    2009-01-01

    Hydrogel formation triggered by a change in temperature is an attractive mechanism for in situ gelling biomaterials for pharmaceutical applications such as the delivery of therapeutic proteins. In this study, hydrogels were prepared from ABA triblock polymers having thermosensitive poly(N-(2-hydroxypropyl) methacrylamide lactate) flanking A-blocks and hydrophilic poly(ethylene glycol) B-blocks. Polymers with fixed length A blocks (~22 kDA) but differing PEG-midblock lengths (2, 4 and 10 kDa) were synthesized and dissolved in water with dilute fluorescein isothiocyanate (FITC)-labeled dextrans (70 and 500 kDA). Hydrogels encapsulating the dextrans were formed by raising the temperature. Fluorescence recovery after photobleaching (FRAP) studies showed that diffusion coefficients and mobile fractions of the dextran dyes decreased upon elevating temperatures above 25 °C. Confocal laser scanning microscopy and cryo-SEM demonstrated that hydrogel structure depended on PEG block length. Phase separation into polymer-rich and water-rich domains occurred to a larger extent for polymers with small PEG blocks compared to polymers with a larger PEG block. By changing the PEG block length and thereby the hydrogel structure, mobility of FITC-dextran could be tailored. At physiological pH the hydrogels degraded over time by ester hydrolysis, resulting in increased mobility of the encapsulated dye. Since diffusion can be controlled according to polymer design and concentration, plus temperature, these biocompatible hydrogels are attractive as potential in situ gelling biodegradable materials for macromolecular drug delivery. PMID:20885989

  19. Macromolecular Diffusion in Self-Assembling Biodegradable Thermosensitive Hydrogels.

    Science.gov (United States)

    Vermonden, Tina; Jena, Sidhartha S; Barriet, David; Censi, Roberta; van der Gucht, Jasper; Hennink, Wim E; Siegel, Ronald A

    2010-01-26

    Hydrogel formation triggered by a change in temperature is an attractive mechanism for in situ gelling biomaterials for pharmaceutical applications such as the delivery of therapeutic proteins. In this study, hydrogels were prepared from ABA triblock polymers having thermosensitive poly(N-(2-hydroxypropyl) methacrylamide lactate) flanking A-blocks and hydrophilic poly(ethylene glycol) B-blocks. Polymers with fixed length A blocks (~22 kDA) but differing PEG-midblock lengths (2, 4 and 10 kDa) were synthesized and dissolved in water with dilute fluorescein isothiocyanate (FITC)-labeled dextrans (70 and 500 kDA). Hydrogels encapsulating the dextrans were formed by raising the temperature. Fluorescence recovery after photobleaching (FRAP) studies showed that diffusion coefficients and mobile fractions of the dextran dyes decreased upon elevating temperatures above 25 °C. Confocal laser scanning microscopy and cryo-SEM demonstrated that hydrogel structure depended on PEG block length. Phase separation into polymer-rich and water-rich domains occurred to a larger extent for polymers with small PEG blocks compared to polymers with a larger PEG block. By changing the PEG block length and thereby the hydrogel structure, mobility of FITC-dextran could be tailored. At physiological pH the hydrogels degraded over time by ester hydrolysis, resulting in increased mobility of the encapsulated dye. Since diffusion can be controlled according to polymer design and concentration, plus temperature, these biocompatible hydrogels are attractive as potential in situ gelling biodegradable materials for macromolecular drug delivery.

  20. Adaptation to extreme environments: macromolecular dynamics in bacteria compared in vivo by neutron scattering.

    Science.gov (United States)

    Tehei, Moeava; Franzetti, Bruno; Madern, Dominique; Ginzburg, Margaret; Ginzburg, Ben Z; Giudici-Orticoni, Marie-Thérèse; Bruschi, Mireille; Zaccai, Giuseppe

    2004-01-01

    Mean macromolecular dynamics was quantified in vivo by neutron scattering in psychrophile, mesophile, thermophile and hyperthermophile bacteria. Root mean square atomic fluctuation amplitudes determining macromolecular flexibility were found to be similar for each organism at its physiological temperature ( approximately 1 A in the 0.1 ns timescale). Effective force constants determining the mean macromolecular resilience were found to increase with physiological temperature from 0.2 N/m for the psychrophiles, which grow at 4 degrees C, to 0.6 N/m for the hyperthermophiles (85 degrees C), indicating that the increase in stabilization free energy is dominated by enthalpic rather than entropic terms. Larger resilience allows macromolecular stability at high temperatures, while maintaining flexibility within acceptable limits for biological activity.

  1. Spontaneous Atraumatic Mediastinal Hemorrhage

    Directory of Open Access Journals (Sweden)

    Morkos Iskander BSc, BMBS, MRCS, PGCertMedEd

    2013-04-01

    Full Text Available Spontaneous atraumatic mediastinal hematomas are rare. We present a case of a previously fit and well middle-aged lady who presented with acute breathlessness and an increasing neck swelling and spontaneous neck bruising. On plain chest radiograph, widening of the mediastinum was noted. The bruising was later confirmed to be secondary to mediastinal hematoma. This life-threatening diagnostic conundrum was managed conservatively with a multidisciplinary team approach involving upper gastrointestinal and thoracic surgeons, gastroenterologists, radiologists, intensivists, and hematologists along with a variety of diagnostic modalities. A review of literature is also presented to help surgeons manage such challenging and complicated cases.

  2. Spontaneous Appendicocutaneous Fistula I

    African Journals Online (AJOL)

    M T0k0de* MB, BS and. Dr 0. A. AWOj0bi+ FMCS (Nig). ABSTRACT. Ruptured appendicitis is not a common cause of spontaneous enterocutaneous fistula. A case of ruptured retrocaecal appendicitis presenting as an enterocutaneous fistula in a Nigerian woman is presented. The literature on this disorder is also reviewed.

  3. [Spontaneous bacterial peritonitis].

    Science.gov (United States)

    Strauss, Edna; Caly, Wanda Regina

    2003-01-01

    Spontaneous bacterial peritonitis occurs in 30% of patients with ascites due to cirrhosis leading to high morbidity and mortality rates. The pathogenesis of spontaneous bacterial peritonitis is related to altered host defenses observed in end-stage liver disease, overgrowth of microorganisms, and bacterial translocation from the intestinal lumen to mesenteric lymph nodes. Clinical manifestations vary from severe to slight or absent, demanding analysis of the ascitic fluid. The diagnosis is confirmed by a number of neutrophils over 250/mm3 associated or not to bacterial growth in culture of an ascites sample. Enterobacteriae prevail and Escherichia coli has been the most frequent bacterium reported. Mortality rates decreased markedly in the last two decades due to early diagnosis and prompt antibiotic treatment. Third generation intravenous cephalosporins are effective in 70% to 95% of the cases. Recurrence of spontaneous bacterial peritonitis is common and can be prevented by the continuous use of oral norfloxacin. The development of bacterial resistance demands the search for new options in the prophylaxis of spontaneous bacterial peritonitis; probiotics are a promising new approach, but deserve further evaluation. Short-term antibiotic prophylaxis is recommended for patients with cirrhosis and ascites shortly after an acute episode of gastrointestinal bleeding.

  4. Spontaneous Grammar Explanations.

    Science.gov (United States)

    Tjoo, Hong Sing; Lewis, Marilyn

    1998-01-01

    Describes one New Zealand university language teacher's reflection on her own grammar explanations to university-level students of Bahasa Indonesian. Examines form-focused instruction through the teacher's spontaneous answers to students' questions about the form of the language they are studying. The teacher's experiences show that it takes time…

  5. EDITORIAL SPONTANEOUS BACTERIAL PERITONITIS ...

    African Journals Online (AJOL)

    hi-tech

    Spontaneous bacterial peritonitis (SBP) frequent]y occurs in patients with liver cirrhosis and ascites. It is defined as an infection of previously sterile ascitic fluid without any demonstrable intrabdominal source of infection. It is now internationally agreed that a polymorphonuclear (PMN) cell count in the ascitic fluid of over 250 ...

  6. Spontaneous dimensional reduction?

    Science.gov (United States)

    Carlip, Steven

    2012-10-01

    Over the past few years, evidence has begun to accumulate suggesting that spacetime may undergo a "spontaneous dimensional reduction" to two dimensions near the Planck scale. I review some of this evidence, and discuss the (still very speculative) proposal that the underlying mechanism may be related to short-distance focusing of light rays by quantum fluctuations.

  7. Development of an online UV-visible microspectrophotometer for a macromolecular crystallography beamline.

    Science.gov (United States)

    Shimizu, Nobutaka; Shimizu, Tetsuya; Baba, Seiki; Hasegawa, Kazuya; Yamamoto, Masaki; Kumasaka, Takashi

    2013-11-01

    Measurement of the UV-visible absorption spectrum is a convenient technique for detecting chemical changes of proteins, and it is therefore useful to combine spectroscopy and diffraction studies. An online microspectrophotometer for the UV-visible region was developed and installed on the macromolecular crystallography beamline, BL38B1, at SPring-8. This spectrophotometer is equipped with a difference dispersive double monochromator, a mercury-xenon lamp as the light source, and a photomultiplier as the detector. The optical path is mostly constructed using mirrors, in order to obtain high brightness in the UV region, and the confocal optics are assembled using a cross-slit diaphragm like an iris to eliminate stray light. This system can measure optical densities up to a maximum of 4.0. To study the effect of radiation damage, preliminary measurements of glucose isomerase and thaumatin crystals were conducted in the UV region. Spectral changes dependent on X-ray dose were observed at around 280 nm, suggesting that structural changes involving Trp or Tyr residues occurred in the protein crystal. In the case of the thaumatin crystal, a broad peak around 400 nm was also generated after X-ray irradiation, suggesting the cleavage of a disulfide bond. Dose-dependent spectral changes were also observed in cryo-solutions alone, and these changes differed with the composition of the cryo-solution. These responses in the UV region are informative regarding the state of the sample; consequently, this device might be useful for X-ray crystallography.

  8. Macromolecular compositions of phytoplankton in the Amundsen Sea, Antarctica

    Science.gov (United States)

    Kim, Bo Kyung; Lee, Jang Han; Joo, HuiTae; Song, Ho Jung; Yang, Eun Jin; Lee, Sang Hoon; Lee, Sang H.

    2016-01-01

    The biochemical compositions (proteins, carbohydrates, and lipids) of phytoplankton provide useful information for their environmental growth conditions and nutritional status as a basic food source for upper trophic consumers. Concentrations of these compositions were assessed at 100, 30, and 1% light penetration depths within the euphotic zone in the Amundsen Sea, Antarctica, using colorimetric techniques. The major inorganic nutrients were generally abundant throughout the study area. The average chlorophyll a (chl-a) concentration was 49.2 mg m-2 (S.D.=±27.6 mg m-2) and large phytoplankton (>20 μm) accounted for 64.1% of the total chl-a concentration. The biochemical compositions of the phytoplankton were not significantly different among different light depths or productivity stations. The overall compositions of proteins, carbohydrates, and lipids from all stations averaged 65.9% (S.D.=±12.5%), 22.4% (S.D.=±10.9%), and 11.7% (S.D.=±6.5%), respectively. Regardless of dominant phytoplankton species, nitrogen-abundant conditions sustained high protein compositions of phytoplankton in the Amundsen Sea during the cruise period. Based on the macromolecular compositions, the average food material (FM) concentration was 219.4 μg L-1 (S.D.=±151.1 μg L-1) and correlated positively with the primary productivity in the Amundsen Sea. High protein/carbohydrate ratios (>1) and large proportions of proteins suggest that phytoplankton provide nitrogen-sufficient foods to higher trophic consumers through a higher efficiency of protein carbon incorporated into herbivores.

  9. A Compact X-Ray System for Macromolecular Crystallography. 5

    Science.gov (United States)

    Gubarev, Mikhail; Ciszak, Ewa; Ponomarev, Igor; Joy, Marshall

    2000-01-01

    We describe the design and performance of a high flux x-ray system for macromolecular crystallography that combines a microfocus x-ray generator (40 gm FWHM spot size at a power level of 46.5Watts) and a 5.5 mm focal distance polycapillary optic. The Cu K(sub alpha) X-ray flux produced by this optimized system is 7.0 times above the X-ray flux previously reported. The X-ray flux from the microfocus system is also 3.2 times higher than that produced by the rotating anode generator equipped with a long focal distance graded multilayer monochromator (Green optic; CMF24-48-Cu6) and 30% less than that produced by the rotating anode generator with the newest design of graded multilayer monochromator (Blue optic; CMF12-38-Cu6). Both rotating anode generators operate at a power level of 5000 Watts, dissipating more than 100 times the power of our microfocus x-ray system. Diffraction data collected from small test crystals are of high quality. For example, 42,540 reflections collected at ambient temperature from a lysozyme crystal yielded R(sub sym) 5.0% for the data extending to 1.7A, and 4.8% for the complete set of data to 1.85A. The amplitudes of the reflections were used to calculate difference electron density maps that revealed positions of structurally important ions and water molecules in the crystal of lysozyme using the phases calculated from the protein model.

  10. A Compact X-Ray System for Macromolecular Crystallography

    Science.gov (United States)

    Gubarev, Mikhail; Ciszak, Ewa; Ponomarev, Igor; Gibson, Walter; Joy, Marshall

    2000-01-01

    We describe the design and performance of a high flux x-ray system for a macromolecular crystallography that combines a microfocus x-ray generator (40 micrometer full width at half maximum spot size at a power level of 46.5 W) and a collimating polycapillary optic. The Cu Ka lpha x-ray flux produced by this optimized system through a 500,um diam orifice is 7.0 times greater than the x-ray flux previously reported by Gubarev et al. [M. Gubarev et al., J. Appl. Crystallogr. 33, 882 (2000)]. The x-ray flux from the microfocus system is also 2.6 times higher than that produced by a rotating anode generator equipped with a graded multilayer monochromator (green optic, Osmic Inc. CMF24-48-Cu6) and 40% less than that produced by a rotating anode generator with the newest design of graded multilayer monochromator (blue optic, Osmic, Inc. CMF12-38-Cu6). Both rotating anode generators operate at a power level of 5000 W, dissipating more than 100 times the power of our microfocus x-ray system. Diffraction data collected from small test crystals are of high quality. For example, 42 540 reflections collected at ambient temperature from a lysozyme crystal yielded R(sub sym)=5.0% for data extending to 1.70 A, and 4.8% for the complete set of data to 1.85 A. The amplitudes of the observed reflections were used to calculate difference electron density maps that revealed positions of structurally important ions and water molecules in the crystal of lysozyme using the phases calculated from the protein model.

  11. Macromolecular query language (MMQL): prototype data model and implementation.

    Science.gov (United States)

    Shindyalov, I N; Chang, W; Pu, C; Bourne, P E

    1994-11-01

    Macromolecular query language (MMQL) is an extensible interpretive language in which to pose questions concerning the experimental or derived features of the 3-D structure of biological macromolecules. MMQL portends to be intuitive with a simple syntax, so that from a user's perspective complex queries are easily written. A number of basic queries and a more complex query--determination of structures containing a five-strand Greek key motif--are presented to illustrate the strengths and weaknesses of the language. The predominant features of MMQL are a filter and pattern grammar which are combined to express a wide range of interesting biological queries. Filters permit the selection of object attributes, for example, compound name and resolution, whereas the patterns currently implemented query primary sequence, close contacts, hydrogen bonding, secondary structure, conformation and amino acid properties (volume, polarity, isoelectric point, hydrophobicity and different forms of exposure). MMQL queries are processed by MMQLlib; a C++ class library, to which new query methods and pattern types are easily added. The prototype implementation described uses PDBlib, another C(++)-based class library from representing the features of biological macromolecules at the level of detail parsable from a PDB file. Since PDBlib can represent data stored in relational and object-oriented databases, as well as PDB files, once these data are loaded they too can be queried by MMQL. Performance metrics are given for queries of PDB files for which all derived data are calculated at run time and compared to a preliminary version of OOPDB, a prototype object-oriented database with a schema based on a persistent version of PDBlib which offers more efficient data access and the potential to maintain derived information. MMQLlib, PDBlib and associated software are available via anonymous ftp from cuhhca.hhmi.columbia.edu.

  12. Spontaneous healing of spontaneous coronary artery dissection.

    Science.gov (United States)

    Almafragi, Amar; Convens, Carl; Heuvel, Paul Van Den

    2010-01-01

    Spontaneous coronary artery dissection (SCAD) is a rare cause of acute coronary syndrome and sudden cardiac death. It should be suspected in every healthy young woman without cardiac risk factors, especially during the peripartum or postpartum periods. It is important to check for a history of drug abuse, collagen vascular disease or blunt trauma of the chest. Coronary angiography is essential for diagnosis and early management. We wonder whether thrombolysis might aggravate coronary dissection. All types of treatment (medical therapy, percutaneous intervention or surgery) improve the prognosis without affecting survival times if used appropriately according to the clinical stability and the angiographic features of the involved coronary arteries. Prompt recognition and targeted treatment improve outcomes. We report a case of SCAD in a young female free of traditional cardiovascular risk factors, who presented six hours after thrombolysis for ST elevation myocardial infarction. Coronary angiography showed a dissection of the left anterior descending and immediate branch. She had successful coronary artery bypass grafting, with complete healing of left anterior descending dissection.

  13. Spontaneous spinal epidural abscess.

    LENUS (Irish Health Repository)

    Ellanti, P

    2011-10-01

    Spinal epidural abscess is an uncommon entity, the frequency of which is increasing. They occur spontaneously or as a complication of intervention. The classical triad of fever, back pain and neurological symptoms are not always present. High index of suspicion is key to diagnosis. Any delay in diagnosis and treatment can have significant neurological consequences. We present the case of a previously well man with a one month history of back pain resulting from an epidural abscess.

  14. Towards a compact and precise sample holder for macromolecular crystallography.

    Science.gov (United States)

    Papp, Gergely; Rossi, Christopher; Janocha, Robert; Sorez, Clement; Lopez-Marrero, Marcos; Astruc, Anthony; McCarthy, Andrew; Belrhali, Hassan; Bowler, Matthew W; Cipriani, Florent

    2017-10-01

    Most of the sample holders currently used in macromolecular crystallography offer limited storage density and poor initial crystal-positioning precision upon mounting on a goniometer. This has now become a limiting factor at high-throughput beamlines, where data collection can be performed in a matter of seconds. Furthermore, this lack of precision limits the potential benefits emerging from automated harvesting systems that could provide crystal-position information which would further enhance alignment at beamlines. This situation provided the motivation for the development of a compact and precise sample holder with corresponding pucks, handling tools and robotic transfer protocols. The development process included four main phases: design, prototype manufacture, testing with a robotic sample changer and validation under real conditions on a beamline. Two sample-holder designs are proposed: NewPin and miniSPINE. They share the same robot gripper and allow the storage of 36 sample holders in uni-puck footprint-style pucks, which represents 252 samples in a dry-shipping dewar commonly used in the field. The pucks are identified with human- and machine-readable codes, as well as with radio-frequency identification (RFID) tags. NewPin offers a crystal-repositioning precision of up to 10 µm but requires a specific goniometer socket. The storage density could reach 64 samples using a special puck designed for fully robotic handling. miniSPINE is less precise but uses a goniometer mount compatible with the current SPINE standard. miniSPINE is proposed for the first implementation of the new standard, since it is easier to integrate at beamlines. An upgraded version of the SPINE sample holder with a corresponding puck named SPINEplus is also proposed in order to offer a homogenous and interoperable system. The project involved several European synchrotrons and industrial companies in the fields of consumables and sample-changer robotics. Manual handling of mini

  15. Path Similarity Analysis: A Method for Quantifying Macromolecular Pathways.

    Directory of Open Access Journals (Sweden)

    Sean L Seyler

    2015-10-01

    Full Text Available Diverse classes of proteins function through large-scale conformational changes and various sophisticated computational algorithms have been proposed to enhance sampling of these macromolecular transition paths. Because such paths are curves in a high-dimensional space, it has been difficult to quantitatively compare multiple paths, a necessary prerequisite to, for instance, assess the quality of different algorithms. We introduce a method named Path Similarity Analysis (PSA that enables us to quantify the similarity between two arbitrary paths and extract the atomic-scale determinants responsible for their differences. PSA utilizes the full information available in 3N-dimensional configuration space trajectories by employing the Hausdorff or Fréchet metrics (adopted from computational geometry to quantify the degree of similarity between piecewise-linear curves. It thus completely avoids relying on projections into low dimensional spaces, as used in traditional approaches. To elucidate the principles of PSA, we quantified the effect of path roughness induced by thermal fluctuations using a toy model system. Using, as an example, the closed-to-open transitions of the enzyme adenylate kinase (AdK in its substrate-free form, we compared a range of protein transition path-generating algorithms. Molecular dynamics-based dynamic importance sampling (DIMS MD and targeted MD (TMD and the purely geometric FRODA (Framework Rigidity Optimized Dynamics Algorithm were tested along with seven other methods publicly available on servers, including several based on the popular elastic network model (ENM. PSA with clustering revealed that paths produced by a given method are more similar to each other than to those from another method and, for instance, that the ENM-based methods produced relatively similar paths. PSA applied to ensembles of DIMS MD and FRODA trajectories of the conformational transition of diphtheria toxin, a particularly challenging example

  16. Contribution of Macromolecular Antioxidants to Dietary Antioxidant Capacity: A Study in the Spanish Mediterranean Diet.

    Science.gov (United States)

    Pérez-Jiménez, Jara; Díaz-Rubio, M Elena; Saura-Calixto, Fulgencio

    2015-12-01

    Epidemiological and clinical studies show that diets with a high antioxidant capacity, such us those rich in plant food and beverages, are associated with significant decreases in the overall risk of cardiovascular disease or colorectal cancer. Current studies on dietary antioxidants and dietary antioxidant capacity focus exclusively on low molecular weight or soluble antioxidants (vitamins C and E, phenolic compounds and carotenoids), ignoring macromolecular antioxidants. These are polymeric phenolic compounds or polyphenols and carotenoids linked to plant food macromolecules that yield bioavailable metabolites by the action of the microbiota with significant effects either local and/or systemic after absorption. This study determined the antioxidant capacity of the Spanish Mediterranean diet including for the first time both soluble and macromolecular antioxidants. Antioxidant capacity and consumption data of the 54 most consumed plant foods and beverages were used. Results showed that macromolecular antioxidants are the major dietary antioxidants, contributing a 61% to the diet antioxidant capacity (8000 μmol Trolox, determined by ABTS method). The antioxidant capacity data for foods and beverages provided here may be used to estimate the dietary antioxidant capacity in different populations, where similar contributions of macromolecular antioxidants may be expected, and also to design antioxidant-rich diets. Including macromolecular antioxidants in mechanistic, intervention and observational studies on dietary antioxidants may contribute to a better understanding of the role of antioxidants in nutrition and health.

  17. Fifteen years of the Protein Crystallography Station: the coming of age of macromolecular neutron crystallography.

    Science.gov (United States)

    Chen, Julian C-H; Unkefer, Clifford J

    2017-01-01

    The Protein Crystallography Station (PCS), located at the Los Alamos Neutron Scattering Center (LANSCE), was the first macromolecular crystallography beamline to be built at a spallation neutron source. Following testing and commissioning, the PCS user program was funded by the Biology and Environmental Research program of the Department of Energy Office of Science (DOE-OBER) for 13 years (2002-2014). The PCS remained the only dedicated macromolecular neutron crystallography station in North America until the construction and commissioning of the MaNDi and IMAGINE instruments at Oak Ridge National Laboratory, which started in 2012. The instrument produced a number of research and technical outcomes that have contributed to the field, clearly demonstrating the power of neutron crystallo-graphy in helping scientists to understand enzyme reaction mechanisms, hydrogen bonding and visualization of H-atom positions, which are critical to nearly all chemical reactions. During this period, neutron crystallography became a technique that increasingly gained traction, and became more integrated into macromolecular crystallography through software developments led by investigators at the PCS. This review highlights the contributions of the PCS to macromolecular neutron crystallography, and gives an overview of the history of neutron crystallography and the development of macromolecular neutron crystallography from the 1960s to the 1990s and onwards through the 2000s.

  18. Detection of Macromolecular Fractions in HCN Polymers Using Electrophoretic and Ultrafiltration Techniques.

    Science.gov (United States)

    Marín-Yaseli, Margarita R; Cid, Cristina; Yagüe, Ana I; Ruiz-Bermejo, Marta

    2017-02-01

    Elucidating the origin of life involves synthetic as well as analytical challenges. Herein, for the first time, we describe the use of gel electrophoresis and ultrafiltration to fractionate HCN polymers. Since the first prebiotic synthesis of adenine by Oró, HCN polymers have gained much interest in studies on the origins of life due to the identification of biomonomers and related compounds within them. Here, we demonstrate that macromolecular fractions with electrophoretic mobility can also be detected within HCN polymers. The migration of polymers under the influence of an electric field depends not only on their sizes (one-dimensional electrophoresis) but also their different isoelectric points (two-dimensional electrophoresis, 2-DE). The same behaviour was observed for several macromolecular fractions detected in HCN polymers. Macromolecular fractions with apparent molecular weights as high as 250 kDa were detected by tricine-SDS gel electrophoresis. Cationic macromolecular fractions with apparent molecular weights as high as 140 kDa were also detected by 2-DE. The HCN polymers synthesized were fractionated by ultrafiltration. As a result, the molecular weight distributions of the macromolecular fractions detected in the HCN polymers directly depended on the synthetic conditions used to produce these polymers. The implications of these results for prebiotic chemistry will be discussed. © 2017 Wiley-VHCA AG, Zurich, Switzerland.

  19. PDBe: improved accessibility of macromolecular structure data from PDB and EMDB.

    Science.gov (United States)

    Velankar, Sameer; van Ginkel, Glen; Alhroub, Younes; Battle, Gary M; Berrisford, John M; Conroy, Matthew J; Dana, Jose M; Gore, Swanand P; Gutmanas, Aleksandras; Haslam, Pauline; Hendrickx, Pieter M S; Lagerstedt, Ingvar; Mir, Saqib; Fernandez Montecelo, Manuel A; Mukhopadhyay, Abhik; Oldfield, Thomas J; Patwardhan, Ardan; Sanz-García, Eduardo; Sen, Sanchayita; Slowley, Robert A; Wainwright, Michael E; Deshpande, Mandar S; Iudin, Andrii; Sahni, Gaurav; Salavert Torres, Jose; Hirshberg, Miriam; Mak, Lora; Nadzirin, Nurul; Armstrong, David R; Clark, Alice R; Smart, Oliver S; Korir, Paul K; Kleywegt, Gerard J

    2016-01-04

    The Protein Data Bank in Europe (http://pdbe.org) accepts and annotates depositions of macromolecular structure data in the PDB and EMDB archives and enriches, integrates and disseminates structural information in a variety of ways. The PDBe website has been redesigned based on an analysis of user requirements, and now offers intuitive access to improved and value-added macromolecular structure information. Unique value-added information includes lists of reviews and research articles that cite or mention PDB entries as well as access to figures and legends from full-text open-access publications that describe PDB entries. A powerful new query system not only shows all the PDB entries that match a given query, but also shows the 'best structures' for a given macromolecule, ligand complex or sequence family using data-quality information from the wwPDB validation reports. A PDBe RESTful API has been developed to provide unified access to macromolecular structure data available in the PDB and EMDB archives as well as value-added annotations, e.g. regarding structure quality and up-to-date cross-reference information from the SIFTS resource. Taken together, these new developments facilitate unified access to macromolecular structure data in an intuitive way for non-expert users and support expert users in analysing macromolecular structure data. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

  20. The use of a mini-κ goniometer head in macromolecular crystallography diffraction experiments.

    Science.gov (United States)

    Brockhauser, Sandor; Ravelli, Raimond B G; McCarthy, Andrew A

    2013-07-01

    Most macromolecular crystallography (MX) diffraction experiments at synchrotrons use a single-axis goniometer. This markedly contrasts with small-molecule crystallography, in which the majority of the diffraction data are collected using multi-axis goniometers. A novel miniaturized κ-goniometer head, the MK3, has been developed to allow macromolecular crystals to be aligned. It is available on the majority of the structural biology beamlines at the ESRF, as well as elsewhere. In addition, the Strategy for the Alignment of Crystals (STAC) software package has been developed to facilitate the use of the MK3 and other similar devices. Use of the MK3 and STAC is streamlined by their incorporation into online analysis tools such as EDNA. The current use of STAC and MK3 on the MX beamlines at the ESRF is discussed. It is shown that the alignment of macromolecular crystals can result in improved diffraction data quality compared with data obtained from randomly aligned crystals.

  1. Spontaneous Thigh Compartment Syndrome

    Directory of Open Access Journals (Sweden)

    Khan, Sameer K

    2011-02-01

    Full Text Available A young man presented with a painful and swollen thigh, without any history of trauma, illness, coagulopathic medication or recent exertional exercise. Preliminary imaging delineated a haematoma in the anterior thigh, without any fractures or muscle trauma. Emergent fasciotomies were performed. No pathology could be identified intra-operatively, or on follow-up imaging. A review of thigh compartment syndromes described in literature is presented in a table. Emergency physicians and traumatologists should be cognisant of spontaneous atraumatic presentations of thigh compartment syndrome, to ensure prompt referral and definitive management of this limb-threatening condition. [West J Emerg Med. 2011;12(1:134-138].

  2. Aging changes of macromolecular synthesis in the mitochondria of mouse hepatocytes as revealed by microscopic radioautography

    Energy Technology Data Exchange (ETDEWEB)

    Nagata, Tetsuji [Shinshu University, Matsumoto (Japan). Dept. of Anatomy and Cell Biology

    2007-07-01

    This mini-review reports aging changes of macromolecular synthesis in the mitochondria of mouse hepatocytes. We have observed the macromolecular synthesis, such as DNA, RNA and proteins, in the mitochondria of various mammalian cells by means of electron microscopic radioautography technique developed in our laboratory. The number of mitochondria per cell, number of labeled mitochondria per cell with 3H-thymidine, 3H-uridine and 3H-leucine, precursors for DNA, RNA and proteins, respectively, were counted and the labeling indices at various ages, from fetal to postnatal early days and several months to 1 and 2 years in senescence, were calculated, which showed variations due to aging. (author)

  3. An acoustic on-chip goniometer for room temperature macromolecular crystallography.

    Science.gov (United States)

    Burton, C G; Axford, D; Edwards, A M J; Gildea, R J; Morris, R H; Newton, M I; Orville, A M; Prince, M; Topham, P D; Docker, P T

    2017-12-05

    This paper describes the design, development and successful use of an on-chip goniometer for room-temperature macromolecular crystallography via acoustically induced rotations. We present for the first time a low cost, rate-tunable, acoustic actuator for gradual in-fluid sample reorientation about varying axes and its utilisation for protein structure determination on a synchrotron beamline. The device enables the efficient collection of diffraction data via a rotation method from a sample within a surface confined droplet. This method facilitates efficient macromolecular structural data acquisition in fluid environments for dynamical studies.

  4. Spontaneous Tumor Lysis Syndrome

    Directory of Open Access Journals (Sweden)

    Alicia C. Weeks MD

    2015-08-01

    Full Text Available Tumor lysis syndrome (TLS is a known complication of malignancy and its treatment. The incidence varies on malignancy type, but is most common with hematologic neoplasms during cytotoxic treatment. Spontaneous TLS is thought to be rare. This case study is of a 62-year-old female admitted with multisystem organ failure, with subsequent diagnosis of aggressive B cell lymphoma. On admission, laboratory abnormalities included renal failure, elevated uric acid (20.7 mg/dL, and 3+ amorphous urates on urinalysis. Oliguric renal failure persisted despite aggressive hydration and diuretic use, requiring initiation of hemodialysis prior to chemotherapy. Antihyperuricemic therapy and hemodialysis were used to resolve hyperuricemia. However, due to multisystem organ dysfunction syndrome with extremely poor prognosis, the patient ultimately expired in the setting of a terminal ventilator wean. Although our patient did not meet current TLS criteria, she required hemodialysis due to uric acid nephropathy, a complication of TLS. This poses the clinical question of whether adequate diagnostic criteria exist for spontaneous TLS and if the lack of currently accepted guidelines has resulted in the underestimation of its incidence. Allopurinol and rasburicase are commonly used for prevention and treatment of TLS. Although both drugs decrease uric acid levels, allopurinol mechanistically prevents formation of the substrate rasburicase acts to solubilize. These drugs were administered together in our patient, although no established guidelines recommend combined use. This raises the clinical question of whether combined therapy is truly beneficial or, conversely, detrimental to patient outcomes.

  5. Spontaneous Intracranial Hypotension

    International Nuclear Information System (INIS)

    Joash, Dr.

    2015-01-01

    Epidemiology is not only rare but an important cause of new daily persistent headaches among young & middle age individuals. The Etiology & Pathogenesis is generally caused by spinal CSF leak. Precise cause remains largely unknown, underlying structural weakness of spinal meninges is suspected. There are several MR Signs of Intracranial Hypotension that include:- diffuse pachymeningeal (dural) enhancement; bilateral subdural, effusion/hematomas; Downward displacement of brain; enlargement of pituitary gland; Engorgement of dural venous sinuses; prominence of spinal epidural venous plexus and Venous sinus thrombosis & isolated cortical vein thrombosis. The sum of volumes of intracranial blood, CSF & cerebral tissue must remain constant in an intact cranium. Treatment in Many cases can be resolved spontaneously or by use Conservative approach that include bed rest, oral hydration, caffeine intake and use of abdominal binder. Imaging Modalities for Detection of CSF leakage include CT myelography, Radioisotope cisternography, MR myelography, MR imaging and Intrathecal Gd-enhanced MR

  6. Spontaneous wave packet reduction

    International Nuclear Information System (INIS)

    Ghirardi, G.C.

    1994-06-01

    There are taken into account the main conceptual difficulties met by standard quantum mechanics in dealing with physical processes involving macroscopic system. It is stressed how J.A.Wheeler's remarks and lucid analysis have been relevant to pinpoint and to bring to its extreme consequences the puzzling aspects of quantum phenomena. It is shown how the recently proposed models of spontaneous dynamical reduction represent a consistent way to overcome the conceptual difficulties of the standard theory. Obviously, many nontrivial problems remain open, the first and more relevant one being that of generalizing the model theories considered to the relativistic case. This is the challenge of the dynamical reduction program. 43 refs, 2 figs

  7. Interplay between the bacterial nucleoid protein H-NS and macromolecular crowding in compacting DNA

    NARCIS (Netherlands)

    Wintraecken, C.H.J.M.

    2012-01-01

      In this dissertation we discuss H-NS and its connection to nucleoid compaction and organization. Nucleoid formation involves a dramatic reduction in coil volume of the genomic DNA. Four factors are thought to influence coil volume: supercoiling, DNA charge neutralization, macromolecular

  8. Interplay between the bacterial nucleoid protein H-NS and macromolecular crowding in compacting DNA

    NARCIS (Netherlands)

    Wintraecken, C.H.J.M.

    2012-01-01

    In this dissertation we discuss H-NS and its connection to nucleoid compaction and organization. Nucleoid formation involves a dramatic reduction in coil volume of the genomic DNA. Four factors are thought to influence coil volume: supercoiling, DNA charge neutralization, macromolecular

  9. Detection and cellular localisation of the synthetic soluble macromolecular drug carrier pHPMA

    Czech Academy of Sciences Publication Activity Database

    Kissel, M.; Peschke, P.; Šubr, Vladimír; Ulbrich, Karel; Strunz, A. M.; Kühnlein, R.; Debus, J.; Friedrich, E.

    2002-01-01

    Roč. 29, č. 8 (2002), s. 1055-1062 ISSN 1619-7070 R&D Projects: GA ČR GV307/96/K226 Institutional research plan: CEZ:AV0Z4050913 Keywords : EPR effect * Radiolabelled macromolecules * Pharmacokinetic Subject RIV: CD - Macromolecular Chemistry Impact factor: 3.568, year: 2002

  10. MMTF-An efficient file format for the transmission, visualization, and analysis of macromolecular structures.

    Directory of Open Access Journals (Sweden)

    Anthony R Bradley

    2017-06-01

    Full Text Available Recent advances in experimental techniques have led to a rapid growth in complexity, size, and number of macromolecular structures that are made available through the Protein Data Bank. This creates a challenge for macromolecular visualization and analysis. Macromolecular structure files, such as PDB or PDBx/mmCIF files can be slow to transfer, parse, and hard to incorporate into third-party software tools. Here, we present a new binary and compressed data representation, the MacroMolecular Transmission Format, MMTF, as well as software implementations in several languages that have been developed around it, which address these issues. We describe the new format and its APIs and demonstrate that it is several times faster to parse, and about a quarter of the file size of the current standard format, PDBx/mmCIF. As a consequence of the new data representation, it is now possible to visualize structures with millions of atoms in a web browser, keep the whole PDB archive in memory or parse it within few minutes on average computers, which opens up a new way of thinking how to design and implement efficient algorithms in structural bioinformatics. The PDB archive is available in MMTF file format through web services and data that are updated on a weekly basis.

  11. Effect of macromolecular crowding on the rate of diffusion-limited ...

    Indian Academy of Sciences (India)

    The enzymatic reaction rate has been shown to be affected by the presence of such macromolecules. A simple numerical model is proposed here based on percolation and diffusion in disordered systems to study the effect of macromolecular crowding on the enzymatic reaction rates. The model qualitatively explains some ...

  12. Isolation and chemical characterization of resistant macromolecular constituents in microalgae and marine sediments

    NARCIS (Netherlands)

    Gelin, F.

    1996-01-01

    The recognition of novel, insoluble and non-hydrolysable macromolecular constituents in protective tissues of fresh-water algae and higher plants has had a major impact on our understanding of the origin and fate of sedimentary organic matter (OM) in terrestrial and lacustrine deposits. The

  13. Generation dependent mesophase behavior in extended amphiphilic dendrons in the shape of macromolecular dumbbells.

    Science.gov (United States)

    Cho, Byoung-Ki; Jain, Anurag; Gruner, Sol M; Wiesner, Ulrich

    2005-04-28

    Small angle X-ray scattering studies of 2nd and 3rd generation based extended amphiphilic dendrons in the shape of macromolecular dumbbells with identical hydrophilic volume fractions suggest 2-D hexagonal columnar and Pm3n micellar cubic mesophases, respectively, elucidating the role of shape induced interface curvature in mesophase formation.

  14. Modeling macromolecular degradation of corn starch in a twin screw extruder

    NARCIS (Netherlands)

    Einde, van den R.M.; Veen, van der M.E.; Bosman, H.; Goot, van der A.J.; Boom, R.M.

    2005-01-01

    Macromolecular degradation of starch in a twin screw extruder was modeled. A shear cell having well-defined flow conditions described earlier was used to measure peak viscosity of corn starch melts at various moisture contents and temperatures. Shear rate and elongation rate distributions in the

  15. New utilization of Polygonum multiflorum polysaccharide as macromolecular carrier of 5-fluorouracil for controlled release and immunoprotection.

    Science.gov (United States)

    Zhang, Qing; Xu, Yi; Lv, Junjiang; Cheng, Mengxia; Wu, Ying; Cao, Kun; Zhang, Xiaofeng; Mou, Xiuni; Fan, Qi

    2018-02-10

    WPMP-2 is an acid polysaccharide isolated from Polygonum multiflorum, which demonstrated excellent immunomodulatory activity. In order to reduce immunosuppression of 5-fluorouracil (5-Fu), WPMP-2 was utilized as a macromolecular carrier to conjugate the 5-Fu derivatives 5-fluorouracil-1-acetic acid (5-FUAC) through ester bond. The conjugate showed controlled drug release behaviour in vitro at 37°C in phosphate buffer (pH7.4), and only 5-FUAC was detected in the media. The cytotoxicity test in vitro showed that the conjugate exhibited different cytotoxicity to HepG-2 and HT-29 cells. In addition, immunization study in vivo illustrated that the conjugate displayed immunoprotective effect by mitigating inhibition and damage effects of 5-Fu on secretion of cytokines, proliferation of splenocytes, and phagocytosis of peritoneal macrophages. It was indicated that the conjugation of 5-Fu and WPMP-2 could be a potential double effective drug delivery system. Copyright © 2018. Published by Elsevier B.V.

  16. Spontaneous compactification to homogeneous spaces

    International Nuclear Information System (INIS)

    Mourao, J.M.

    1988-01-01

    The spontaneous compactification of extra dimensions to compact homogeneous spaces is studied. The methods developed within the framework of coset space dimensional reduction scheme and the most general form of invariant metrics are used to find solutions of spontaneous compactification equations

  17. Screening for spontaneous preterm birth

    NARCIS (Netherlands)

    van Os, M.A.; van Dam, A.J.E.M.

    2015-01-01

    Preterm birth is the most important cause of perinatal morbidity and mortality worldwide. In this thesis studies on spontaneous preterm birth are presented. The main objective was to investigate the predictive capacity of mid-trimester cervical length measurement for spontaneous preterm birth in a

  18. DUAL THEORY OF ACTION IONIZING RADIATION AND SPONTANEOUS CANCER

    Directory of Open Access Journals (Sweden)

    A. T. Gubin

    2015-01-01

    Full Text Available A mathematical model for radiogenic increasing of mortality was proposed, taking into account spontaneous background damages of the genetic material, that always occur in cells due to the influence of non-radiation internal and environmental factors. The model is based on the representation of indistinguishability between radiogenic andspontaneous cancers and on the postulates of the Kellerer-Rossi dual action theory. It was proposed that duringformation of premalignant damages dual interactions occur both between primary radiation damages, and betweenradiation and spontaneous primary damages (hybrid interactions. The role of the latter is particularly important at low levels exposure that corresponds to a linear dependence of cancer incidence on dose. Their significance is indicated by the following factor: at the adopted value of the nominal (radiation risk factor (0,05 Sv-1 and cancer mortality share among the population (0,15–0,2, the contribution of non-radiative carcinogenic factors for the total life is equivalent to radiation dose of 3–4 Sv or radiation at a constant dose rate of 40–50 mSv / year.The model assumes formation in DNA of both spaced apart (single damages with high probability of recovery, and nearby (double damages, which are more likely to interact, entering into the permanent state. Permanent damages being formed in certain portions of DNA can be inherited to daughter cells as premalignant defects. The relative role of spontaneous primary damages is greater the more single damages are formed as compared to double ones within the area of potential interaction.It was shown within this model that the presence of background cancer mortality for initial and finite population in the used by ICRP expression for interpopulation risk transfer has logical and biophysical justifications. Accounting of spontaneous primary damages and hybrid interactions enhances the capabilities for development of radiation risk models.

  19. Spontaneous Pneumomediastinum: Hamman Syndrome

    Directory of Open Access Journals (Sweden)

    Tushank Chadha, BS

    2018-04-01

    significant fat stranding. The image also showed an intraluminal stent traversing the gastric antrum and gastric pylorus with no indication of obstruction. Circumferential mural thickening of the gastric antrum and body were consistent with the patient’s history of gastric adenocarcinoma. The shotty perigastric lymph nodes with associated fat stranding, along the greater curvature of the distal gastric body suggested local regional nodal metastases and possible peritoneal carcinomatosis. The thoracic CT scans showed extensive pneumomediastinum that tracked into the soft tissues of the neck, which given the history of vomiting also raised concern for esophageal perforation. There was still no evidence of mediastinal abscess or fat stranding. Additionally, a left subclavian vein port catheter, which terminates with tip at the cavoatrial junction of the superior vena cava can also be seen on the image. Discussion: Spontaneous Pneumomediastinum, also known as Hamman syndrome, is defined by the uncommon incidence of free air in the mediastinum due to the bursting of alveoli, as a result of extended spells of shouting, coughing, or vomiting.1,2 The condition is diagnosed when a clear cause (aerodigestive rupture, barotrauma, infection secondary to gas-forming organisms3 for pneumomediastinum cannot be clearly identified on diagnostic studies. Macklin and Macklin were the first to note the pathogenesis of the syndrome and explained that the common denominator to spontaneous pneumomediastinum was that increased alveolar pressure leads to alveolar rupture.3 Common clinical findings for spontaneous pneumomediastinum include: chest pain, dyspnea, cough, and emesis.4 The condition is not always readily recognized on initial presentation in part for its rare incidence, estimated to be approximately 1 in every 44,500 ED patients3and also because of the non-specific presenting symptoms. For this patient, there was no clear singular cause, and therefore she received care for spontaneous

  20. Spontaneous breaking of supersymmetry

    Energy Technology Data Exchange (ETDEWEB)

    Zumino, B.

    1981-12-01

    There has been recently a revival of interest in supersymmetric gauge theories, stimulated by the hope that supersymmetry might help in clarifying some of the questions which remain unanswered in the so called Grand Unified Theories and in particular the gauge hierarchy problem. In a Grand Unified Theory one has two widely different mass scales: the unification mass M approx. = 10/sup 15/GeV at which the unification group (e.g. SU(5)) breaks down to SU(3) x SU(2) x U(1) and the mass ..mu.. approx. = 100 GeV at which SU(2) x U(1) is broken down to the U(1) of electromagnetism. There is at present no theoretical understanding of the extreme smallness of the ratio ..mu../M of these two numbers. This is the gauge hierarchy problem. This lecture attempts to review the various mechanisms for spontaneous supersymmetry breaking in gauge theories. Most of the discussions are concerned with the tree approximation, but what is presently known about radiative correction is also reviewed.

  1. Spontaneous intracranial hypotension

    International Nuclear Information System (INIS)

    Haritanti, A.; Karacostas, D.; Drevelengas, A.; Kanellopoulos, V.; Paraskevopoulou, E.; Lefkopoulos, A.; Economou, I.; Dimitriadis, A.S.

    2009-01-01

    Spontaneous intracranial hypotension (SIH) is an uncommon but increasingly recognized syndrome. Orthostatic headache with typical findings on magnetic resonance imaging (MRI) are the key to diagnosis. Delayed diagnosis of this condition may subject patients to unnecessary procedures and prolong morbidity. We describe six patients with SIH and outline the important clinical and neuroimaging findings. They were all relatively young, 20-54 years old, with clearly orthostatic headache, minimal neurological signs (only abducent nerve paresis in two) and diffuse pachymeningeal gadolinium enhancement on brain MRI, while two of them presented subdural hygromas. Spinal MRI was helpful in detecting a cervical cerebrospinal fluid leak in three patients and dilatation of the vertebral venous plexus with extradural fluid collection in another. Conservative management resulted in rapid resolution of symptoms in five patients (10 days-3 weeks) and in one who developed cerebral venous sinus thrombosis, the condition resolved in 2 months. However, this rapid clinical improvement was not accompanied by an analogous regression of the brain MR findings that persisted on a longer follow-up. Along with recent literature data, our patients further point out that SIH, to be correctly diagnosed, necessitates increased alertness by the attending physician, in the evaluation of headaches

  2. Spontaneous lateral temporal encephalocele.

    Science.gov (United States)

    Tuncbilek, Gokhan; Calis, Mert; Akalan, Nejat

    2013-01-01

    A spontaneous encephalocele is one that develops either because of embryological maldevelopment or from a poorly understood postnatal process that permits brain herniation to occur. We here report a rare case of lateral temporal encephalocele extending to the infratemporal fossa under the zygomatic arch. At birth, the infant was noted to have a large cystic mass in the right side of the face. After being operated on initially in another center in the newborn period, the patient was referred to our clinic with a diagnosis of temporal encephalocele. He was 6 months old at the time of admission. Computerized tomography scan and magnetic resonance imaging studies revealed a 8 × 9 cm fluid-filled, multiloculated cystic mass at the right infratemporal fossa. No intracranial pathology or connection is seen. The patient was operated on to reduce the distortion effect of the growing mass. The histopathological examination of the sac revealed well-differentiated mature glial tissue stained with glial fibrillary acid protein. This rare clinical presentation of encephaloceles should be taken into consideration during the evaluation of the lateral facial masses in the infancy period, and possible intracranial connection should be ruled out before surgery to avoid complications.

  3. Ceruloplasmin: Macromolecular Assemblies with Iron-Containing Acute Phase Proteins

    Science.gov (United States)

    Samygina, Valeriya R.; Sokolov, Alexey V.; Bourenkov, Gleb; Petoukhov, Maxim V.; Pulina, Maria O.; Zakharova, Elena T.; Vasilyev, Vadim B.; Bartunik, Hans; Svergun, Dmitri I.

    2013-01-01

    Copper-containing ferroxidase ceruloplasmin (Cp) forms binary and ternary complexes with cationic proteins lactoferrin (Lf) and myeloperoxidase (Mpo) during inflammation. We present an X-ray crystal structure of a 2Cp-Mpo complex at 4.7 Å resolution. This structure allows one to identify major protein–protein interaction areas and provides an explanation for a competitive inhibition of Mpo by Cp and for the activation of p-phenylenediamine oxidation by Mpo. Small angle X-ray scattering was employed to construct low-resolution models of the Cp-Lf complex and, for the first time, of the ternary 2Cp-2Lf-Mpo complex in solution. The SAXS-based model of Cp-Lf supports the predicted 1∶1 stoichiometry of the complex and demonstrates that both lobes of Lf contact domains 1 and 6 of Cp. The 2Cp-2Lf-Mpo SAXS model reveals the absence of interaction between Mpo and Lf in the ternary complex, so Cp can serve as a mediator of protein interactions in complex architecture. Mpo protects antioxidant properties of Cp by isolating its sensitive loop from proteases. The latter is important for incorporation of Fe3+ into Lf, which activates ferroxidase activity of Cp and precludes oxidation of Cp substrates. Our models provide the structural basis for possible regulatory role of these complexes in preventing iron-induced oxidative damage. PMID:23843990

  4. Heat Damaged Forages: Effects on Forage Quality

    Science.gov (United States)

    Traditionally, heat damage in forages has been associated with alterations in forage protein quality as a result of Maillard reactions, and most producers and nutritionists are familiar with this concept. However, this is not necessarily the most important negative consequence of spontaneous heating...

  5. Bilateral spontaneous carotid artery dissection.

    Science.gov (United States)

    Townend, Bradley Scott; Traves, Laura; Crimmins, Denis

    2005-06-01

    Bilateral internal carotid artery dissections have been reported, but spontaneous bilateral dissections are rare. Internal carotid artery dissection can present with a spectrum of symptoms ranging from headache to completed stroke. Two cases of spontaneous bilateral carotid artery dissection are presented, one with headache and minimal symptoms and the other with a stroke syndrome. No cause could be found in either case, making the dissections completely spontaneous. Bilateral internal carotid artery dissection (ICAD) should be considered in young patients with unexplained head and neck pain with or without focal neurological symptoms and signs. The increasing availability of imaging would sustain the higher index of suspicion.

  6. Room-temperature macromolecular serial crystallography using synchrotron radiation

    Directory of Open Access Journals (Sweden)

    Francesco Stellato

    2014-07-01

    Full Text Available A new approach for collecting data from many hundreds of thousands of microcrystals using X-ray pulses from a free-electron laser has recently been developed. Referred to as serial crystallography, diffraction patterns are recorded at a constant rate as a suspension of protein crystals flows across the path of an X-ray beam. Events that by chance contain single-crystal diffraction patterns are retained, then indexed and merged to form a three-dimensional set of reflection intensities for structure determination. This approach relies upon several innovations: an intense X-ray beam; a fast detector system; a means to rapidly flow a suspension of crystals across the X-ray beam; and the computational infrastructure to process the large volume of data. Originally conceived for radiation-damage-free measurements with ultrafast X-ray pulses, the same methods can be employed with synchrotron radiation. As in powder diffraction, the averaging of thousands of observations per Bragg peak may improve the ratio of signal to noise of low-dose exposures. Here, it is shown that this paradigm can be implemented for room-temperature data collection using synchrotron radiation and exposure times of less than 3 ms. Using lysozyme microcrystals as a model system, over 40 000 single-crystal diffraction patterns were obtained and merged to produce a structural model that could be refined to 2.1 Å resolution. The resulting electron density is in excellent agreement with that obtained using standard X-ray data collection techniques. With further improvements the method is well suited for even shorter exposures at future and upgraded synchrotron radiation facilities that may deliver beams with 1000 times higher brightness than they currently produce.

  7. Spontaneous intraorbital hematoma: case report

    Directory of Open Access Journals (Sweden)

    Vinodan Paramanathan

    2010-12-01

    Full Text Available Vinodan Paramanathan, Ardalan ZolnourianQueen's Hospital NHS Foundation Trust, Burton on Trent, Staffordshire DE13 0RB, UKAbstract: Spontaneous intraorbital hematoma is an uncommon clinical entity seen in ophthalmology practice. It is poorly represented in the literature. Current evidence attributes it to orbital trauma, neoplasm, vascular malformations, acute sinusitis, and systemic abnormalities. A 65-year-old female presented with spontaneous intraorbital hematoma manifesting as severe ocular pains, eyelid edema, proptosis, and diplopia, without a history of trauma. Computer tomography demonstrated a fairly well defined extraconal lesion with opacification of the paranasal sinuses. The principal differential based on all findings was that of a spreading sinus infection and an extraconal tumor. An unprecedented finding of a spontaneous orbital hematoma was discovered when the patient was taken to theater. We discuss the rarity of this condition and its management.Keywords: hemorrhage, ophthalmology, spontaneous, intra-orbital, hematoma

  8. Radiation damage

    CERN Document Server

    Heijne, Erik H M; CERN. Geneva

    1998-01-01

    a) Radiation damage in organic materials. This series of lectures will give an overview of radiation effects on materials and components frequently used in accelerator engineering and experiments. Basic degradation phenomena will be presented for organic materials with comprehensive damage threshold doses for commonly used rubbers, thermoplastics, thermosets and composite materials. Some indications will be given for glass, scintillators and optical fibres. b) Radiation effects in semiconductor materials and devices. The major part of the time will be devoted to treat radiation effects in semiconductor sensors and the associated electronics, in particular displacement damage, interface and single event phenomena. Evaluation methods and practical aspects will be shown. Strategies will be developed for the survival of the materials under the expected environmental conditions of the LHC machine and detectors. I will describe profound revolution in our understanding of black holes and their relation to quantum me...

  9. Spontaneous ischaemic stroke in dogs

    DEFF Research Database (Denmark)

    Gredal, Hanne Birgit; Skerritt, G. C.; Gideon, P.

    2013-01-01

    Translation of experimental stroke research into the clinical setting is often unsuccessful. Novel approaches are therefore desirable. As humans, pet dogs suffer from spontaneous ischaemic stroke and may hence offer new ways of studying genuine stroke injury mechanisms.......Translation of experimental stroke research into the clinical setting is often unsuccessful. Novel approaches are therefore desirable. As humans, pet dogs suffer from spontaneous ischaemic stroke and may hence offer new ways of studying genuine stroke injury mechanisms....

  10. Spontaneity and international marketing performance

    OpenAIRE

    Souchon, Anne L.; Hughes, Paul; Farrell, Andrew M.; Nemkova, Ekaterina; Oliveira, Joao S.

    2016-01-01

    The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link. Purpose – The purpose of this paper is to ascertain how today’s international marketers can perform better on the global scene by harnessing spontaneity. Design/methodology/approach – The authors draw on contingency theory to develop a model of the spontaneity – international marketing performance relationship, and identify three potential m...

  11. Local analysis of strains and rotations for macromolecular electron microscopy maps

    Energy Technology Data Exchange (ETDEWEB)

    Martin-Ramos, A.; Prieto, F.; Melero, R.; Martin-Benito, J.; Jonic, S.; Navas-Calvente, J.; Vargas, J.; Oton, J.; Abrishami, V.; Rosa-Trevin, J.L. de la; Gomez-Blanco, J.; Vilas, J.L.; Marabini, R.; Carazo, R.; Sorzano, C.O.S.

    2016-07-01

    Macromolecular complexes can be considered as molecular nano-machines that must have mobile parts in order to perform their physiological functions. The reordering of their parts is essential to execute their task. These rearrangements induce local strains and rotations which, after analyzing them, may provide relevant information about how the proteins perform their function. In this project these deformations of the macromolecular complexes are characterized, translating into a “mathematical language” the conformational changes of the complexes when they perform their function. Electron Microscopy (EM) volumes are analyzed using a method that uses B-splines as its basis functions. It is shown that the results obtained are consistent with the conformational changes described in their corresponding reference publications. (Author)

  12. From “Simple” DNA-Protein Interactions to the Macromolecular Machines of Gene Expression

    Science.gov (United States)

    von Hippel, Peter H.

    2008-01-01

    The physicochemical concepts that underlie our present ideas on the structure and assembly of the “macromolecular machines of gene expression” are developed, starting with the structure and folding of the individual protein and DNA components, the thermodynamics and kinetics of their conformational rearrangements during complex assembly, and the molecular basis of the sequence specificity and recognition interactions of the final assemblies that include the DNA genome. The role of diffusion in reduced dimensions in the kinetics of the assembly of macromolecular machines from their components is also considered, and diffusion-driven reactions are compared with those fueled by ATP binding and hydrolysis, as well as by the specific covalent chemical modifications involved in rearranging chromatin and modifying signal transduction networks in higher organisms. PMID:17477836

  13. From "simple" DNA-protein interactions to the macromolecular machines of gene expression.

    Science.gov (United States)

    von Hippel, Peter H

    2007-01-01

    The physicochemical concepts that underlie our present ideas on the structure and assembly of the "macromolecular machines of gene expression" are developed, starting with the structure and folding of the individual protein and DNA components, the thermodynamics and kinetics of their conformational rearrangements during complex assembly, and the molecular basis of the sequence specificity and recognition interactions of the final assemblies that include the DNA genome. The role of diffusion in reduced dimensions in the kinetics of the assembly of macromolecular machines from their components is also considered, and diffusion-driven reactions are compared with those fueled by ATP binding and hydrolysis, as well as by the specific covalent chemical modifications involved in rearranging chromatin and modifying signal transduction networks in higher organisms.

  14. Long-Wavelength X-Ray Diffraction and Its Applications in Macromolecular Crystallography.

    Science.gov (United States)

    Weiss, Manfred S

    2017-01-01

    For many years, diffraction experiments in macromolecular crystallography at X-ray wavelengths longer than that of Cu-K α (1.54 Å) have been largely underappreciated. Effects caused by increased X-ray absorption result in the fact that these experiments are more difficult than the standard diffraction experiments at short wavelengths. However, due to the also increased anomalous scattering of many biologically relevant atoms, important additional structural information can be obtained. This information, in turn, can be used for phase determination, for substructure identification, in molecular replacement approaches, as well as in structure refinement. This chapter reviews the possibilities and the difficulties associated with such experiments, and it provides a short description of two macromolecular crystallography synchrotron beam lines dedicated to long-wavelength X-ray diffraction experiments.

  15. Romp: The Method of Choice for Precise Macromolecular Engineering and Synthesis of Smart Materials

    Science.gov (United States)

    Khosravi, Ezat; Castle, Thomas C.; Kujawa, Margaret; Leejarkpai, Jan; Hutchings, Lian R.; Hine, Peter J.

    The recent advances in olefin metathesis highlight the impact of Ring Opening Metathesis Polymerisation (ROMP) as a powerful technique for macromolecular engineering and synthesis of smart materials with well-defined structures. ROMP has attracted a considerable research attention recently particularly by industry largely due to the development of well-defined metal complexes as initiators and also because of the award of the Noble Prize for Chemistry in 2005 to three scientists (Chauvin, Grubbs, Schrock) for their contributions in this area. This chapter discusses several interesting examples in order to demonstrate that ROMP is a power tool in macromolecular engineering and that it allows the design and synthesis of polymers with novel topologies.

  16. Refinement of macromolecular structures against neutron data withSHELXL2013.

    Science.gov (United States)

    Gruene, Tim; Hahn, Hinrich W; Luebben, Anna V; Meilleur, Flora; Sheldrick, George M

    2014-02-01

    Some of the improvements in SHELX2013 make SHELXL convenient to use for refinement of macromolecular structures against neutron data without the support of X-ray data. The new NEUT instruction adjusts the behaviour of the SFAC instruction as well as the default bond lengths of the AFIX instructions. This work presents a protocol on how to use SHELXL for refinement of protein structures against neutron data. It includes restraints extending the Engh & Huber [ Acta Cryst. (1991), A 47 , 392-400] restraints to H atoms and discusses several of the features of SHELXL that make the program particularly useful for the investigation of H atoms with neutron diffraction. SHELXL2013 is already adequate for the refinement of small molecules against neutron data, but there is still room for improvement, like the introduction of chain IDs for the refinement of macromolecular structures.

  17. The R-factor gap in macromolecular crystallography: an untapped potential for insights on accurate structures.

    Science.gov (United States)

    Holton, James M; Classen, Scott; Frankel, Kenneth A; Tainer, John A

    2014-09-01

    In macromolecular crystallography, the agreement between observed and predicted structure factors (Rcryst and Rfree ) is seldom better than 20%. This is much larger than the estimate of experimental error (Rmerge ). The difference between Rcryst and Rmerge is the R-factor gap. There is no such gap in small-molecule crystallography, for which calculated structure factors are generally considered more accurate than the experimental measurements. Perhaps the true noise level of macromolecular data is higher than expected? Or is the gap caused by inaccurate phases that trap refined models in local minima? By generating simulated diffraction patterns using the program MLFSOM, and including every conceivable source of experimental error, we show that neither is the case. Processing our simulated data yielded values that were indistinguishable from those of real data for all crystallographic statistics except the final Rcryst and Rfree . These values decreased to 3.8% and 5.5% for simulated data, suggesting that the reason for high R-factors in macromolecular crystallography is neither experimental error nor phase bias, but rather an underlying inadequacy in the models used to explain our observations. The present inability to accurately represent the entire macromolecule with both its flexibility and its protein-solvent interface may be improved by synergies between small-angle X-ray scattering, computational chemistry and crystallography. The exciting implication of our finding is that macromolecular data contain substantial hidden and untapped potential to resolve ambiguities in the true nature of the nanoscale, a task that the second century of crystallography promises to fulfill. Coordinates and structure factors for the real data have been submitted to the Protein Data Bank under accession 4tws. © 2014 The Authors. FEBS Journal published by John Wiley & Sons Ltd on behalf of FEBS.

  18. Synthetic Macromolecular Antibiotic Platform for Inhalable Therapy against Aerosolized Intracellular Alveolar Infections.

    Science.gov (United States)

    Das, Debobrato; Chen, Jasmin; Srinivasan, Selvi; Kelly, Abby M; Lee, Brian; Son, Hye-Nam; Radella, Frank; West, T Eoin; Ratner, Daniel M; Convertine, Anthony J; Skerrett, Shawn J; Stayton, Patrick S

    2017-06-05

    Lung-based intracellular bacterial infections remain one of the most challenging infectious disease settings. For example, the current standard for treating Franciscella tularensis pneumonia (tularemia) relies on administration of oral or intravenous antibiotics that poorly achieve and sustain pulmonary drug bioavailability. Inhalable antibiotic formulations are approved and in clinical development for upper respiratory infections, but sustained drug dosing from inhaled antibiotics against alveolar intracellular infections remains a current unmet need. To provide an extended therapy against alveolar intracellular infections, we have developed a macromolecular therapeutic platform that provides sustained local delivery of ciprofloxacin with controlled dosing profiles. Synthesized using RAFT polymerization, these macromolecular prodrugs characteristically have high drug loading (16-17 wt % drug), tunable hydrolysis kinetics mediated by drug linkage chemistry (slow-releasing alkyllic vs fast-releasing phenolic esters), and, in general, represent new fully synthetic nanotherapeutics with streamlined manufacturing profiles. In aerosolized and completely lethal F.t. novicida mouse challenge models, the fast-releasing ciprofloxacin macromolecular prodrug provided high cure efficiencies (75% survival rate under therapeutic treatment), and the importance of release kinetics was demonstrated by the inactivity of the similar but slow-releasing prodrug system. Pharmacokinetics and biodistribution studies further demonstrated that the efficacious fast-releasing prodrug retained drug dosing in the lung above the MIC over a 48 h period with corresponding C max /MIC and AUC 0-24h /MIC ratios being greater than 10 and 125, respectively; the thresholds for optimal bactericidal efficacy. These findings identify the macromolecular prodrug platform as a potential therapeutic system to better treat alveolar intracellular infections such as F. tularensis, where positive patient outcomes

  19. Macromolecular X-ray structure determination using weak, single-wavelength anomalous data

    Energy Technology Data Exchange (ETDEWEB)

    Bunkóczi, Gábor; McCoy, Airlie J.; Echols, Nathaniel; Grosse-Kunstleve, Ralf W.; Adams, Paul D.; Holton, James M.; Read, Randy J.; Terwilliger, Thomas C.

    2014-12-22

    We describe a likelihood-based method for determining the substructure of anomalously scattering atoms in macromolecular crystals that allows successful structure determination by single-wavelength anomalous diffraction (SAD) X-ray analysis with weak anomalous signal. With the use of partial models and electron density maps in searches for anomalously scattering atoms, testing of alternative values of parameters and parallelized automated model-building, this method has the potential to extend the applicability of the SAD method in challenging cases.

  20. Facilitating structure determination: workshop on robotics and automation in macromolecular crystallography

    International Nuclear Information System (INIS)

    Ralston, Corie; Cork, C.W.; McDermott, G.; Earnest, T.N.

    2006-01-01

    As part of the annual Advanced Light Source (ALS) and Stanford Synchrotron Radiation Laboratory (SSRL) Users' Meeting in October of this year, the macromolecular crystallography staff at both synchrotrons held a joint hands-on workshop to address automation issues in crystal mounting and data collection at the beamline. This paper describes the ALS portion of the workshop, while the accompanying paper reviews the SSRL workshop

  1. Measurement and Interpretation of Diffuse Scattering in X-Ray Diffraction for Macromolecular Crystallography

    Energy Technology Data Exchange (ETDEWEB)

    Wall, Michael E. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2017-10-16

    X-ray diffraction from macromolecular crystals includes both sharply peaked Bragg reflections and diffuse intensity between the peaks. The information in Bragg scattering reflects the mean electron density in the unit cells of the crystal. The diffuse scattering arises from correlations in the variations of electron density that may occur from one unit cell to another, and therefore contains information about collective motions in proteins.

  2. Definitions of terms relating to individual macromolecules, macromolecular assemblies, polymer solutions, and amorphous bulk polymers (IUPAC Recommendations 2014)

    Czech Academy of Sciences Publication Activity Database

    Stepto, R.; Chang, T.; Kratochvíl, Pavel; Hess, M.; Horie, K.; Sato, T.; Vohlídal, J.

    2015-01-01

    Roč. 87, č. 1 (2015), s. 71-120 ISSN 0033-4545 Institutional support: RVO:61389013 Keywords : amorphous polymers * bulk polymers * IUPAC Polymer Division Subject RIV: CD - Macromolecular Chemistry Impact factor: 2.615, year: 2015

  3. Macromolecular diffusion in crowded media beyond the hard-sphere model.

    Science.gov (United States)

    Blanco, Pablo M; Garcés, Josep Lluís; Madurga, Sergio; Mas, Francesc

    2018-04-25

    The effect of macromolecular crowding on diffusion beyond the hard-core sphere model is studied. A new coarse-grained model is presented, the Chain Entanglement Softened Potential (CESP) model, which takes into account the macromolecular flexibility and chain entanglement. The CESP model uses a shoulder-shaped interaction potential that is implemented in the Brownian Dynamics (BD) computations. The interaction potential contains only one parameter associated with the chain entanglement energetic cost (Ur). The hydrodynamic interactions are included in the BD computations via Tokuyama mean-field equations. The model is used to analyze the diffusion of a streptavidin protein among different sized dextran obstacles. For this system, Ur is obtained by fitting the streptavidin experimental long-time diffusion coefficient Dlongversus the macromolecular concentration for D50 (indicating their molecular weight in kg mol-1) dextran obstacles. The obtained Dlong values show better quantitative agreement with experiments than those obtained with hard-core spheres. Moreover, once parametrized, the CESP model is also able to quantitatively predict Dlong and the anomalous exponent (α) for streptavidin diffusion among D10, D400 and D700 dextran obstacles. Dlong, the short-time diffusion coefficient (Dshort) and α are obtained from the BD simulations by using a new empirical expression, able to describe the full temporal evolution of the diffusion coefficient.

  4. A Sensitized Emission Based Calibration of FRET Efficiency for Probing the Architecture of Macromolecular Machines.

    Science.gov (United States)

    Joglekar, Ajit; Chen, Renjie; Lawrimore, Joshua

    2013-01-01

    Macromolecular machines participate in almost every cell biological function. These machines can take the form of well-defined protein structures such as the kinetochore, or more loosely organized protein assemblies like the endocytic coat. The protein architecture of these machines-the arrangement of multiple copies of protein subunits at the nanoscale, is necessary for understanding their cell biological function and biophysical mechanism. Defining this architecture in vivo presents a major challenge. High density of protein molecules within macromolecular machines severely limits the effectiveness of super-resolution microscopy. However, this density is ideal for Forster Resonance Energy Transfer (FRET), which can determine the proximity between neighboring molecules. Here, we present a simple FRET quantitation scheme that calibrates a standard epifluorescence microscope for measuring donor-acceptor separations. This calibration can be used to deduce FRET efficiency fluorescence intensity measurements. This method will allow accurate determination of FRET efficiency over a wide range of values and FRET pair number. It will also allow dynamic FRET measurements with high spatiotemporal resolution under cell biological conditions. Although the poor maturation efficiency of genetically encoded fluorescent proteins presents a challenge, we show that its effects can be alleviated. To demonstrate this methodology, we probe the in vivo architecture of the γ-Tubulin Ring. Our technique can be applied to study the architecture and dynamics of a wide range of macromolecular machines.

  5. Protein crystallography for aspiring crystallographers or how to avoid pitfalls and traps in macromolecular structure determination.

    Science.gov (United States)

    Wlodawer, Alexander; Minor, Wladek; Dauter, Zbigniew; Jaskolski, Mariusz

    2013-11-01

    The number of macromolecular structures deposited in the Protein Data Bank now approaches 100,000, with the vast majority of them determined by crystallographic methods. Thousands of papers describing such structures have been published in the scientific literature, and 20 Nobel Prizes in chemistry or medicine have been awarded for discoveries based on macromolecular crystallography. New hardware and software tools have made crystallography appear to be an almost routine (but still far from being analytical) technique and many structures are now being determined by scientists with very limited experience in the practical aspects of the field. However, this apparent ease is sometimes illusory and proper procedures need to be followed to maintain high standards of structure quality. In addition, many noncrystallographers may have problems with the critical evaluation and interpretation of structural results published in the scientific literature. The present review provides an outline of the technical aspects of crystallography for less experienced practitioners, as well as information that might be useful for users of macromolecular structures, aiming to show them how to interpret (but not overinterpret) the information present in the coordinate files and in their description. A discussion of the extent of information that can be gleaned from the atomic coordinates of structures solved at different resolution is provided, as well as problems and pitfalls encountered in structure determination and interpretation. © 2013 FEBS.

  6. In Vitro and In Vivo Evaluation of Microparticulate Drug Delivery Systems Composed of Macromolecular Prodrugs

    Directory of Open Access Journals (Sweden)

    Yoshiharu Machida

    2008-08-01

    Full Text Available Macromolecular prodrugs are very useful systems for achieving controlled drug release and drug targeting. In particular, various macromolecule-antitumor drug conjugates enhance the effectiveness and improve the toxic side effects. Also, polymeric micro- and nanoparticles have been actively examined and their in vivo behaviors elucidated, and it has been realized that their particle characteristics are very useful to control drug behavior. Recently, researches based on the combination of the concepts of macromolecular prodrugs and micro- or nanoparticles have been reported, although they are limited. Macromolecular prodrugs enable drugs to be released at a certain controlled release rate based on the features of the macromolecule-drug linkage. Micro- and nanoparticles can control in vivo behavior based on their size, surface charge and surface structure. These merits are expected for systems produced by the combination of each concept. In this review, several micro- or nanoparticles composed of macromolecule-drug conjugates are described for their preparation, in vitro properties and/or in vivo behavior.

  7. Fundamental and biotechnological applications of neutron scattering measurements for macromolecular dynamics.

    Science.gov (United States)

    Tehei, Moeava; Daniel, Roy; Zaccai, Giuseppe

    2006-09-01

    To explore macromolecular dynamics on the picosecond timescale, we used neutron spectroscopy. First, molecular dynamics were analyzed for the hyperthermophile malate dehydrogenase from Methanococcus jannaschii and a mesophilic homologue, the lactate dehydrogenase from Oryctolagus cunniculus muscle. Hyperthermophiles have elaborate molecular mechanisms of adaptation to extremely high temperature. Using a novel elastic neutron scattering approach that provides independent measurements of the global flexibility and of the structural resilience (rigidity), we have demonstrated that macromolecular dynamics represents one of these molecular mechanisms of thermoadaptation. The flexibilities were found to be similar for both enzymes at their optimal activity temperature and the resilience is higher for the hyperthermophilic protein. Secondly, macromolecular motions were examined in a native and immobilized dihydrofolate reductase (DHFR) from Escherichia coli. The immobilized mesophilic enzyme has increased stability and decreased activity, so that its properties are changed to resemble those of the thermophilic enzyme. Are these changes reflected in dynamical behavior? For this study, we performed quasielastic neutron scattering measurements to probe the protein motions. The residence time is 7.95 ps for the native DHFR and 20.36 ps for the immobilized DHFR. The average height of the potential barrier to local motions is therefore increased in the immobilized DHFR, with a difference in activation energy equal to 0.54 kcal/mol, which is, using the theoretical rate equation, of the same order than expected from calculation.

  8. Tuning the properties of an anthracene-based PPE-PPV copolymer by fine variation of its macromolecular parameters

    Czech Academy of Sciences Publication Activity Database

    Tinti, F.; Sabir, F. K.; Gazzano, M.; Righi, S.; Ulbricht, C.; Usluer, Ö.; Pokorná, Veronika; Cimrová, Věra; Yohannes, T.; Egbe, D. A. M.; Camaioni, N.

    2013-01-01

    Roč. 3, č. 19 (2013), s. 6972-6980 ISSN 2046-2069 R&D Projects: GA ČR GAP106/12/0827; GA ČR(CZ) GA13-26542S Institutional support: RVO:61389013 Keywords : anthracene-containing PPE-PPV copolymer * macromolecular parameters * structural and transport properties Subject RIV: CD - Macromolecular Chemistry Impact factor: 3.708, year: 2013

  9. Tort Damages

    NARCIS (Netherlands)

    L.T. Visscher (Louis)

    2008-01-01

    textabstractAbstract: In this Chapter, I provide an overview of Law and Economics literature regarding tort damages. Where necessary, attention is also spent to rules of tort liability. Both types of rules provide behavioral incentives to both injurers and victims, with respect to their level of

  10. Gaussian-Based Smooth Dielectric Function: A Surface-Free Approach for Modeling Macromolecular Binding in Solvents

    Directory of Open Access Journals (Sweden)

    Arghya Chakravorty

    2018-03-01

    Full Text Available Conventional modeling techniques to model macromolecular solvation and its effect on binding in the framework of Poisson-Boltzmann based implicit solvent models make use of a geometrically defined surface to depict the separation of macromolecular interior (low dielectric constant from the solvent phase (high dielectric constant. Though this simplification saves time and computational resources without significantly compromising the accuracy of free energy calculations, it bypasses some of the key physio-chemical properties of the solute-solvent interface, e.g., the altered flexibility of water molecules and that of side chains at the interface, which results in dielectric properties different from both bulk water and macromolecular interior, respectively. Here we present a Gaussian-based smooth dielectric model, an inhomogeneous dielectric distribution model that mimics the effect of macromolecular flexibility and captures the altered properties of surface bound water molecules. Thus, the model delivers a smooth transition of dielectric properties from the macromolecular interior to the solvent phase, eliminating any unphysical surface separating the two phases. Using various examples of macromolecular binding, we demonstrate its utility and illustrate the comparison with the conventional 2-dielectric model. We also showcase some additional abilities of this model, viz. to account for the effect of electrolytes in the solution and to render the distribution profile of water across a lipid membrane.

  11. The effect of macromolecular crowding on the structure of the protein complex superoxide dismutase

    Science.gov (United States)

    Rajapaksha Mudalige, Ajith Rathnaweera

    Biological environments contain between 7 - 40% macromolecules by volume. This reduces the available volume for macromolecules and elevates the osmotic pressure relative to pure water. Consequently, biological macromolecules in their native environments tend to adopt more compact and dehydrated conformations than those in vitro. This effect is referred to as macromolecular crowding and constitutes an important physical difference between native biological environments and the simple solutions in which biomolecules are usually studied. We used small angle scattering (SAS) to measure the effects of macromolecular crowding on the size of a protein complex, superoxide dismutase (SOD). Crowding was induced using 400 MW polyethylene glycol (PEG), triethylene glycol (TEG), methyl-alpha-glucoside (alpha-MG) and trimethylamine N-oxide (TMAO). Parallel small angle neutron scattering (SANS) and small angle X-ray scattering (SAXS) allowed us to unambiguously attribute apparent changes in radius of gyration to changes in the structure of SOD. For a 40% PEG solution, we find that the volume of SOD was reduced by 9%. SAS coupled with osmotic pressure measurements allowed us to estimate a compressibility modulus for SOD. We believe this to be the first time the osmotic compressibility of a protein complex was measured. Molecular Dynamics (MD) simulations are widely used to obtain insights on biomolecular processes. However, it is not clear whether MD is capable of predicting subtle effects of macromolecular crowding. We used our experimentally observed compressibility of SOD to evaluate the ability of MD to predict macromolecular crowding. Effects of macromolecular crowding due to PEG on SOD were modeled using an all atom MD simulation with the CHARMM forcefield and the crystallographically resolved structures of SOD and PEG. Two parallel MD simulations were performed for SOD in water and SOD in 40% PEG for over 150~ns. Over the period of the simulation the SOD structure in 40

  12. A case of spontaneous ventriculocisternostomy

    International Nuclear Information System (INIS)

    Yamane, Kanji; Yoshimoto, Hisanori; Harada, Kiyoshi; Uozumi, Tohru; Kuwabara, Satoshi.

    1983-01-01

    The authors experienced a case of spontaneous ventriculocisternostomy diagnosed by CT scan with metrizamide and Conray. Patient was 23-year-old male who had been in good health until one month before admission, when he began to have headache and tinnitus. He noticed bilateral visual acuity was decreased about one week before admission and vomiting appeared two days before admission. He was admitted to our hospital because of bilateral papilledema and remarkable hydrocephalus diagnosed by CT scan. On admission, no abnormal neurological signs except for bilateral papilledema were noted. Immediately, right ventricular drainage was performed. Pressure of the ventricle was over 300mmH 2 O and CSF was clear. PVG and PEG disclosed an another cavity behind the third ventricle, which was communicated with the third ventricle, and occlusion of aqueduct of Sylvius. Metrizamide CT scan and Conray CT scan showed a communication between this cavity and quadrigeminal and supracerebellar cisterns. On these neuroradiological findings, the diagnosis of obstructive hydrocephalus due to benign aqueduct stenosis accompanied with spontaneous ventriculocisternostomy was obtained. Spontaneous ventriculocisternostomy was noticed to produce arrest of hydrocephalus, but with our case, spontaneous regression of such symptoms did not appeared. By surgical ventriculocisternostomy (method by Torkildsen, Dandy, or Scarff), arrest of hydrocephalus was seen in about 50 to 70 per cent, which was the same results as those of spontaneous ventriculocisternostomy. It is concluded that VP shunt or VA shunt is thought to be better treatment of obstructive hydrocephalus than the various kinds of surgical ventriculocisternostomy. (J.P.N.)

  13. Optical antenna enhanced spontaneous emission.

    Science.gov (United States)

    Eggleston, Michael S; Messer, Kevin; Zhang, Liming; Yablonovitch, Eli; Wu, Ming C

    2015-02-10

    Atoms and molecules are too small to act as efficient antennas for their own emission wavelengths. By providing an external optical antenna, the balance can be shifted; spontaneous emission could become faster than stimulated emission, which is handicapped by practically achievable pump intensities. In our experiments, InGaAsP nanorods emitting at ∼ 200 THz optical frequency show a spontaneous emission intensity enhancement of 35 × corresponding to a spontaneous emission rate speedup ∼ 115 ×, for antenna gap spacing, d = 40 nm. Classical antenna theory predicts ∼ 2,500 × spontaneous emission speedup at d ∼ 10 nm, proportional to 1/d(2). Unfortunately, at d antenna efficiency drops below 50%, owing to optical spreading resistance, exacerbated by the anomalous skin effect (electron surface collisions). Quantum dipole oscillations in the emitter excited state produce an optical ac equivalent circuit current, I(o) = qω|x(o)|/d, feeding the antenna-enhanced spontaneous emission, where q|x(o)| is the dipole matrix element. Despite the quantum-mechanical origin of the drive current, antenna theory makes no reference to the Purcell effect nor to local density of states models. Moreover, plasmonic effects are minor at 200 THz, producing only a small shift of antenna resonance frequency.

  14. Spontaneous subcapsular and perirrenal hemorrhage

    International Nuclear Information System (INIS)

    Fuster, M.J.; Saez, J.; Perez-Paya, F.J.; Fernandez, F.

    1997-01-01

    To assess the role of CT in the etiologic diagnosis of spontaneous subcapsular and perirrenal hemorrhage. The CT findings are described in 13 patients presenting subcapsular and perirrenal hemorrhage. Those patients in whom the bleeding was not spontaneous were excluded. Surgical confirmation was obtained in nine cases. In 11 of the 13 cases (84.6%), involving five adenocarcinomas, five angiomyolipoma, two complicated cysts and one case of panarterities nodosa, CT disclosed the underlying pathology. In two cases (15.4%), it only revealed the extension of the hematoma, but gave no clue to its origin. CT is the technique of choice when spontaneous subcapsular and perirrenal hemorrhage is suspected since, in most cases, it reveals the underlying pathology. (Author)

  15. Spontaneous waves in muscle fibres

    Energy Technology Data Exchange (ETDEWEB)

    Guenther, Stefan; Kruse, Karsten [Department of Theoretical Physics, Saarland University, 66041 Saarbruecken (Germany); Max Planck Institute for the Physics of Complex Systems, Noethnitzer Street 38, 01187 Dresden (Germany)

    2007-11-15

    Mechanical oscillations are important for many cellular processes, e.g. the beating of cilia and flagella or the sensation of sound by hair cells. These dynamic states originate from spontaneous oscillations of molecular motors. A particularly clear example of such oscillations has been observed in muscle fibers under non-physiological conditions. In that case, motor oscillations lead to contraction waves along the fiber. By a macroscopic analysis of muscle fiber dynamics we find that the spontaneous waves involve non-hydrodynamic modes. A simple microscopic model of sarcomere dynamics highlights mechanical aspects of the motor dynamics and fits with the experimental observations.

  16. Human Papillomavirus Infection as a Possible Cause of Spontaneous Abortion and Spontaneous Preterm Delivery

    DEFF Research Database (Denmark)

    Ambühl, Lea Maria Margareta; Baandrup, Ulrik; Dybkær, Karen

    2016-01-01

    , and 10.9% (95% CI; 10.1–11.7) for umbilical cord blood. Summary estimates for HPV prevalence of spontaneous abortions and spontaneous preterm deliveries, in cervix (spontaneous abortions: 24.5%, and pretermdeliveries: 47%, resp.) and placenta (spontaneous abortions: 24.9%, and preterm deliveries: 50......%, resp.), were identified to be higher compared to normal full-term pregnancies (푃 spontaneous abortion, spontaneous preterm...

  17. A Web Resource for Standardized Benchmark Datasets, Metrics, and Rosetta Protocols for Macromolecular Modeling and Design.

    Directory of Open Access Journals (Sweden)

    Shane Ó Conchúir

    Full Text Available The development and validation of computational macromolecular modeling and design methods depend on suitable benchmark datasets and informative metrics for comparing protocols. In addition, if a method is intended to be adopted broadly in diverse biological applications, there needs to be information on appropriate parameters for each protocol, as well as metrics describing the expected accuracy compared to experimental data. In certain disciplines, there exist established benchmarks and public resources where experts in a particular methodology are encouraged to supply their most efficient implementation of each particular benchmark. We aim to provide such a resource for protocols in macromolecular modeling and design. We present a freely accessible web resource (https://kortemmelab.ucsf.edu/benchmarks to guide the development of protocols for protein modeling and design. The site provides benchmark datasets and metrics to compare the performance of a variety of modeling protocols using different computational sampling methods and energy functions, providing a "best practice" set of parameters for each method. Each benchmark has an associated downloadable benchmark capture archive containing the input files, analysis scripts, and tutorials for running the benchmark. The captures may be run with any suitable modeling method; we supply command lines for running the benchmarks using the Rosetta software suite. We have compiled initial benchmarks for the resource spanning three key areas: prediction of energetic effects of mutations, protein design, and protein structure prediction, each with associated state-of-the-art modeling protocols. With the help of the wider macromolecular modeling community, we hope to expand the variety of benchmarks included on the website and continue to evaluate new iterations of current methods as they become available.

  18. Spontaneous emission by moving atoms

    International Nuclear Information System (INIS)

    Meystre, P.; Wilkens, M.

    1994-01-01

    It is well known that spontaneous emission is not an intrinsic atomic property, but rather results from the coupling of the atom to the vacuum modes of the electromagnetic field. As such, it can be modified by tailoring the electromagnetic environment into which the atom can radiate. This was already realized by Purcell, who noted that the spontaneous emission rate can be enhanced if the atom placed inside a cavity is resonant with one of the cavity is resonant with one of the cavity modes, and by Kleppner, who discussed the opposite case of inhibited spontaneous emission. It has also been recognized that spontaneous emission need not be an irreversible process. Indeed, a system consisting of a single atom coupled to a single mode of the electromagnetic field undergoes a periodic exchange of excitation between the atom and the field. This periodic exchange remains dominant as long as the strength of the coupling between the atom and a cavity mode is itself dominant. 23 refs., 6 figs

  19. Spontaneous Development of Moral Concepts

    Science.gov (United States)

    Siegal, M.

    1975-01-01

    Moral competence is more difficult to attain than scientific competence. Since language comprehension plays a central role in conceptual development, and moral language is difficult to learn, there is a common deficiency in moral conceptual development. This suggests a theory of non-spontaneous solutions to moral problems. (Author/MS)

  20. Shell theorem for spontaneous emission

    DEFF Research Database (Denmark)

    Kristensen, Philip Trøst; Mortensen, Jakob Egeberg; Lodahl, Peter

    2013-01-01

    and therefore is given exactly by the dipole approximation theory. This surprising result is a spontaneous emission counterpart to the shell theorems of classical mechanics and electrostatics and provides insights into the physics of mesoscopic emitters as well as great simplifications in practical calculations....

  1. Prediction of Spontaneous Preterm Birth

    NARCIS (Netherlands)

    Dijkstra, Karolien

    2002-01-01

    Preterm birth is a leading cause of neonatal morbidity and mortality. It is a major goal in obstetrics to lower the incidence of spontaneous preterm birth (SPB) and related neonatal morbidity and mortality. One of the principal objectives is to discover early markers that would allow us to identify

  2. EAMJ Dec. Spontaneous.indd

    African Journals Online (AJOL)

    2008-12-12

    Dec 12, 2008 ... surgical abortion at one month gestation without any complication. The second pregnancy which was a year prior resulted in a spontaneous miscarriage at two months followed by evacuation of retained products of conception with no post abortion complications. Antibiotics were taken following both.

  3. Spontaneous fission of superheavy nuclei

    Indian Academy of Sciences (India)

    the Yukawa-plus-exponential potential. The microscopic shell and pairing corrections are obtained using the Strutinsky and BCS approaches and the cranking formulae yield the inertia tensor. Finally, the WKB method is used to calculate penetrabilities and spontaneous fission half-lives. Calculations are performed for the ...

  4. Time-Resolved Macromolecular Crystallography at Modern X-Ray Sources.

    Science.gov (United States)

    Schmidt, Marius

    2017-01-01

    Time-resolved macromolecular crystallography unifies protein structure determination with chemical kinetics. With the advent of fourth generation X-ray sources the time-resolution can be on the order of 10-40 fs, which opens the ultrafast time scale to structure determination. Fundamental motions and transitions associated with chemical reactions in proteins can now be observed. Moreover, new experimental approaches at synchrotrons allow for the straightforward investigation of all kind of reactions in biological macromolecules. Here, recent developments in the field are reviewed.

  5. Macromolecular organization of human centromeric regions reveals high-frequency, polymorphic macro DNA repeats.

    OpenAIRE

    Jabs, E W; Goble, C A; Cutting, G R

    1989-01-01

    To analyze the macromolecular organization of human centromeric regions, we used alpha-satellite, or alphoid, repetitive DNA sequences specific to the centromeres of human chromosomes 6 (D6Z1), X (XC), and Y (YC-2) and the technique of pulsed-field gel electrophoresis. Genomic DNA from 24 normal, unrelated individuals was digested and separated into fragments ranging from 23 kilobases (kb) to 2 megabases (Mb) in length. Digestion with 12 different restriction enzymes with 4- to 8-base-pair re...

  6. Folding and assembly of large macromolecular complexes monitored by hydrogen-deuterium exchange and mass spectrometry

    Directory of Open Access Journals (Sweden)

    Tuma Roman

    2008-04-01

    Full Text Available Abstract Recent advances in protein mass spectrometry (MS have enabled determinations of hydrogen deuterium exchange (HDX in large macromolecular complexes. HDX-MS became a valuable tool to follow protein folding, assembly and aggregation. The methodology has a wide range of applications in biotechnology ranging from quality control for over-expressed proteins and their complexes to screening of potential ligands and inhibitors. This review provides an introduction to protein folding and assembly followed by the principles of HDX and MS detection, and concludes with selected examples of applications that might be of interest to the biotechnology community.

  7. Clustering procedures for the optimal selection of data sets from multiple crystals in macromolecular crystallography

    Science.gov (United States)

    Foadi, James; Aller, Pierre; Alguel, Yilmaz; Cameron, Alex; Axford, Danny; Owen, Robin L.; Armour, Wes; Waterman, David G.; Iwata, So; Evans, Gwyndaf

    2013-01-01

    The availability of intense microbeam macromolecular crystallography beamlines at third-generation synchrotron sources has enabled data collection and structure solution from microcrystals of sets from many crystals of the same protein structure. The associated analysis and merging of multi-crystal data is currently a manual and time-consuming step. Here, a computer program, BLEND, that has been written to assist with and automate many of the steps in this process is described. It is demonstrated how BLEND has successfully been used in the solution of a novel membrane protein. PMID:23897484

  8. Clustering procedures for the optimal selection of data sets from multiple crystals in macromolecular crystallography.

    Science.gov (United States)

    Foadi, James; Aller, Pierre; Alguel, Yilmaz; Cameron, Alex; Axford, Danny; Owen, Robin L; Armour, Wes; Waterman, David G; Iwata, So; Evans, Gwyndaf

    2013-08-01

    The availability of intense microbeam macromolecular crystallography beamlines at third-generation synchrotron sources has enabled data collection and structure solution from microcrystals of data sets from many crystals of the same protein structure. The associated analysis and merging of multi-crystal data is currently a manual and time-consuming step. Here, a computer program, BLEND, that has been written to assist with and automate many of the steps in this process is described. It is demonstrated how BLEND has successfully been used in the solution of a novel membrane protein.

  9. Spontaneous Retropharyngeal Emphysema: A Case Report | Chi ...

    African Journals Online (AJOL)

    ... is a rare clinical condition in pediatric otolaryngology. The predominant symptoms are sore throat, odynophagia, dysphagia, and neck pain. Here, we report a case of spontaneous retropharyngeal emphysema. Keywords: Iatrogenic injury, retropharyngeal emphysema, spontaneous retropharyngeal emphysem, trauma ...

  10. La maladie de Grisel : Spontaneous atlantoaxial subluxation

    NARCIS (Netherlands)

    Meek, MF; Robinson, PH; Hermens, RAEC

    Objective: "La maladie de Grisel" (Grisel's syndrome) is a spontaneously occurring atlantoaxial subluxation with torticollis. We present a case of atlantoaxial subluxation occurring in a 20-year period of pharyngoplasty surgery. The occurrence of a "spontaneous" atlantoaxial subluxation after oral

  11. Assessing physio-macromolecular effects of lactic acid on Zygosaccharomyces bailii cells during microaerobic fermentation.

    Science.gov (United States)

    Kuanyshev, Nurzhan; Ami, Diletta; Signori, Lorenzo; Porro, Danilo; Morrissey, John P; Branduardi, Paola

    2016-08-01

    The ability of Zygosaccharomyces bailii to grow at low pH and in the presence of considerable amounts of weak organic acids, at lethal condition for Saccharomyces cerevisiae, increased the interest in the biotechnological potential of the yeast. To understand the mechanism of tolerance and growth effect of weak acids on Z. bailii, we evaluated the physiological and macromolecular changes of the yeast exposed to sub lethal concentrations of lactic acid. Lactic acid represents one of the important commodity chemical which can be produced by microbial fermentation. We assessed physiological effect of lactic acid by bioreactor fermentation using synthetic media at low pH in the presence of lactic acid. Samples collected from bioreactors were stained with propidium iodide (PI) which revealed that, despite lactic acid negatively influence the growth rate, the number of PI positive cells is similar to that of the control. Moreover, we have performed Fourier Transform Infra-Red (FTIR) microspectroscopy analysis on intact cells of the same samples. This technique has been never applied before to study Z. bailii under this condition. The analyses revealed lactic acid induced macromolecular changes in the overall cellular protein secondary structures, and alterations of cell wall and membrane physico-chemical properties. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  12. Time-efficient, high-resolution, whole brain three-dimensional macromolecular proton fraction mapping.

    Science.gov (United States)

    Yarnykh, Vasily L

    2016-05-01

    Macromolecular proton fraction (MPF) mapping is a quantitative MRI method that reconstructs parametric maps of a relative amount of macromolecular protons causing the magnetization transfer (MT) effect and provides a biomarker of myelination in neural tissues. This study aimed to develop a high-resolution whole brain MPF mapping technique using a minimal number of source images for scan time reduction. The described technique was based on replacement of an actually acquired reference image without MT saturation by a synthetic one reconstructed from R1 and proton density maps, thus requiring only three source images. This approach enabled whole brain three-dimensional MPF mapping with isotropic 1.25 × 1.25 × 1.25 mm(3) voxel size and a scan time of 20 min. The synthetic reference method was validated against standard MPF mapping with acquired reference images based on data from eight healthy subjects. Mean MPF values in segmented white and gray matter appeared in close agreement with no significant bias and small within-subject coefficients of variation (maps demonstrated sharp white-gray matter contrast and clear visualization of anatomical details, including gray matter structures with high iron content. The proposed synthetic reference method improves resolution of MPF mapping and combines accurate MPF measurements with unique neuroanatomical contrast features. © 2015 Wiley Periodicals, Inc.

  13. Long-wavelength macromolecular crystallography - First successful native SAD experiment close to the sulfur edge

    Science.gov (United States)

    Aurelius, O.; Duman, R.; El Omari, K.; Mykhaylyk, V.; Wagner, A.

    2017-11-01

    Phasing of novel macromolecular crystal structures has been challenging since the start of structural biology. Making use of anomalous diffraction of natively present elements, such as sulfur and phosphorus, for phasing has been possible for some systems, but hindered by the necessity to access longer X-ray wavelengths in order to make most use of the anomalous scattering contributions of these elements. Presented here are the results from a first successful experimental phasing study of a macromolecular crystal structure at a wavelength close to the sulfur K edge. This has been made possible by the in-vacuum setup and the long-wavelength optimised experimental setup at the I23 beamline at Diamond Light Source. In these early commissioning experiments only standard data collection and processing procedures have been applied, in particular no dedicated absorption correction has been used. Nevertheless the success of the experiment demonstrates that the capability to extract phase information can be even further improved once data collection protocols and data processing have been optimised.

  14. A brief history of macromolecular crystallography, illustrated by a family tree and its Nobel fruits.

    Science.gov (United States)

    Jaskolski, Mariusz; Dauter, Zbigniew; Wlodawer, Alexander

    2014-09-01

    As a contribution to the celebration of the year 2014, declared by the United Nations to be 'The International Year of Crystallography', the FEBS Journal is dedicating this issue to papers showcasing the intimate union between macromolecular crystallography and structural biology, both in historical perspective and in current research. Instead of a formal editorial piece, by way of introduction, this review discusses the most important, often iconic, achievements of crystallographers that led to major advances in our understanding of the structure and function of biological macromolecules. We identified at least 42 scientists who received Nobel Prizes in Physics, Chemistry or Medicine for their contributions that included the use of X-rays or neutrons and crystallography, including 24 who made seminal discoveries in macromolecular sciences. Our spotlight is mostly, but not only, on the recipients of this most prestigious scientific honor, presented in approximately chronological order. As a summary of the review, we attempt to construct a genealogy tree of the principal lineages of protein crystallography, leading from the founding members to the present generation. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.

  15. Macromolecular metabolism of a differentiated rat keratinocyte culture system following exposure to sulfur mustard

    International Nuclear Information System (INIS)

    Vaughan, F.L.; Zaman, S.; Scavarelli, R.; Bernstein, I.A.

    1988-01-01

    A method for producing a stratified, squamous epithelium in vitro by cultivating rat keratinocytes on nylon membranes has been developed in this laboratory. This epidermal-like culture is being used to obtain a better understanding of the mechanism of skin vesication after topical exposure to the sulfur mustard bis(beta-chloroethyl) sulfide (BCES) dissolved in a selected solvent. Radiolabeled macromolecular precursors (thymidine, uridine, and leucine) have been used to study the effect of BCES on the synthesis of DNA, RNA, and protein, respectively, after topical exposure to the mustard at concentrations of 0.01-500 nmol/cm2 dissolved in 70% dimethyl sulfoxide (DMSO). From these and other studies it has been determined that exposure to even the low concentration of 0.01 nmol BCES/cm2 for 30 min results in significant inhibition of [ 3 H]thymidine incorporation, although complete recovery occurs by 24 h. Significant inhibition of [ 3 H]uridine and [ 14 C]leucine incorporation is observed only after exposure to much higher concentrations of BCES (10-500 nmol/cm2). This suggests a very early lesion in macromolecular metabolism with DNA being the primary target

  16. Macromolecular Crowding Studies of Amino Acids Using NMR Diffusion Measurements and Molecular Dynamics Simulations

    Directory of Open Access Journals (Sweden)

    Amninder S Virk

    2015-02-01

    Full Text Available Molecular crowding occurs when the total concentration of macromolecular species in a solution is so high that a considerable proportion of the volume is physically occupied and therefore not accessible to other molecules. This results in significant changes in the solution properties of the molecules in such systems. Macromolecular crowding is ubiquitous in biological systems due to the generally high intracellular protein concentrations. The major hindrance to understanding crowding is the lack of direct comparison of experimental data with theoretical or simulated data. Self-diffusion is sensitive to changes in the molecular weight and shape of the diffusing species, and the available diffusion space (i.e., diffusive obstruction. Consequently, diffusion measurements are a direct means for probing crowded systems including the self-association of molecules. In this work, nuclear magnetic resonance measurements of the self-diffusion of four amino acids (glycine, alanine, valine and phenylalanine up to their solubility limit in water were compared directly with molecular dynamics simulations. The experimental data were then analyzed using various models of aggregation and obstruction. Both experimental and simulated data revealed that the diffusion of both water and the amino acids were sensitive to the amino acid concentration. The direct comparison of the simulated and experimental data afforded greater insights into the aggregation and obstruction properties of each amino acid.

  17. The development of delivery agents that facilitate the oral absorption of macromolecular drugs.

    Science.gov (United States)

    Leone-Bay, A; Paton, D R; Weidner, J J

    2000-03-01

    Macromolecules comprise a growing group of new drugs with great clinical promise. To date, the therapeutic application of these drugs has been limited, because they are effective only when administered parenterally. Unfortunately, macromolecular drugs are not absorbed following nonparenteral dosing, because the mechanisms of the human body are designed to degrade and/or exclude them. To overcome the numerous obstacles to the noninvasive delivery of these drugs, various approaches are under investigation including the use of delivery agents to promote drug absorption. This review provides a summary of the novel approaches currently in progress in the areas of transdermal, transmucosal, and oral delivery of macromolecular drugs facilitated by delivery agents. We review our own novel work in this area in some detail, including the methods developed for the synthesis of the delivery agents, in vitro screening techniques developed to select compounds for in vivo testing, and the results of in vivo screening in both rats and primates, including preliminary safety and efficacy studies. Finally, the results of Phase I clinical studies showing the oral delivery of heparin are presented. Copyright 2000 John Wiley & Sons, Inc.

  18. Resolving macromolecular structures from electron cryo-tomography data using subtomogram averaging in RELION.

    Science.gov (United States)

    Bharat, Tanmay A M; Scheres, Sjors H W

    2016-11-01

    Electron cryo-tomography (cryo-ET) is a technique that is used to produce 3D pictures (tomograms) of complex objects such as asymmetric viruses, cellular organelles or whole cells from a series of tilted electron cryo-microscopy (cryo-EM) images. Averaging of macromolecular complexes found within tomograms is known as subtomogram averaging, and this technique allows structure determination of macromolecular complexes in situ. Subtomogram averaging is also gaining in popularity for the calculation of initial models for single-particle analysis. We describe herein a protocol for subtomogram averaging from cryo-ET data using the RELION software (http://www2.mrc-lmb.cam.ac.uk/relion). RELION was originally developed for cryo-EM single-particle analysis, and the subtomogram averaging approach presented in this protocol has been implemented in the existing workflow for single-particle analysis so that users may conveniently tap into existing capabilities of the RELION software. We describe how to calculate 3D models for the contrast transfer function (CTF) that describe the transfer of information in the imaging process, and we illustrate the results of classification and subtomogram averaging refinement for cryo-ET data of purified hepatitis B capsid particles and Saccharomyces cerevisiae 80S ribosomes. Using the steps described in this protocol, along with the troubleshooting and optimization guidelines, high-resolution maps can be obtained in which secondary structure elements are resolved subtomogram.

  19. ISPyB: an information management system for synchrotron macromolecular crystallography.

    Science.gov (United States)

    Delagenière, Solange; Brenchereau, Patrice; Launer, Ludovic; Ashton, Alun W; Leal, Ricardo; Veyrier, Stéphanie; Gabadinho, José; Gordon, Elspeth J; Jones, Samuel D; Levik, Karl Erik; McSweeney, Seán M; Monaco, Stéphanie; Nanao, Max; Spruce, Darren; Svensson, Olof; Walsh, Martin A; Leonard, Gordon A

    2011-11-15

    Individual research groups now analyze thousands of samples per year at synchrotron macromolecular crystallography (MX) resources. The efficient management of experimental data is thus essential if the best possible experiments are to be performed and the best possible data used in downstream processes in structure determination pipelines. Information System for Protein crystallography Beamlines (ISPyB), a Laboratory Information Management System (LIMS) with an underlying data model allowing for the integration of analyses down-stream of the data collection experiment was developed to facilitate such data management. ISPyB is now a multisite, generic LIMS for synchrotron-based MX experiments. Its initial functionality has been enhanced to include improved sample tracking and reporting of experimental protocols, the direct ranking of the diffraction characteristics of individual samples and the archiving of raw data and results from ancillary experiments and post-experiment data processing protocols. This latter feature paves the way for ISPyB to play a central role in future macromolecular structure solution pipelines and validates the application of the approach used in ISPyB to other experimental techniques, such as biological solution Small Angle X-ray Scattering and spectroscopy, which have similar sample tracking and data handling requirements.

  20. Systematics of spontaneous positron lines

    International Nuclear Information System (INIS)

    Mueller, U.; Reus, T. de; Reinhardt, J.; Mueller, B.; Greiner, W.

    1985-08-01

    Dynamical and spontaneous positron emission are investigated for heavy-ion collisions with long time delay using a semiclassical description. Numerical results and analytical expressions for the characteristic quantities of the resulting spontaneous positron line, i.e., its position, width, and cross section, are compared. The expected behaviour of the line position and cross section and its visibility against the spectrum of dynamically created positrons is discussed in dependence of the united charge Zsub(u) of projectile and target nucleus in a range of systems from Zsub(u)=180 up to Zsub(u)=188. The results are confronted with presently available experimental data, and possible implications on further experiments are worked out. (orig.)

  1. Spontaneous Rotational Inversion in Phycomyces

    KAUST Repository

    Goriely, Alain

    2011-03-01

    The filamentary fungus Phycomyces blakesleeanus undergoes a series of remarkable transitions during aerial growth. During what is known as the stagea IV growth phase, the fungus extends while rotating in a counterclockwise manner when viewed from above (stagea IVa) and then, while continuing to grow, spontaneously reverses to a clockwise rotation (stagea IVb). This phase lasts for 24-48Ah and is sometimes followed by yet another reversal (stageAIVc) before the overall growth ends. Here, we propose a continuum mechanical model of this entire process using nonlinear, anisotropic, elasticity and show how helical anisotropy associated with the cell wall structure can induce spontaneous rotation and, under appropriate circumstances, the observed reversal of rotational handedness. © 2011 American Physical Society.

  2. Spontaneous regression of colon cancer.

    Science.gov (United States)

    Kihara, Kyoichi; Fujita, Shin; Ohshiro, Taihei; Yamamoto, Seiichiro; Sekine, Shigeki

    2015-01-01

    A case of spontaneous regression of transverse colon cancer is reported. A 64-year-old man was diagnosed as having cancer of the transverse colon at a local hospital. Initial and second colonoscopy examinations revealed a typical cancer of the transverse colon, which was diagnosed as moderately differentiated adenocarcinoma. The patient underwent right hemicolectomy 6 weeks after the initial colonoscopy. The resected specimen showed only a scar at the tumor site, and no cancerous tissue was proven histologically. The patient is alive with no evidence of recurrence 1 year after surgery. Although an antitumor immune response is the most likely explanation, the exact nature of the phenomenon was unclear. We describe this rare case and review the literature pertaining to spontaneous regression of colorectal cancer. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  3. Management of intractable spontaneous epistaxis

    Science.gov (United States)

    Rudmik, Luke

    2012-01-01

    Background: Epistaxis is a common otolaryngology emergency and is often controlled with first-line interventions such as cautery, hemostatic agents, or anterior nasal packing. A subset of patients will continue to bleed and require more aggressive therapy. Methods: Intractable spontaneous epistaxis was traditionally managed with posterior nasal packing and prolonged hospital admission. In an effort to reduce patient morbidity and shorten hospital stay, surgical and endovascular techniques have gained popularity. A literature review was conducted. Results: Transnasal endoscopic sphenopalatine artery ligation and arterial embolization provide excellent control rates but the decision to choose one over the other can be challenging. The role of transnasal endoscopic anterior ethmoid artery ligation is unclear but may be considered in certain cases when bleeding localizes to the ethmoid region. Conclusion: This article will focus on the management of intractable spontaneous epistaxis and discuss the role of endoscopic arterial ligation and embolization as it pertains to this challenging clinical scenario. PMID:22391084

  4. MX1: a bending-magnet crystallography beamline serving both chemical and macromolecular crystallography communities at the Australian Synchrotron

    International Nuclear Information System (INIS)

    Cowieson, Nathan Philip; Aragao, David; Clift, Mark; Ericsson, Daniel J.; Gee, Christine; Harrop, Stephen J.; Mudie, Nathan; Panjikar, Santosh; Price, Jason R.; Riboldi-Tunnicliffe, Alan; Williamson, Rachel; Caradoc-Davies, Tom

    2015-01-01

    The macromolecular crystallography beamline MX1 at the Australian Synchrotron is described. MX1 is a bending-magnet crystallography beamline at the 3 GeV Australian Synchrotron. The beamline delivers hard X-rays in the energy range from 8 to 18 keV to a focal spot at the sample position of 120 µm FWHM. The beamline endstation and ancillary equipment facilitate local and remote access for both chemical and biological macromolecular crystallography. Here, the design of the beamline and endstation are discussed. The beamline has enjoyed a full user program for the last seven years and scientific highlights from the user program are also presented

  5. Spontaneous baryogenesis in warm inflation

    OpenAIRE

    Brandenberger, Robert H.; Yamaguchi, Masahide

    2003-01-01

    We discuss spontaneous baryogenesis in the warm inflation scenario. In contrast with standard inflation models, radiation always exists in the warm inflation scenario, and the inflaton must be directly coupled to it. Also, the transition to the post-inflationary radiation dominated phase is smooth and the entropy is not significantly increased at the end of the period of inflation. In addition, after the period of warm inflation ends, the inflaton does not oscillate coherently but slowly roll...

  6. Possible genetic damage from diagnostic x irradiation. A review

    International Nuclear Information System (INIS)

    Withrow, T.J.; Andersen, F.A.; Yao, K.T.S.; Stratmeyer, M.E.

    1980-08-01

    Although it is known that x irradiation is capable of producing mutations and chromosomal abnormalities in experimental systems, there is little or no direct evidence of such phenomena in humans. This report reviews some human genetic diseases and chromosomal abnormalities as well as the evidence for x-ray induced mutations and chromosomal abnormalities in experimental systems. The examination of these areas reveals that spontaneous chromosomal abnormalities and genetic diseases are associated with the same type of DNA damage that x irradiation produces in experimental systems. Therefore, it is concluded that genetic radiation damage in humans may mainfest itself as an increase in the spontaneous genetic diseases rather than as any unique disease

  7. Spontaneous Splenic Rupture in Melanoma

    Directory of Open Access Journals (Sweden)

    Hadi Mirfazaelian

    2014-01-01

    Full Text Available Spontaneous rupture of spleen due to malignant melanoma is a rare situation, with only a few case reports in the literature. This study reports a previously healthy, 30-year-old man who came with chief complaint of acute abdominal pain to emergency room. On physical examination, abdominal tenderness and guarding were detected to be coincident with hypotension. Ultrasonography revealed mild splenomegaly with moderate free fluid in abdominopelvic cavity. Considering acute abdominal pain and hemodynamic instability, he underwent splenectomy with splenic rupture as the source of bleeding. Histologic examination showed diffuse infiltration by tumor. Immunohistochemical study (positive for S100, HMB45, and vimentin and negative for CK, CD10, CK20, CK7, CD30, LCA, EMA, and chromogranin confirmed metastatic malignant melanoma. On further questioning, there was a past history of a nasal dark skin lesion which was removed two years ago with no pathologic examination. Spontaneous (nontraumatic rupture of spleen is an uncommon situation and it happens very rarely due to neoplastic metastasis. Metastasis of malignant melanoma is one of the rare causes of the spontaneous rupture of spleen.

  8. Structural damage

    International Nuclear Information System (INIS)

    Gray, R.E.; Bruhn, R.W.

    1992-01-01

    Virtually all structures show some signs of distress due to deterioration of the building components, to changed loads, or to changed support conditions. Changed support conditions result from ground movements. In mining regions many cases of structural distress are attributed to mining without considering alternative causes. This is particularly true of coal mining since it occurs under extensive areas. Coal mining is estimated to have already undermined more than eight million acres and may eventually undermine 40 million acres in the United States. Other nonmetal and metal underground mines impact much smaller areas. Although it is sometimes difficult, even with careful study, to identify the actual cause of damage, persons responsible for underground coal mining should at least be aware of possible causes of building stress other than mine subsidence. This paper presents information on distress to structures and briefly reviews a number of causes of ground movements other than subsidence: Mass movements, dissolution, erosion, frost action, shrinking and swelling, yield into excavations and compressibility

  9. Damaged Skylab

    Science.gov (United States)

    1973-01-01

    The Saturn V vehicle, carrying the unmarned orbital workshop for the Skylab-1 mission, lifted off successfully and all systems performed normally. Sixty-three seconds into the flight, engineers in the operation support and control center saw an unexpected telemetry indication that signalled that damages occurred on one solar array and the micrometeoroid shield during the launch. The micrometeoroid shield, a thin protective cylinder surrounding the workshop protecting it from tiny space particles and the sun's scorching heat, ripped loose from its position around the workshop. This caused the loss of one solar wing and jammed the other. Still unoccupied, the Skylab was stricken with the loss of the heat shield and sunlight beat mercilessly on the lab's sensitive skin. Internal temperatures soared, rendering the station uninhabitable, threatening foods, medicines, films, and experiments. This image, taken during a fly-around inspection by the Skylab-2 crew, shows a crippled Skylab in orbit. The crew found their home in space to be in serious shape; the heat shield gone, one solar wing gone, and the other jammed. The Marshall Space Flight Center (MSFC) developed, tested, rehearsed, and approved three repair options. These options included a parasol sunshade and a twin-pole sunshade to restore the temperature inside the workshop, and a set of metal cutting tools to free the jammed solar panel.

  10. RosettaScripts: a scripting language interface to the Rosetta macromolecular modeling suite.

    Science.gov (United States)

    Fleishman, Sarel J; Leaver-Fay, Andrew; Corn, Jacob E; Strauch, Eva-Maria; Khare, Sagar D; Koga, Nobuyasu; Ashworth, Justin; Murphy, Paul; Richter, Florian; Lemmon, Gordon; Meiler, Jens; Baker, David

    2011-01-01

    Macromolecular modeling and design are increasingly useful in basic research, biotechnology, and teaching. However, the absence of a user-friendly modeling framework that provides access to a wide range of modeling capabilities is hampering the wider adoption of computational methods by non-experts. RosettaScripts is an XML-like language for specifying modeling tasks in the Rosetta framework. RosettaScripts provides access to protocol-level functionalities, such as rigid-body docking and sequence redesign, and allows fast testing and deployment of complex protocols without need for modifying or recompiling the underlying C++ code. We illustrate these capabilities with RosettaScripts protocols for the stabilization of proteins, the generation of computationally constrained libraries for experimental selection of higher-affinity binding proteins, loop remodeling, small-molecule ligand docking, design of ligand-binding proteins, and specificity redesign in DNA-binding proteins.

  11. Phenix - a comprehensive python-based system for macromolecular structure solution

    Energy Technology Data Exchange (ETDEWEB)

    Terwilliger, Thomas C [Los Alamos National Laboratory; Hung, Li - Wei [Los Alamos National Laboratory; Adams, Paul D [UC BERKELEY; Afonine, Pavel V [UC BERKELEY; Bunkoczi, Gabor [UNIV OF CAMBRIDGE; Chen, Vincent B [DUKE UNIV; Davis, Ian [DUKE UNIV; Echols, Nathaniel [LBNL; Headd, Jeffrey J [DUKE UNIV; Grosse Kunstleve, Ralf W [LBNL; Mccoy, Airlie J [UNIV OF CAMBRIDGE; Moriarty, Nigel W [LBNL; Oeffner, Robert [UNIV OF CAMBRIDGE; Read, Randy J [UNIV OF CAMBRIDGE; Richardson, David C [DUKE UNIV; Richardson, Jane S [DUKE UNIV; Zwarta, Peter H [LBNL

    2009-01-01

    Macromolecular X-ray crystallography is routinely applied to understand biological processes at a molecular level. However, significant time and effort are still required to solve and complete many of these structures because of the need for manual interpretation of complex numerical data using many software packages, and the repeated use of interactive three-dimensional graphics. Phenix has been developed to provide a comprehensive system for crystallographic structure solution with an emphasis on automation of all procedures. This has relied on the development of algorithms that minimize or eliminate subjective input, the development of algorithms that automate procedures that are traditionally performed by hand, and finally the development of a framework that allows a tight integration between the algorithms.

  12. Mix and Inject: Reaction Initiation by Diffusion for Time-Resolved Macromolecular Crystallography

    Directory of Open Access Journals (Sweden)

    Marius Schmidt

    2013-01-01

    Full Text Available Time-resolved macromolecular crystallography unifies structure determination with chemical kinetics, since the structures of transient states and chemical and kinetic mechanisms can be determined simultaneously from the same data. To start a reaction in an enzyme, typically, an initially inactive substrate present in the crystal is activated. This has particular disadvantages that are circumvented when active substrate is directly provided by diffusion. However, then it is prohibitive to use macroscopic crystals because diffusion times become too long. With small micro- and nanocrystals diffusion times are adequately short for most enzymes and the reaction can be swiftly initiated. We demonstrate here that a time-resolved crystallographic experiment becomes feasible by mixing substrate with enzyme nanocrystals which are subsequently injected into the X-ray beam of a pulsed X-ray source.

  13. Ground Based Program for the Physical Analysis of Macromolecular Crystal Growth

    Science.gov (United States)

    Malkin, Alexander J.

    1999-01-01

    In a reported period in situ atomic force microscopy was utilized in our laboratory to study mechanisms of growth and kinetics of crystallization of ten protein and virus crystals. These included canavalin, thaumatin, apoferritin, lipase, catalase, t-RNA, lysozyme, xylanase, turnip yellow mosaic virus (TYMV) and satellite tobacco mosaic virus (STMV). We have also designed and constructed in our laboratory both in situ conventional two-beam Michelson and phase shift Mach-Zenhder interferometers. Computer software for the processing of the interferometric images was developed as well. Interferometric techniques were applied for studies of growth kinetics and transport phenomena in crystallization of several macromolecular crystals. As a result of this work we have published 21 papers and have given many presentations at international and national meetings. A list of these publications and conference presentations is attached.

  14. OCTOPUS: an innovative multimodal diffractometer for neutron macromolecular crystallography across the length scales

    International Nuclear Information System (INIS)

    Blakeley, M.P.; Andersen, K.; Kreuz, M.; Giroud, B.; McSweeney, S.; Mitchell, E.; Teixeira, S.C.M.; Forsyth, V.T.

    2011-01-01

    We propose to construct a novel protein diffractometer at position H112B. The new instrument will deliver major efficiency gains, as well as offering greatly extended flexibility through the option of several easily interchangeable modes of operation. This proposal builds on the demonstrable need to extend ILL's capacity for high resolution structural studies of protein systems, as well as a need to widen the scope of biological crystallography - in particular for monochromatic studies at both high and low resolution. The development will be carried out in close collaboration with structural biologists at the ESRF, and engineered in such a way that the user interface of the instrument (from sample to software) will be transparently identifiable to a large, dynamic, and driven community of European synchrotron X-ray macromolecular crystallographers. (authors)

  15. A vibrating membrane bioreactor (VMBR): Macromolecular transmission-influence of extracellular polymeric substances

    DEFF Research Database (Denmark)

    Beier, Søren; Jonsson, Gunnar Eigil

    2009-01-01

    The vibrating membrane bioreactor (VMBR) system facilitates the possibility of conducting a separation of macromolecules (BSA) from larger biological components (yeast cells) with a relatively high and stable macromolecular transmission at sub-critical flux. This is not possible to achieve...... for a static non-vibrating membrane module. A BSA transmission of 74% has been measured in the separation of 4g/L BSA from 8 g/L dry weight yeast cells in suspension at sub-critical flux (20L/(m(2) h)). However, this transmission is lower than the 85% BSA transmission measured for at pure 4g/L BSA solution...... of around 32% is measured for a pure yeast cell suspension. Thus, EPS and BSA are "competing" in being transmitted which might explain the lowered BSA transmission in the presence of yeast cells. Additionally, EPS heavily foul the membranes, leading to a 86% permeability drop and a fouling resistance 6...

  16. Functionalization of Planet-Satellite Nanostructures Revealed by Nanoscopic Localization of Distinct Macromolecular Species.

    Science.gov (United States)

    Rossner, Christian; Roddatis, Vladimir; Lopatin, Sergei; Vana, Philipp

    2016-11-01

    The development of a straightforward method is reported to form hybrid polymer/gold planet-satellite nanostructures (PlSNs) with functional polymer. Polyacrylate type polymer with benzyl chloride in its backbone as a macromolecular tracer is synthesized to study its localization within PlSNs by analyzing the elemental distribution of chlorine. The functionalized nanohybrid structures are analyzed by scanning transmission electron microscopy, electron energy loss spectroscopy, and spectrum imaging. The results show that the RAFT (reversible addition-fragmentation chain transfer) polymers' sulfur containing end groups are colocalized at the gold cores, both within nanohybrids of simple core-shell morphology and within higher order PlSNs, providing microscopic evidence for the affinity of the RAFT group toward gold surfaces. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. A Test of Macromolecular Crystallization in Microgravity: Large, Well-Ordered Insulin Crystals

    Science.gov (United States)

    Borgstahl, Gloria E. O.; Vahedi-Faridi, Ardeschir; Lovelace, Jeff; Bellamy, Henry D.; Snell, Edward H.; Whitaker, Ann F. (Technical Monitor)

    2001-01-01

    Crystals of insulin grown in microgravity on space shuttle mission STS-95 were extremely well-ordered and unusually large (many > 2 mm). The physical characteristics of six microgravity and six earth-grown crystals were examined by X-ray analysis employing superfine f slicing and unfocused synchrotron radiation. This experimental setup allowed hundreds of reflections to be precisely examined for each crystal in a short period of time. The microgravity crystals were on average 34 times larger, had 7 times lower mosaicity, had 54 times higher reflection peak heights and diffracted to significantly higher resolution than their earth grown counterparts. A single mosaic domain model could account for reflections in microgravity crystals whereas reflections from earth crystals required a model with multiple mosaic domains. This statistically significant and unbiased characterization indicates that the microgravity environment was useful for the improvement of crystal growth and resultant diffraction quality in insulin crystals and may be similarly useful for macromolecular crystals in general.

  18. Functionalization of Planet-Satellite Nanostructures Revealed by Nanoscopic Localization of Distinct Macromolecular Species

    KAUST Repository

    Rossner, Christian

    2016-09-26

    The development of a straightforward method is reported to form hybrid polymer/gold planet-satellite nanostructures (PlSNs) with functional polymer. Polyacrylate type polymer with benzyl chloride in its backbone as a macromolecular tracer is synthesized to study its localization within PlSNs by analyzing the elemental distribution of chlorine. The functionalized nanohybrid structures are analyzed by scanning transmission electron microscopy, electron energy loss spectroscopy, and spectrum imaging. The results show that the RAFT (reversible addition-fragmentation chain transfer) polymers\\' sulfur containing end groups are colocalized at the gold cores, both within nanohybrids of simple core-shell morphology and within higher order PlSNs, providing microscopic evidence for the affinity of the RAFT group toward gold surfaces. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA., Weinheim.

  19. C1 Polymerization: a unique tool towards polyethylene-based complex macromolecular architectures

    KAUST Repository

    Wang, De

    2017-05-09

    The recent developments in organoborane initiated C1 polymerization (chain grows by one atom at a time) of ylides opens unique horizons towards well-defined/perfectly linear polymethylenes (equivalent to polyethylenes, PE) and PE-based complex macromolecular architectures. The general mechanism of C1 polymerization (polyhomologation) involves the formation of a Lewis complex between a methylide (monomer) and a borane (initiator), followed by migration/insertion of a methylene into the initiator and after oxidation/hydrolysis to afford OH-terminated polyethylenes. This review summarizes efforts towards conventional and newly discovered borane-initiators and ylides (monomers), as well as a combination of polyhomologation with other polymerization methods. Initial efforts dealing with C3 polymerization and the synthesis of the first C1/C3 copolymers are also given. Finally, some thoughts for the future of these polymerizations are presented.

  20. Site-selective electroless nickel plating on patterned thin films of macromolecular metal complexes.

    Science.gov (United States)

    Kimura, Mutsumi; Yamagiwa, Hiroki; Asakawa, Daisuke; Noguchi, Makoto; Kurashina, Tadashi; Fukawa, Tadashi; Shirai, Hirofusa

    2010-12-01

    We demonstrate a simple route to depositing nickel layer patterns using photocross-linked polymer thin films containing palladium catalysts, which can be used as adhesive interlayers for fabrication of nickel patterns on glass and plastic substrates. Electroless nickel patterns can be obtained in three steps: (i) the pattern formation of partially quaterized poly(vinyl pyridine) by UV irradiation, (ii) the formation of macromolecular metal complex with palladium, and (iii) the nickel metallization using electroless plating bath. Metallization is site-selective and allows for a high resolution. And the resulting nickel layered structure shows good adhesion with glass and plastic substrates. The direct patterning of metallic layers onto insulating substrates indicates a great potential for fabricating micro/nano devices.

  1. Integration and global analysis of isothermal titration calorimetry data for studying macromolecular interactions.

    Science.gov (United States)

    Brautigam, Chad A; Zhao, Huaying; Vargas, Carolyn; Keller, Sandro; Schuck, Peter

    2016-05-01

    Isothermal titration calorimetry (ITC) is a powerful and widely used method to measure the energetics of macromolecular interactions by recording a thermogram of differential heating power during a titration. However, traditional ITC analysis is limited by stochastic thermogram noise and by the limited information content of a single titration experiment. Here we present a protocol for bias-free thermogram integration based on automated shape analysis of the injection peaks, followed by combination of isotherms from different calorimetric titration experiments into a global analysis, statistical analysis of binding parameters and graphical presentation of the results. This is performed using the integrated public-domain software packages NITPIC, SEDPHAT and GUSSI. The recently developed low-noise thermogram integration approach and global analysis allow for more precise parameter estimates and more reliable quantification of multisite and multicomponent cooperative and competitive interactions. Titration experiments typically take 1-2.5 h each, and global analysis usually takes 10-20 min.

  2. A novel approach for assesing macromolecular complexes combining soft-docking calculations with NMR data

    Science.gov (United States)

    Morelli, Xavier J.; Palma, P. Nuno; Guerlesquin, Françoise; Rigby, Alan C.

    2001-01-01

    We present a novel and efficient approach for assessing protein–protein complex formation, which combines ab initio docking calculations performed with the protein docking algorithm BiGGER and chemical shift perturbation data collected with heteronuclear single quantum coherence (HSQC) or TROSY nuclear magnetic resonance (NMR) spectroscopy. This method, termed "restrained soft-docking," is validated for several known protein complexes. These data demonstrate that restrained soft-docking extends the size limitations of NMR spectroscopy and provides an alternative method for investigating macromolecular protein complexes that requires less experimental time, effort, and resources. The potential utility of this novel NMR and simulated docking approach in current structural genomic initiatives is discussed. PMID:11567104

  3. Reliable and efficient solution of genome-scale models of Metabolism and macromolecular Expression

    DEFF Research Database (Denmark)

    Ma, Ding; Yang, Laurence; Fleming, Ronan M. T.

    2017-01-01

    Constraint-Based Reconstruction and Analysis (COBRA) is currently the only methodology that permits integrated modeling of Metabolism and macromolecular Expression (ME) at genome-scale. Linear optimization computes steady-state flux solutions to ME models, but flux values are spread over many ord...... problems tested here. DQQ will enable extensive use of large linear and nonlinear models in systems biology and other applications involving multiscale data....... orders of magnitude. Data values also have greatly varying magnitudes. Standard double-precision solvers may return inaccurate solutions or report that no solution exists. Exact simplex solvers based on rational arithmetic require a near-optimal warm start to be practical on large problems (current ME...

  4. Automated Protocols for Macromolecular Crystallization at the MRC Laboratory of Molecular Biology.

    Science.gov (United States)

    Gorrec, Fabrice; Löwe, Jan

    2018-01-24

    When high quality crystals are obtained that diffract X-rays, the crystal structure may be solved at near atomic resolution. The conditions to crystallize proteins, DNAs, RNAs, and their complexes can however not be predicted. Employing a broad variety of conditions is a way to increase the yield of quality diffraction crystals. Two fully automated systems have been developed at the MRC Laboratory of Molecular Biology (Cambridge, England, MRC-LMB) that facilitate crystallization screening against 1,920 initial conditions by vapor diffusion in nanoliter droplets. Semi-automated protocols have also been developed to optimize conditions by changing the concentrations of reagents, the pH, or by introducing additives that potentially enhance properties of the resulting crystals. All the corresponding protocols will be described in detail and briefly discussed. Taken together, they enable convenient and highly efficient macromolecular crystallization in a multi-user facility, while giving the users control over key parameters of their experiments.

  5. Proceedings of a one-week course on exploiting anomalous scattering in macromolecular structure determination (EMBO'07)

    Energy Technology Data Exchange (ETDEWEB)

    Weiss, M.S.; Shepard, W.; Dauter, Z.; Leslie, A.; Diederichs, K.; Evans, G.; Svensson, O.; Schneider, T.; Bricogne, G.; Dauter, Z.; Flensburg, C.; Terwilliger, T.; Lamzin, V.; Leslie, A.; Kabsch, W.; Flensburg, C.; Terwilliger, T.; Lamzin, V.; Read, R.; Panjikar, S.; Pannu, N.S.; Dauter, Z.; Weiss, M.S.; McSweeney, S

    2007-07-01

    This course, which was directed to young scientists, illustrated both theoretical and practical aspects of macromolecular crystal structure solution using synchrotron radiation. Some software dedicated to data collection, processing and analysis were presented. This document gathers only the slides of the presentations.

  6. Macromolecular crowding compacts unfolded apoflavodoxin and causes severe aggregation of the off-pathway intermediate during apoflavodoxin folding

    NARCIS (Netherlands)

    Engel, R.; Westphal, A.H.; Huberts, D.; Nabuurs, S.M.; Lindhoud, S.; Visser, A.J.W.G.; Mierlo, van C.P.M.

    2008-01-01

    To understand how proteins fold in vivo, it is important to investigate the effects of macromolecular crowding on protein folding. Here, the influence of crowding on in vitro apoflavodoxin folding, which involves a relatively stable off-pathway intermediate with molten globule characteristics, is

  7. Errors in macromolecular synthesis after stress : a study of the possible protective role of the small heat shock proteins

    NARCIS (Netherlands)

    Marin Vinader, L.

    2006-01-01

    The general goal of this thesis was to gain insight in what small heat shock proteins (sHsps) do with respect to macromolecular synthesis during a stressful situation in the cell. It is known that after a non-lethal heat shock, cells are better protected against a subsequent more severe heat shock,

  8. Proceedings of a one-week course on exploiting anomalous scattering in macromolecular structure determination (EMBO'07)

    International Nuclear Information System (INIS)

    Weiss, M.S.; Shepard, W.; Dauter, Z.; Leslie, A.; Diederichs, K.; Evans, G.; Svensson, O.; Schneider, T.; Bricogne, G.; Dauter, Z.; Flensburg, C.; Terwilliger, T.; Lamzin, V.; Leslie, A.; Kabsch, W.; Flensburg, C.; Terwilliger, T.; Lamzin, V.; Read, R.; Panjikar, S.; Pannu, N.S.; Dauter, Z.; Weiss, M.S.; McSweeney, S.

    2007-01-01

    This course, which was directed to young scientists, illustrated both theoretical and practical aspects of macromolecular crystal structure solution using synchrotron radiation. Some software dedicated to data collection, processing and analysis were presented. This document gathers only the slides of the presentations

  9. Macromolecular bipill of gemcitabine and methotrexate facilitates tumor-specific dual drug therapy with higher benefit-to-risk ratio

    DEFF Research Database (Denmark)

    Das, Manasmita; Jain, Roopal; Agrawal, Ashish Kumar

    2014-01-01

    The present study reports the synthesis, characterization, and biological evaluation of a novel macromolecular bipill, synthesized by appending two different anticancer agents, viz., gemcitabine (GEM) and methotrexate (MTX), to the distal ends of a long-circulating poly(ethylene glycol) (PEG...

  10. Macromolecular Stabilization by Excluded Cosolutes: Mean Field Theory of Crowded Solutions.

    Science.gov (United States)

    Sapir, Liel; Harries, Daniel

    2015-07-14

    We propose a mean field theory to account for the experimentally determined temperature dependence of protein stabilization that emerges in solutions crowded by preferentially excluded cosolutes. Based on regular solution theory and employing the Flory-Huggins approximation, our model describes cosolutes in terms of their size, and two temperature-dependent microscopic parameters that correspond to macromolecule-cosolute and bulk solution interactions. The theory not only predicts a "depletion force" that can account for the experimentally observed stabilization of protein folding or association in the presence of excluded cosolutes but also predicts the full range of associated entropic and enthalpic components. Remarkably, depending on cosolute identity and in accordance with experiments, the theory describes entropically as well as enthalpically dominated depletion forces, even those disfavored by entropy. This emerging depletion attraction cannot be simply linked to molecular volumes. Instead, the relevant parameter is an effective volume that represents an interplay between solvent, cosolute, and macromolecular interactions. We demonstrate that the apparent depletion free energy is often accompanied by significant yet compensating entropy and enthalpy terms that, although having a net zero contribution to stabilization, can obscure the underlying molecular mechanism. This study underscores the importance of including often-neglected free energy terms that correspond to solvent-cosolute and cosolute-macromolecule interactions, which for most typical cosolutes are expected to be temperature dependent. We propose that experiments specifically aimed at resolving the temperature-dependence of cosolute exclusion from macromolecular surfaces should help reveal the full range of the underlying molecular mechanisms of the depletion force.

  11. Optimization of selective inversion recovery magnetization transfer imaging for macromolecular content mapping in the human brain.

    Science.gov (United States)

    Dortch, Richard D; Bagnato, Francesca; Gochberg, Daniel F; Gore, John C; Smith, Seth A

    2018-03-24

    To optimize a selective inversion recovery (SIR) sequence for macromolecular content mapping in the human brain at 3.0T. SIR is a quantitative method for measuring magnetization transfer (qMT) that uses a low-power, on-resonance inversion pulse. This results in a biexponential recovery of free water signal that can be sampled at various inversion/predelay times (t I/ t D ) to estimate a subset of qMT parameters, including the macromolecular-to-free pool-size-ratio (PSR), the R 1 of free water (R 1f ), and the rate of MT exchange (k mf ). The adoption of SIR has been limited by long acquisition times (≈4 min/slice). Here, we use Cramér-Rao lower bound theory and data reduction strategies to select optimal t I /t D combinations to reduce imaging times. The schemes were experimentally validated in phantoms, and tested in healthy volunteers (N = 4) and a multiple sclerosis patient. Two optimal sampling schemes were determined: (i) a 5-point scheme (k mf estimated) and (ii) a 4-point scheme (k mf assumed). In phantoms, the 5/4-point schemes yielded parameter estimates with similar SNRs as our previous 16-point scheme, but with 4.1/6.1-fold shorter scan times. Pair-wise comparisons between schemes did not detect significant differences for any scheme/parameter. In humans, parameter values were consistent with published values, and similar levels of precision were obtained from all schemes. Furthermore, fixing k mf reduced the sensitivity of PSR to partial-volume averaging, yielding more consistent estimates throughout the brain. qMT parameters can be robustly estimated in ≤1 min/slice (without independent measures of ΔB 0 , B1+, and T 1 ) when optimized t I -t D combinations are selected. © 2018 International Society for Magnetic Resonance in Medicine.

  12. PURY: a database of geometric restraints of hetero compounds for refinement in complexes with macromolecular structures.

    Science.gov (United States)

    Andrejasic, Miha; Praaenikar, Jure; Turk, Dusan

    2008-11-01

    The number and variety of macromolecular structures in complex with ;hetero' ligands is growing. The need for rapid delivery of correct geometric parameters for their refinement, which is often crucial for understanding the biological relevance of the structure, is growing correspondingly. The current standard for describing protein structures is the Engh-Huber parameter set. It is an expert data set resulting from selection and analysis of the crystal structures gathered in the Cambridge Structural Database (CSD). Clearly, such a manual approach cannot be applied to the vast and ever-growing number of chemical compounds. Therefore, a database, named PURY, of geometric parameters of chemical compounds has been developed, together with a server that accesses it. PURY is a compilation of the whole CSD. It contains lists of atom classes and bonds connecting them, as well as angle, chirality, planarity and conformation parameters. The current compilation is based on CSD 5.28 and contains 1978 atom classes and 32,702 bonding, 237,068 angle, 201,860 dihedral and 64,193 improper geometric restraints. Analysis has confirmed that the restraints from the PURY database are suitable for use in macromolecular crystal structure refinement and should be of value to the crystallographic community. The database can be accessed through the web server http://pury.ijs.si/, which creates topology and parameter files from deposited coordinates in suitable forms for the refinement programs MAIN, CNS and REFMAC. In the near future, the server will move to the CSD website http://pury.ccdc.cam.ac.uk/.

  13. Macromolecular composition of terrestrial and marine organic matter in sediments across the East Siberian Arctic Shelf

    Science.gov (United States)

    Sparkes, Robert B.; Doğrul Selver, Ayça; Gustafsson, Örjan; Semiletov, Igor P.; Haghipour, Negar; Wacker, Lukas; Eglinton, Timothy I.; Talbot, Helen M.; van Dongen, Bart E.

    2016-10-01

    Mobilisation of terrestrial organic carbon (terrOC) from permafrost environments in eastern Siberia has the potential to deliver significant amounts of carbon to the Arctic Ocean, via both fluvial and coastal erosion. Eroded terrOC can be degraded during offshore transport or deposited across the wide East Siberian Arctic Shelf (ESAS). Most studies of terrOC on the ESAS have concentrated on solvent-extractable organic matter, but this represents only a small proportion of the total terrOC load. In this study we have used pyrolysis-gas chromatography-mass spectrometry (py-GCMS) to study all major groups of macromolecular components of the terrOC; this is the first time that this technique has been applied to the ESAS. This has shown that there is a strong offshore trend from terrestrial phenols, aromatics and cyclopentenones to marine pyridines. There is good agreement between proportion phenols measured using py-GCMS and independent quantification of lignin phenol concentrations (r2 = 0.67, p radiocarbon data for bulk OC (14COC) which, when coupled with previous measurements, allows us to produce the most comprehensive 14COC map of the ESAS to date. Combining the 14COC and py-GCMS data suggests that the aromatics group of compounds is likely sourced from old, aged terrOC, in contrast to the phenols group, which is likely sourced from modern woody material. We propose that an index of the relative proportions of phenols and pyridines can be used as a novel terrestrial vs. marine proxy measurement for macromolecular organic matter. Principal component analysis found that various terrestrial vs. marine proxies show different patterns across the ESAS, and it shows that multiple river-ocean transects of surface sediments transition from river-dominated to coastal-erosion-dominated to marine-dominated signatures.

  14. Spontaneous oscillations in microfluidic networks

    Science.gov (United States)

    Case, Daniel; Angilella, Jean-Regis; Motter, Adilson

    2017-11-01

    Precisely controlling flows within microfluidic systems is often difficult which typically results in systems being heavily reliant on numerous external pumps and computers. Here, I present a simple microfluidic network that exhibits flow rate switching, bistablity, and spontaneous oscillations controlled by a single pressure. That is, by solely changing the driving pressure, it is possible to switch between an oscillating and steady flow state. Such functionality does not rely on external hardware and may even serve as an on-chip memory or timing mechanism. I use an analytic model and rigorous fluid dynamics simulations to show these results.

  15. General features of spontaneous baryogenesis

    Science.gov (United States)

    Arbuzova, Elena

    2017-04-01

    The classical version of spontaneous baryogenesis is studied in details. It is shown that the relation between the time derivative of the (pseudo)goldstone field and the baryonic chemical potential essentially depends upon the representation chosen for the fermionic fields with non-zero baryonic number (quarks). The kinetic equation, used for the calculations of the cosmological baryon asymmetry, is generalized to the case of non-stationary background. The effects of the finite interval of the integration over time are also included into consideration.

  16. Spontaneous osteonecrosis of the knee

    Energy Technology Data Exchange (ETDEWEB)

    Kattapuram, Taj M. [Department of Radiology, Massachusetts General Hospital (United States); Kattapuram, Susan V. [Department of Radiology, Massachusetts General Hospital (United States)], E-mail: skattapuram@partners.org

    2008-07-15

    Spontaneous osteonecrosis of the knee presents with acute onset of severe, pain in elderly patients, usually female and usually without a history of trauma. Originally described as idiopathic osteonecrosis, the exact etiology is still debated. Evidence suggests that an acute fracture occurs as a result of chronic stress or minor trauma to a weakened subchondral bone plate. The imaging characteristics on MR reflect the age of the lesion and the symptoms. More appropriate terminology may be ' subchondral insufficiency fracture of the knee' or 'focal subchondral osteonecrosis'.

  17. Speech Entrainment Compensates for Broca's Area Damage

    Science.gov (United States)

    Fridriksson, Julius; Basilakos, Alexandra; Hickok, Gregory; Bonilha, Leonardo; Rorden, Chris

    2015-01-01

    Speech entrainment (SE), the online mimicking of an audiovisual speech model, has been shown to increase speech fluency in patients with Broca's aphasia. However, not all individuals with aphasia benefit from SE. The purpose of this study was to identify patterns of cortical damage that predict a positive response SE's fluency-inducing effects. Forty-four chronic patients with left hemisphere stroke (15 female) were included in this study. Participants completed two tasks: 1) spontaneous speech production, and 2) audiovisual SE. Number of different words per minute was calculated as a speech output measure for each task, with the difference between SE and spontaneous speech conditions yielding a measure of fluency improvement. Voxel-wise lesion-symptom mapping (VLSM) was used to relate the number of different words per minute for spontaneous speech, SE, and SE-related improvement to patterns of brain damage in order to predict lesion locations associated with the fluency-inducing response to speech entrainment. Individuals with Broca's aphasia demonstrated a significant increase in different words per minute during speech entrainment versus spontaneous speech. A similar pattern of improvement was not seen in patients with other types of aphasia. VLSM analysis revealed damage to the inferior frontal gyrus predicted this response. Results suggest that SE exerts its fluency-inducing effects by providing a surrogate target for speech production via internal monitoring processes. Clinically, these results add further support for the use of speech entrainment to improve speech production and may help select patients for speech entrainment treatment. PMID:25989443

  18. Superhydrophobic hybrid membranes by grafting arc-like macromolecular bridges on graphene sheets: Synthesis, characterization and properties

    Science.gov (United States)

    Mo, Zhao-Hua; Luo, Zheng; Huang, Qiang; Deng, Jian-Ping; Wu, Yi-Xian

    2018-05-01

    Grafting single end-tethered polymer chains on the surface of graphene is a conventional way to modify the surface properties of graphene oxide. However, grafting arc-like macromolecular bridges on graphene surfaces has been barely reported. Herein, a novel arc-like polydimethylsiloxane (PDMS) macromolecular bridges grafted graphene sheets (GO-g-Arc PDMS) was successfully synthesized via a confined interface reaction at 90 °C. Both the hydrophilic α- and ω-amino groups of linear hydrophobic NH2-PDMS-NH2 macromolecular chains rapidly reacted with epoxy and carboxyl groups on the surfaces of graphene oxide in water suspension to form arc-like PDMS macromolecular bridges on graphene sheets. The grafting density of arc-like PDMS bridges on graphene sheets can reach up to 0.80 mmol g-1 or 1.32 arc-like bridges per nm2 by this confined interface reaction. The water contact angle (WCA) of the hybrid membrane could be increased with increasing both the grafting density and content of covalent arc-like bridges architecture. The superhydrophobic hybrid membrane with a WCA of 153.4° was prepared by grinding of the above arc-like PDMS bridges grafted graphene hybrid, dispersing in ethanol and filtrating by organic filter membrane. This superhydrophobic hybrid membrane shows good self-cleaning and complete oil-water separation properties, which provides potential applications in anticontamination coating and oil-water separation. To the best of our knowledge, this is the first report on the synthesis of functional hybrid membranes by grafting arc-like PDMS macromolecular bridges on graphene sheets via a confined interface reaction.

  19. Clinical pitfalls in misoprostol-based medical management of first-trimester induced and presumed spontaneous abortion.

    Science.gov (United States)

    Wax, Joseph R; Conroy, Kelley; Pinette, Michael G; Litton, Christian; Cartin, Angelina

    2017-12-28

    When administered inappropriately, first-trimester misoprostol management of induced or spontaneous abortion can result in loss or damage of a continuing pregnancy. Despite these serious consequences, such misoprostol exposures continue to occur. Unfortunately, contributing factors and preventive measures receive little attention. We describe the cases of 4 women in whom misoprostol was inappropriately administered during management of induced and presumed spontaneous abortion. In each case, careful adherence to published clinical guidance could have avoided the exposures. © 2017 Wiley Periodicals, Inc.

  20. Radiological evaluation of spontaneous pneumoperitoneum

    International Nuclear Information System (INIS)

    Kim, H. S.; Kim, J. D.; Rhee, H. S.

    1982-01-01

    112 cases of spontaneous penumoperitoneum, the causes of which were confirmed by clinical and surgical procedure at Presbyterian Medical Center from January, 1977 to July, 1981 were reviewed radiologically. The results were as follows: 1. Perforation of duodenal ulcer (46/112: 41.1%), stomach ulcer (22/112: 19.6%), and stomach cancer (11/112: 9.8%) were the three most common causes of spontaneous penumoperitoneum. These were 70.5% of all causes. 2. The most common site of free gas was both subdiaphragmatic areas (46: 41.1%). Others were Rt. subdiaphragmatic only (31: 27.7%), both subdiaphragmatic with subhepatic (16: 14.3%), Rt. subdiaphragmatic with subhepatic (7: 6.2%), Rt. subdiaphragmatic only (5: 4.4%), diffuse in abdomen (4: 3.6%), and subhepatic only (3: 2.7%). So 92.0% (103/112) were located in RUQ. 3. The radiological shape of free gas was classified: crescent (52: 46.4%) of small amount; half-moon (21: 18.8%) of moderate amount; large or diffuse (39: 34.8%) of large amount.4. The age between 31 and 60 occupied 69.1% (77/112), and male was predominant (5.2 times). 5. The patient's position showing free air most frequently was erect

  1. A Case of Multiple Spontaneous Keloid Scars

    Directory of Open Access Journals (Sweden)

    Abdulhadi Jfri

    2015-07-01

    Full Text Available Keloid scars result from an abnormal healing response to cutaneous injury or inflammation that extends beyond the borders of the original wound. Spontaneous keloid scars forming in the absence of any previous trauma or surgical procedure are rare. Certain syndromes have been associated with this phenomenon, and few reports have discussed the evidence of single spontaneous keloid scar, which raises the question whether they are really spontaneous. Here, we present a 27-year-old mentally retarded single female with orbital hypertelorism, broad nasal bridge, repaired cleft lip and high-arched palate who presented with progressive multiple spontaneous keloid scars in different parts of her body which were confirmed histologically by the presence of typical keloidal collagen. This report supports the fact that keloid scars can appear spontaneously and are possibly linked to a genetic factor. Furthermore, it describes a new presentation of spontaneous keloid scars in the form of multiple large lesions in different sites of the body.

  2. Spontaneity of communication in individuals with autism.

    Science.gov (United States)

    Chiang, Hsu-Min; Carter, Mark

    2008-04-01

    This article provides an examination of issues related to spontaneity of communication in children with autism. Deficits relating to spontaneity or initiation are frequently reported in individuals with autism, particularly in relation to communication and social behavior. Nevertheless, spontaneity is not necessarily clearly conceptualized or measured. Several approaches to conceptualization of communicative spontaneity are examined with a particular focus on the continuum model and how it might be practically applied. A range of possible explanations for deficits in spontaneity of communication in children with autism is subsequently explored, including external factors (highly structured teaching programs, failure to systematically instruct for spontaneity) and intrinsic characteristics (intellectual disability, stimulus overselectivity, weak central coherence). Possible implications for future research are presented.

  3. Spontaneous cryptococcal peritonitis in cirrhotic patients.

    Directory of Open Access Journals (Sweden)

    Sungkanuparph S

    2002-07-01

    Full Text Available Spontaneous bacterial peritonitis is a common complication in patients with cirrhosis and ascites. However, spontaneous peritonitis caused by Cryptococcus neoformans is uncommon. Delayed diagnosis of cryptococcal peritonitis often results in death. We describe three cases of spontaneous cryptococcal peritonitis in patients with decompensated cirrhosis. One case had associated symptomatic human immunodeficiency virus infection. Clinical awareness of this entity may lead to the early diagnosis and proper treatment.

  4. Spontaneous Intracranial Hypotension without Orthostatic Headache

    Directory of Open Access Journals (Sweden)

    Tülay Kansu

    2009-03-01

    Full Text Available We report 2 cases of spontaneous intracranial hypotension that presented with unilateral abducens nerve palsy, without orthostatic headache. While sixth nerve palsies improved without any intervention, subdural hematoma was detected with magnetic resonance imaging. We conclude that headache may be absent in spontaneous intracranial hypotension and spontaneous improvement of sixth nerve palsy can occur, even after the development of a subdural hematoma

  5. Spontaneous renal hematoma - a case report

    International Nuclear Information System (INIS)

    Obrzut, M.; Obrzut, M.; Homa, J.; Obrzut, B.

    2006-01-01

    Spontaneous pararenal hematoma is a rare pathology most frequently coexisting with renal tumours, vascular anomalies and inflammatory processes. In some cases one cannot establish its etiology. The paper describes a case of a 58-year-old man with a spontaneous pararenal hematoma and presents a diagnostic algorithm. Ultrasonography and CT play an important role in diagnostics of spontaneous pararenal haemorrhages. These methods enable a precise evaluation of size and location of hematoma and its evolution. (author)

  6. Biomarkers of spontaneous preterm birth

    DEFF Research Database (Denmark)

    Polettini, Jossimara; Cobo, Teresa; Kacerovsky, Marian

    2017-01-01

    predictors of pregnancy outcome. This systematic review was conducted to synthesize the knowledge on PTB biomarkers identified using multiplex analysis. Three electronic databases (PubMed, EMBASE and Web of Science) were searched for studies in any language reporting the use of multiplex assays for maternal......Despite decades of research on risk indicators of spontaneous preterm birth (PTB), reliable biomarkers are still not available to screen or diagnose high-risk pregnancies. Several biomarkers in maternal and fetal compartments have been mechanistically linked to PTB, but none of them are reliable......) followed by MIP-1β, GM-CSF, Eotaxin, and TNF-RI (two studies) were reported more than once in maternal serum. However, results could not be combined due to heterogeneity in type of sample, study population, assay, and analysis methods. By this systematic review, we conclude that multiplex assays...

  7. Spontaneous Strategies in Innovation Networks

    DEFF Research Database (Denmark)

    Plesner, Ursula; Husted, Emil Krastrup

    and a site ontology, we show how physical sites and objects become constitutive of the inside of virtual worlds through innovation processes. This argument is in line with ANT’s perspective on strategy, where sites and objects are considered a strategically relevant resource in the innovation process...... of materiality in relation to the organization and structuring of virtual worlds. We examine various innovation processes in five Danish entrepreneurial companies where actors continuously struggle to stabilize virtual worlds as platforms for professional communication. With inspiration from actor-network theory....... Empirically, the analysis is founded on descriptive accounts from the five entrepreneurs. By highlighting the spontaneous strategies described by actors, we show how sites and objects are actively used as an element in their strategy, and also how the sites and objects end up facilitating new ways of thinking...

  8. Recurrent spontaneous attacks of dizziness.

    Science.gov (United States)

    Lempert, Thomas

    2012-10-01

    This article describes the common causes of recurrent vertigo and dizziness that can be diagnosed largely on the basis of history. Ninety percent of spontaneous recurrent vertigo and dizziness can be explained by six disorders: (1) Ménière disease is characterized by vertigo attacks, lasting 20 minutes to several hours, with concomitant hearing loss, tinnitus, and aural fullness. Aural symptoms become permanent during the course of the disease. (2) Attacks of vestibular migraine may last anywhere from minutes to days. Most patients have a previous history of migraine headaches, and many experience migraine symptoms during the attack. (3) Vertebrobasilar TIAs affect older adults with vascular risk factors. Most attacks last less than 1 hour and are accompanied by other symptoms from the posterior circulation territory. (4) Vestibular paroxysmia is caused by vascular compression of the eighth cranial nerve. It manifests itself with brief attacks of vertigo that recur many times per day, sometimes with concomitant cochlear symptoms. (5) Orthostatic hypotension causes brief episodes of dizziness lasting seconds to a few minutes after standing up and is relieved by sitting or lying down. In older adults, it may be accompanied by supine hypertension. (6) Panic attacks usually last minutes, occur in specific situations, and are accompanied by choking, palpitations, tremor, heat, and anxiety. Less common causes of spontaneous recurrent vertigo and dizziness include perilymph fistula, superior canal dehiscence, autoimmune inner ear disease, otosclerosis, cardiac arrhythmia, and medication side effects. Neurologists need to venture into otolaryngology, internal medicine, and psychiatry to master the differential diagnosis of recurrent dizziness.

  9. Crows spontaneously exhibit analogical reasoning.

    Science.gov (United States)

    Smirnova, Anna; Zorina, Zoya; Obozova, Tanya; Wasserman, Edward

    2015-01-19

    Analogical reasoning is vital to advanced cognition and behavioral adaptation. Many theorists deem analogical thinking to be uniquely human and to be foundational to categorization, creative problem solving, and scientific discovery. Comparative psychologists have long been interested in the species generality of analogical reasoning, but they initially found it difficult to obtain empirical support for such thinking in nonhuman animals (for pioneering efforts, see [2, 3]). Researchers have since mustered considerable evidence and argument that relational matching-to-sample (RMTS) effectively captures the essence of analogy, in which the relevant logical arguments are presented visually. In RMTS, choice of test pair BB would be correct if the sample pair were AA, whereas choice of test pair EF would be correct if the sample pair were CD. Critically, no items in the correct test pair physically match items in the sample pair, thus demanding that only relational sameness or differentness is available to support accurate choice responding. Initial evidence suggested that only humans and apes can successfully learn RMTS with pairs of sample and test items; however, monkeys have subsequently done so. Here, we report that crows too exhibit relational matching behavior. Even more importantly, crows spontaneously display relational responding without ever having been trained on RMTS; they had only been trained on identity matching-to-sample (IMTS). Such robust and uninstructed relational matching behavior represents the most convincing evidence yet of analogical reasoning in a nonprimate species, as apes alone have spontaneously exhibited RMTS behavior after only IMTS training. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. AutoDrug: fully automated macromolecular crystallography workflows for fragment-based drug discovery

    International Nuclear Information System (INIS)

    Tsai, Yingssu; McPhillips, Scott E.; González, Ana; McPhillips, Timothy M.; Zinn, Daniel; Cohen, Aina E.; Feese, Michael D.; Bushnell, David; Tiefenbrunn, Theresa; Stout, C. David; Ludaescher, Bertram; Hedman, Britt; Hodgson, Keith O.; Soltis, S. Michael

    2013-01-01

    New software has been developed for automating the experimental and data-processing stages of fragment-based drug discovery at a macromolecular crystallography beamline. A new workflow-automation framework orchestrates beamline-control and data-analysis software while organizing results from multiple samples. AutoDrug is software based upon the scientific workflow paradigm that integrates the Stanford Synchrotron Radiation Lightsource macromolecular crystallography beamlines and third-party processing software to automate the crystallography steps of the fragment-based drug-discovery process. AutoDrug screens a cassette of fragment-soaked crystals, selects crystals for data collection based on screening results and user-specified criteria and determines optimal data-collection strategies. It then collects and processes diffraction data, performs molecular replacement using provided models and detects electron density that is likely to arise from bound fragments. All processes are fully automated, i.e. are performed without user interaction or supervision. Samples can be screened in groups corresponding to particular proteins, crystal forms and/or soaking conditions. A single AutoDrug run is only limited by the capacity of the sample-storage dewar at the beamline: currently 288 samples. AutoDrug was developed in conjunction with RestFlow, a new scientific workflow-automation framework. RestFlow simplifies the design of AutoDrug by managing the flow of data and the organization of results and by orchestrating the execution of computational pipeline steps. It also simplifies the execution and interaction of third-party programs and the beamline-control system. Modeling AutoDrug as a scientific workflow enables multiple variants that meet the requirements of different user groups to be developed and supported. A workflow tailored to mimic the crystallography stages comprising the drug-discovery pipeline of CoCrystal Discovery Inc. has been deployed and successfully

  11. Macromolecular composition of terrestrial and marine organic matter in sediments across the East Siberian Arctic Shelf

    Directory of Open Access Journals (Sweden)

    R. B. Sparkes

    2016-10-01

    Full Text Available Mobilisation of terrestrial organic carbon (terrOC from permafrost environments in eastern Siberia has the potential to deliver significant amounts of carbon to the Arctic Ocean, via both fluvial and coastal erosion. Eroded terrOC can be degraded during offshore transport or deposited across the wide East Siberian Arctic Shelf (ESAS. Most studies of terrOC on the ESAS have concentrated on solvent-extractable organic matter, but this represents only a small proportion of the total terrOC load. In this study we have used pyrolysis–gas chromatography–mass spectrometry (py-GCMS to study all major groups of macromolecular components of the terrOC; this is the first time that this technique has been applied to the ESAS. This has shown that there is a strong offshore trend from terrestrial phenols, aromatics and cyclopentenones to marine pyridines. There is good agreement between proportion phenols measured using py-GCMS and independent quantification of lignin phenol concentrations (r2 = 0.67, p < 0.01, n = 24. Furfurals, thought to represent carbohydrates, show no offshore trend and are likely found in both marine and terrestrial organic matter. We have also collected new radiocarbon data for bulk OC (14COC which, when coupled with previous measurements, allows us to produce the most comprehensive 14COC map of the ESAS to date. Combining the 14COC and py-GCMS data suggests that the aromatics group of compounds is likely sourced from old, aged terrOC, in contrast to the phenols group, which is likely sourced from modern woody material. We propose that an index of the relative proportions of phenols and pyridines can be used as a novel terrestrial vs. marine proxy measurement for macromolecular organic matter. Principal component analysis found that various terrestrial vs. marine proxies show different patterns across the ESAS, and it shows that multiple river–ocean transects of surface sediments transition from river-dominated to

  12. Stabiliteit spontane taal bij chronische milde afasie

    NARCIS (Netherlands)

    Wolthuis, Nienke; Mendez Orellana, Carolina; Nouwens, Femke; Jonkers, Roel; Visch-Brink, Evy; Bastiaanse, Roelien

    2014-01-01

    In aphasia, an analysis of spontaneous speech provides opportunities to establish the linguistic and communicative abilities, to create suitable therapy plans and to measure language progress. The current study investigated the stability of spontaneous speech within an interview of ten mild aphasic

  13. Spontaneously broken abelian gauge invariant supersymmetric model

    International Nuclear Information System (INIS)

    Mainland, G.B.; Tanaka, K.

    A model is presented that is invariant under an Abelian gauge transformation and a modified supersymmetry transformation. This model is broken spontaneously, and the interplay between symmetry breaking, Goldstone particles, and mass breaking is studied. In the present model, spontaneously breaking the Abelian symmetry of the vacuum restores the invariance of the vacuum under a modified supersymmetry transformation. (U.S.)

  14. Spontaneous Achilles tendon rupture in alkaptonuria | Mohammed ...

    African Journals Online (AJOL)

    Spontaneous Achilles tendon ruptures are uncommon. We present a 46-year-old man with spontaneous Achilles tendon rupture due to ochronosis. To our knowledge, this has not been previously reported in Sudan literature. The tendon of the reported patient healed well after debridement and primary repairs.

  15. Spontaneous rupture of choledochal cyst: case report

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Ho Seob; Nam, Kyung Jin; Lee, Jin Hwa; Kim, Chan Sung; Choi, Jong Cheol; Oh, Jong Young [Dong-a University College of Medicine, Pusan (Korea, Republic of)

    2002-11-01

    Spontaneous rupture of a choledochal cyst leading to biliary peritonitis is a rare complication which can be fatal if not promptly diagnosed. The authors report the ultrasound and CT findings of two cases of spontaneous choledochal cystic rupture and the biliary peritonitis which ensued.

  16. Spontaneity and Equilibrium II: Multireaction Systems

    Science.gov (United States)

    Raff, Lionel M.

    2014-01-01

    The thermodynamic criteria for spontaneity and equilibrium in multireaction systems are developed and discussed. When N reactions are occurring simultaneously, it is shown that G and A will depend upon N independent reaction coordinates, ?a (a = 1,2, ..., N), in addition to T and p for G or T and V for A. The general criteria for spontaneity and…

  17. Damage analysis: damage function development and application

    International Nuclear Information System (INIS)

    The derivation and application of damage functions, including recent developments for the U.S. LMFBR and CTR programs, is reviewed. A primary application of damage functions is in predicting component life expectancies; i.e., the fluence required in a service spectrum to attain a specified design property change. An important part of the analysis is the estimation of the uncertainty in such fluence limit predictions. The status of standardizing the procedures for the derivation and application of damage functions is discussed. Improvements in several areas of damage function development are needed before standardization can be completed. These include increasing the quantity and quality of the data used in the analysis, determining the limitations of the analysis due to the presence of multiple damage mechanisms, and finally, testing of damage function predictions against data obtained from material surveillance programs in operating thermal and fast reactors. 23 references. (auth)

  18. Material Induced Anisotropic Damage

    NARCIS (Netherlands)

    Niazi, Muhammad Sohail; Wisselink, H.H.; Meinders, Vincent T.; van den Boogaard, Antonius H.; Hora, P.

    2012-01-01

    The anisotropy in damage can be driven by two different phenomena; anisotropic defor-mation state named Load Induced Anisotropic Damage (LIAD) and anisotropic (shape and/or distribution) second phase particles named Material Induced Anisotropic Damage (MIAD). Most anisotropic damage models are based

  19. Early pregnancy angiogenic markers and spontaneous abortion

    DEFF Research Database (Denmark)

    Andersen, Louise B; Dechend, Ralf; Karumanchi, S Ananth

    2016-01-01

    BACKGROUND: Spontaneous abortion is the most commonly observed adverse pregnancy outcome. The angiogenic factors soluble Fms-like kinase 1 and placental growth factor are critical for normal pregnancy and may be associated to spontaneous abortion. OBJECTIVE: We investigated the association between...... maternal serum concentrations of soluble Fms-like kinase 1 and placental growth factor, and subsequent spontaneous abortion. STUDY DESIGN: In the prospective observational Odense Child Cohort, 1676 pregnant women donated serum in early pregnancy, gestational week ..., interquartile range 71-103). Concentrations of soluble Fms-like kinase 1 and placental growth factor were determined with novel automated assays. Spontaneous abortion was defined as complete or incomplete spontaneous abortion, missed abortion, or blighted ovum

  20. Beamline AR-NW12A: high-throughput beamline for macromolecular crystallography at the Photon Factory.

    Science.gov (United States)

    Chavas, L M G; Matsugaki, N; Yamada, Y; Hiraki, M; Igarashi, N; Suzuki, M; Wakatsuki, S

    2012-05-01

    AR-NW12A is an in-vacuum undulator beamline optimized for high-throughput macromolecular crystallography experiments as one of the five macromolecular crystallography (MX) beamlines at the Photon Factory. This report provides details of the beamline design, covering its optical specifications, hardware set-up, control software, and the latest developments for MX experiments. The experimental environment presents state-of-the-art instrumentation for high-throughput projects with a high-precision goniometer with an adaptable goniometer head, and a UV-light sample visualization system. Combined with an efficient automounting robot modified from the SSRL SAM system, a remote control system enables fully automated and remote-access X-ray diffraction experiments.

  1. The 2D Structure of the T. brucei Preedited RPS12 mRNA Is Not Affected by Macromolecular Crowding

    Directory of Open Access Journals (Sweden)

    W.-Matthias Leeder

    2017-01-01

    Full Text Available Mitochondrial transcript maturation in African trypanosomes requires RNA editing to convert sequence-deficient pre-mRNAs into translatable mRNAs. The different pre-mRNAs have been shown to adopt highly stable 2D folds; however, it is not known whether these structures resemble the in vivo folds given the extreme “crowding” conditions within the mitochondrion. Here, we analyze the effects of macromolecular crowding on the structure of the mitochondrial RPS12 pre-mRNA. We use high molecular mass polyethylene glycol as a macromolecular cosolute and monitor the structure of the RNA globally and with nucleotide resolution. We demonstrate that crowding has no impact on the 2D fold and we conclude that the MFE structure in dilute solvent conditions represents a good proxy for the folding of the pre-mRNA in its mitochondrial solvent context.

  2. Distribution and enzymatic activity of heterotrophic bacteria decomposing selected macromolecular compounds in a Baltic Sea sandy beach

    Science.gov (United States)

    Podgórska, B.; Mudryk, Z. J.

    2003-03-01

    The potential capability to decompose macromolecular compounds, and the level of extracellular enzyme activities were determined in heterotrophic bacteria isolated from a sandy beach in Sopot on the Southern Baltic Sea coast. Individual isolates were capable of hydrolysing a wide spectrum of organic macromolecular compounds. Lipids, gelatine, and DNA were hydrolyzed most efficiently. Only a very small percentage of strains were able to decompose cellulose, and no pectinolytic bacteria were found. Except for starch-hydrolysis, no significant differences in the intensity of organic compound decomposition were recorded between horizontal and vertical profiles of the studied beach. Of all the studied extracellular enzymes, alkaline phosphatase, esterase lipase, and leucine acrylaminidase were most active; in contrast, the activity α-fucosidase, α-galactosidase and β-glucouronidase was the weakest. The level of extracellular enzyme activity was similar in both sand layers.

  3. The (perceived) meaning of spontaneous thoughts.

    Science.gov (United States)

    Morewedge, Carey K; Giblin, Colleen E; Norton, Michael I

    2014-08-01

    Spontaneous thoughts, the output of a broad category of uncontrolled and inaccessible higher order mental processes, arise frequently in everyday life. The seeming randomness by which spontaneous thoughts arise might give people good reason to dismiss them as meaningless. We suggest that it is precisely the lack of control over and access to the processes by which they arise that leads people to perceive spontaneous thoughts as revealing meaningful self-insight. Consequently, spontaneous thoughts potently influence judgment. A series of experiments provides evidence supporting two hypotheses. First, we hypothesize that the more a thought is perceived to be spontaneous, the more it is perceived to provide meaningful self-insight. Participants perceived more spontaneous kinds of thought (e.g., intuition) to reveal greater self-insight than did more controlled kinds of thought in Study 1 (e.g., deliberation). In Studies 2 and 3, participants perceived thoughts with the same content and target to reveal greater self-insight when spontaneously rather than deliberately generated (i.e., childhood memories and impressions formed). Second, we hypothesize that the greater self-insight attributed to thoughts that are (perceived to be) spontaneous leads those thoughts to more potently influence judgment. Participants felt more sexually attracted to an attractive person whom they thought of spontaneously than deliberately in Study 4, and reported their commitment to a current romantic relationship would be more affected by the spontaneous rather than deliberate recollection of a good or bad experience with their romantic partner in Study 5. PsycINFO Database Record (c) 2014 APA, all rights reserved.

  4. Macromolecular composition of a Cellulomonas sp. cultivated in continuous culture under glucose and zinc limitation.

    Science.gov (United States)

    Summers, R J; Srinivasan, V R

    1979-01-01

    The mutant strain of Cellulomonas sp. (ATCC 21399) was cultivated under glucose and zinc limitation at a variety of growth rates in continuous culture. The growth characteristics and macromolecular composition of the population varied with the limitation imposed and the growth rate. Glucose- and zinc-limited cultures maintained a constant relative protein content. The relative ribonucleic acid content increased, whereas the carbohydrate and deoxyribonucleic acid contents decreased with an increase in the population growth rate in glucose-limited cultures. Free unbound lipid remained constant. The maximum population growth rate in zinc-limited cultures was directly proportional to the zinc concentration and demonstrated a traditional steady-state function. The nucleic acid content increased with increased growth rate; however, the relative nucleic acid content was significantly depressed when compared to glucose limited cells. This manner of cultivation may prove to be a useful tool for the production of single cell protein with lowered nucleic acid content and the elucidation of micronutrient involvement in growth-related processes. PMID:114114

  5. Effects of sound exposure on the growth and intracellular macromolecular synthesis of E. coli k-12.

    Science.gov (United States)

    Gu, Shaobin; Zhang, Yongzhu; Wu, Ying

    2016-01-01

    Microbes, as one of the primary producers of the biosphere, play an important role in ecosystems. Exploring the mechanism of adaptation and resistance of microbial population to various environmental factors has come into focus in the fields of modern microbial ecology and molecular ecology. However, facing the increasingly serious problem of acoustic pollution, very few efforts have been put forth into studying the relation of single cell organisms and sound field exposure. Herein, we studied the biological effects of sound exposure on the growth of E. coli K-12 with different acoustic parameters. The effects of sound exposure on the intracellular macromolecular synthesis and cellular morphology of E. coli K-12 were also analyzed and discussed. Experimental results indicated that E. coli K-12 exposed to sound waves owned a higher biomass and a faster specific growth rate compared to the control group. Also, the average length of E. coli K-12 cells increased more than 27.26%. The maximum biomass and maximum specific growth rate of the stimulation group by 8000 Hz, 80dB sound wave was about 1.7 times and 2.5 times that of the control group, respectively. Moreover, it was observed that E. coli K-12 can respond rapidly to sound stress at both the transcriptional and posttranscriptional levels by promoting the synthesis of intracellular RNA and total protein. Some potential mechanisms may be involved in the responses of bacterial cells to sound stress.

  6. Effects of sound exposure on the growth and intracellular macromolecular synthesis of E. coli k-12

    Directory of Open Access Journals (Sweden)

    Shaobin Gu

    2016-04-01

    Full Text Available Microbes, as one of the primary producers of the biosphere, play an important role in ecosystems. Exploring the mechanism of adaptation and resistance of microbial population to various environmental factors has come into focus in the fields of modern microbial ecology and molecular ecology. However, facing the increasingly serious problem of acoustic pollution, very few efforts have been put forth into studying the relation of single cell organisms and sound field exposure. Herein, we studied the biological effects of sound exposure on the growth of E. coli K-12 with different acoustic parameters. The effects of sound exposure on the intracellular macromolecular synthesis and cellular morphology of E. coli K-12 were also analyzed and discussed. Experimental results indicated that E. coli K-12 exposed to sound waves owned a higher biomass and a faster specific growth rate compared to the control group. Also, the average length of E. coli K-12 cells increased more than 27.26%. The maximum biomass and maximum specific growth rate of the stimulation group by 8000 Hz, 80dB sound wave was about 1.7 times and 2.5 times that of the control group, respectively. Moreover, it was observed that E. coli K-12 can respond rapidly to sound stress at both the transcriptional and posttranscriptional levels by promoting the synthesis of intracellular RNA and total protein. Some potential mechanisms may be involved in the responses of bacterial cells to sound stress.

  7. Hydrolysis of macromolecular components of primary and secondary wastewater sludge by thermal hydrolytic pretreatment.

    Science.gov (United States)

    Wilson, Christopher A; Novak, John T

    2009-10-01

    A laboratory simulation of the thermal hydrolytic pretreatment (THP) process was performed on wastewater sludge, as well as key macromolecular components: proteins, lipids, and polysaccharides. Hydrolysis temperatures from 130 to 220 degrees C were investigated. The objectives of this study were to determine how and over which temperature range THP specifically affects sludge components, and whether hydrolysis temperature can be used to minimize the previously reported drawbacks of THP such as high total ammonia nitrogen (TAN) loads and the production of highly-colored recalcitrant organics. In addition, the applicability of THP to primary sludge (PS) was investigated. The breakdown of proteins, lipids, and polysaccharides was determined to be temperature dependent, and both waste activated sludge (WAS) and PS responded similarly to THP apart from intrinsic differences in lipid and protein content. Pure carbohydrate solutions were not largely converted to mono- or dimeric reducing sugar units at temperatures below 220 degrees C, however significant caramelization of starch and production of dextrose and maltose was observed to occur at 220 degrees C. Volatile fatty acid production during thermal hydrolysis was largely attributed to the breakdown of unsaturated lipids, and long-chain fatty acid production was not significant in terms of previous reports of methanogenic inhibition. Ammonia was produced from protein during thermal hydrolysis, however solids loading rather than thermal hydrolysis temperature appeared to be a more meaningful control for ammonia levels in downstream anaerobic digestion.

  8. Strategy of macromolecular grafting onto a gold substrate dedicated to protein-protein interaction measurements.

    Science.gov (United States)

    Mansuy-Schlick, V; Delage-Mourroux, R; Jouvenot, M; Boireau, W

    2006-03-15

    Many biotechnology applications use proteins immobilized on surface. For biosensor, the sensing layer is a key component interfacing the transducer and the sample. Strategies employed to activate the bidimensional surface act directly on the performance of the biosensor. In this paper we propose a novel strategy for engineered proteins self-assembly. Our original supramolecular structure allows a direct and fast covalent attachment of proteins onto bare gold substrate through a homobifunctional cross-linker, 1,4-di-([2'-pyridyldithio]propionamido)butane (DPDPB). In this work, engineered proteins and linker-protein complexes were synthesized and characterized by gel electrophoresis, chromatography and spectroscopy experiments. Macromolecular construction "DPDPB-GST tag-GEC1 protein" was conceived in order to guarantee a 2D architecture enhancing the capabilities of the target (tubulin) to recognize its partner (GEC1). Surface plasmon resonance measurements clearly showed potential of this particular self-assembled protein layer compared to a commercial immunosensor interface. At the concentrations tested, the recognition process occurs between tubulin and the immobilized GEC1; moreover enhanced binding was obtained with the home-made 2D sensing layer more than with 3D carboxymethyl dextran matrix.

  9. Heterogeneity of large macromolecular complexes revealed by 3-D cryo-EM variance analysis

    Science.gov (United States)

    Zhang, Wei; Kimmel, Marek; Spahn, Christian M.T.; Penczek, Pawel A.

    2008-01-01

    Macromolecular structure determination by cryo-electron microscopy (EM) and single particle analysis are based on the assumption that imaged molecules have identical structure. With the increased size of processed datasets it becomes apparent that many complexes coexist in a mixture of conformational states or contain flexible regions. As the cryo-EM data is collected in form of projections of imaged molecules, the information about variability of reconstructed density maps is not directly available. To address this problem, we describe a new implementation of the bootstrap resampling technique that yields estimates of voxel-by-voxel variance of a structure reconstructed from the set of its projections. We introduced a novel highly efficient reconstruction algorithm that is based on direct Fourier inversion and which incorporates correction for the transfer function of the microscope, thus extending the resolution limits of variance estimation. We also describe a validation method to determine the number of resampled volumes required to achieve stable estimate of the variance. The proposed bootstrap method was applied to a dataset of 70S ribosome complexed with tRNA and the elongation factor G. The variance map revealed regions of high variability: the L1 protein, the EF-G and the 30S head and the ratchet-like subunit rearrangement. The proposed method of variance estimation opens new possibilities for single particle analysis, by extending applicability of the technique to heterogeneous datasets of macromolecules, and to complexes with significant conformational variability. PMID:19081053

  10. MetalPDB: a database of metal sites in biological macromolecular structures.

    Science.gov (United States)

    Andreini, Claudia; Cavallaro, Gabriele; Lorenzini, Serena; Rosato, Antonio

    2013-01-01

    We present here MetalPDB (freely accessible at http://metalweb.cerm.unifi.it), a novel resource aimed at conveying the information available on the three-dimensional (3D) structures of metal-binding biological macromolecules in a consistent and effective manner. This is achieved through the systematic and automated representation of metal-binding sites in proteins and nucleic acids by way of Minimal Functional Sites (MFSs). MFSs are 3D templates that describe the local environment around the metal(s) independently of the larger context of the macromolecular structure embedding the site(s), and are the central objects of MetalPDB design. MFSs are grouped into equistructural (broadly defined as sites found in corresponding positions in similar structures) and equivalent sites (equistructural sites that contain the same metals), allowing users to easily analyse similarities and variations in metal-macromolecule interactions, and to link them to functional information. The web interface of MetalPDB allows access to a comprehensive overview of metal-containing biological structures, providing a basis to investigate the basic principles governing the properties of these systems. MetalPDB is updated monthly in an automated manner.

  11. MetalPDB in 2018: a database of metal sites in biological macromolecular structures.

    Science.gov (United States)

    Putignano, Valeria; Rosato, Antonio; Banci, Lucia; Andreini, Claudia

    2018-01-04

    MetalPDB (http://metalweb.cerm.unifi.it/) is a database providing information on metal-binding sites detected in the three-dimensional (3D) structures of biological macromolecules. MetalPDB represents such sites as 3D templates, called Minimal Functional Sites (MFSs), which describe the local environment around the metal(s) independently of the larger context of the macromolecular structure. The 2018 update of MetalPDB includes new contents and tools. A major extension is the inclusion of proteins whose structures do not contain metal ions although their sequences potentially contain a known MFS. In addition, MetalPDB now provides extensive statistical analyses addressing several aspects of general metal usage within the PDB, across protein families and in catalysis. Users can also query MetalPDB to extract statistical information on structural aspects associated with individual metals, such as preferred coordination geometries or aminoacidic environment. A further major improvement is the functional annotation of MFSs; the annotation is manually performed via a password-protected annotator interface. At present, ∼50% of all MFSs have such a functional annotation. Other noteworthy improvements are bulk query functionality, through the upload of a list of PDB identifiers, and ftp access to MetalPDB contents, allowing users to carry out in-depth analyses on their own computational infrastructure. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  12. Visualization of X-ray Beam Using CdWO4 Crystal for Macromolecular Crystallography

    Directory of Open Access Journals (Sweden)

    Kazimierz J. Gofron

    2011-12-01

    Full Text Available In synchrotron diffraction experiments, it is typically assumed that the X-ray beam at the sample position is uniform, stable and has dimensions that are controlled by the focus and slits settings. As might be expected, this process is much more complex. We present here an investigation of the properties of a synchrotron X-ray beam at the sample position. The X-ray beam is visualized with a single crystal scintillator that converts X-ray photons into visible light photons, which can be imaged using Structure Biology Center (SBC on-axis and off-axis microscope optics. The X-ray penetration is dependent on the composition of the scintillator (especially the effective Z, and X-ray energy. Several scintillators have been used to visualize X-ray beams. Here we compare CdWO4, PbWO4, Bi4Ge3O12, Y3Al5O12:Ce (YAG:Ce, and Gd2O2S:Tb (phosphor. We determined that scintillator crystals made of CdWO4 and similar high-Z materials are best suited for the energy range (7–20 keV and are most suitable for beam visualization for macromolecular crystallography applications. These scintillators show excellent absorption, optical, and mechanical properties.

  13. Macromolecular scaffolding: the relationship between nanoscale architecture and function in multichromophoric arrays for organic electronics.

    Science.gov (United States)

    Palermo, Vincenzo; Schwartz, Erik; Finlayson, Chris E; Liscio, Andrea; Otten, Matthijs B J; Trapani, Sara; Müllen, Klaus; Beljonne, David; Friend, Richard H; Nolte, Roeland J M; Rowan, Alan E; Samorì, Paolo

    2010-02-23

    The optimization of the electronic properties of molecular materials based on optically or electrically active organic building blocks requires a fine-tuning of their self-assembly properties at surfaces. Such a fine-tuning can be obtained on a scale up to 10 nm by mastering principles of supramolecular chemistry, i.e., by using suitably designed molecules interacting via pre-programmed noncovalent forces. The control and fine-tuning on a greater length scale is more difficult and challenging. This Research News highlights recent results we obtained on a new class of macromolecules that possess a very rigid backbone and side chains that point away from this backbone. Each side chain contains an organic semiconducting moiety, whose position and electronic interaction with neighboring moieties are dictated by the central macromolecular scaffold. A combined experimental and theoretical approach has made it possible to unravel the physical and chemical properties of this system across multiple length scales. The (opto)electronic properties of the new functional architectures have been explored by constructing prototypes of field-effect transistors and solar cells, thereby providing direct insight into the relationship between architecture and function.

  14. A technique for determining the deuterium/hydrogen contrast map in neutron macromolecular crystallography.

    Science.gov (United States)

    Chatake, Toshiyuki; Fujiwara, Satoru

    2016-01-01

    A difference in the neutron scattering length between hydrogen and deuterium leads to a high density contrast in neutron Fourier maps. In this study, a technique for determining the deuterium/hydrogen (D/H) contrast map in neutron macromolecular crystallography is developed and evaluated using ribonuclease A. The contrast map between the D2O-solvent and H2O-solvent crystals is calculated in real space, rather than in reciprocal space as performed in previous neutron D/H contrast crystallography. The present technique can thus utilize all of the amplitudes of the neutron structure factors for both D2O-solvent and H2O-solvent crystals. The neutron D/H contrast maps clearly demonstrate the powerful detectability of H/D exchange in proteins. In fact, alternative protonation states and alternative conformations of hydroxyl groups are observed at medium resolution (1.8 Å). Moreover, water molecules can be categorized into three types according to their tendency towards rotational disorder. These results directly indicate improvement in the neutron crystal structure analysis. This technique is suitable for incorporation into the standard structure-determination process used in neutron protein crystallography; consequently, more precise and efficient determination of the D-atom positions is possible using a combination of this D/H contrast technique and standard neutron structure-determination protocols.

  15. Dimethyl sulfoxide alterations of macromolecular synthesis by chick limb mesenchymal cells in vitro

    International Nuclear Information System (INIS)

    Major, F.W.; Parker, C.L.; Patterson, R.M.

    1986-01-01

    Earlier the authors reported that dimethyl sulfoxide (DMSO) inhibited the chondrogenesis of chick limb cells in vitro at concentrations of 30 mg/ml or greater. The present study was undertaken to determine if inhibition by DMSO might be due to an alteration in protein and/or DNA synthesis by the treated cells. Micromass cultures were prepared from stage 23-25 chick limb mesenchyme. The cells were treated with either 30 or 40 mg of DMSO/ml of culture medium for 24, 48, and 72 hr. After each treatment, protein and DNA synthesis were analyzed by the incorporation of [ 3 H]-leucine and [ 3 H]-thymidine, respectively. Cell cultures exposed to 40 mg DMSO/ml for 24 hr showed a significant decrease in protein synthesis, while there was no decrease in protein synthesis for cells treated with 30 mg DMSO/ml. At both 48 and 72 hr treatment with 30 mg of DMSO, there was a decrease in [ 3 H]-leucine incorporation. The thymidine studies indicated that there was a significant decrease in DNA synthesis as early as 24 hr for both DMSO concentrations. These findings suggest that the inhibition of chondrogenesis following DMSO treatment may be related to alterations in macromolecular synthesis possibly including extracellular cartilage matrix production

  16. Diffraction cartography: applying microbeams to macromolecular crystallography sample evaluation and data collection.

    Science.gov (United States)

    Bowler, Matthew W; Guijarro, Matias; Petitdemange, Sebastien; Baker, Isabel; Svensson, Olof; Burghammer, Manfred; Mueller-Dieckmann, Christoph; Gordon, Elspeth J; Flot, David; McSweeney, Sean M; Leonard, Gordon A

    2010-08-01

    Crystals of biological macromolecules often exhibit considerable inter-crystal and intra-crystal variation in diffraction quality. This requires the evaluation of many samples prior to data collection, a practice that is already widespread in macromolecular crystallography. As structural biologists move towards tackling ever more ambitious projects, new automated methods of sample evaluation will become crucial to the success of many projects, as will the availability of synchrotron-based facilities optimized for high-throughput evaluation of the diffraction characteristics of samples. Here, two examples of the types of advanced sample evaluation that will be required are presented: searching within a sample-containing loop for microcrystals using an X-ray beam of 5 microm diameter and selecting the most ordered regions of relatively large crystals using X-ray beams of 5-50 microm in diameter. A graphical user interface developed to assist with these screening methods is also presented. For the case in which the diffraction quality of a relatively large crystal is probed using a microbeam, the usefulness and implications of mapping diffraction-quality heterogeneity (diffraction cartography) are discussed. The implementation of these techniques in the context of planned upgrades to the ESRF's structural biology beamlines is also presented.

  17. Macromolecular crowding effects on reactions of TePixD (Tll0078).

    Science.gov (United States)

    Toyooka, Tsuguyoshi; Tanaka, Keisuke; Okajima, Koji; Ikeuchi, Masahiko; Tokutomi, Satoru; Terazima, Masahide

    2011-01-01

    To reveal macromolecular crowding effects on a chemical reaction of a BLUF (sensors of blue light using FAD) protein (PixD from a thermophilic cyanobacterium Thermosynechococcus elongatus BP-1 [TePixD, Tll0078]), the photoreaction was studied at various concentrations of the macromolecule Ficoll-70 by UV/Vis absorption spectroscopy and the pulsed laser-induced transient grating (TG) method. The absorption spectrum did not change with varying concentration of Ficoll-70. The crowding did not affect the quantum yield of the spectral red shift reaction, recovery rate of the product, rate constant of the volume change reaction and the magnitude of the volume change. However, the magnitude of the TG signal representing the diffusion-sensitive conformation change significantly increased on addition of Ficoll-70. This dependence was attributed to the crowding effect on the TePixD decamer-pentamer equilibrium in the solution. This result indicates that the TePixD reaction is more efficient in cellular than in in vitro conditions. © 2010 The Authors. Photochemistry and Photobiology © 2010 The American Society of Photobiology.

  18. Dimethyl sulfoxide alterations of macromolecular synthesis by chick limb mesenchymal cells in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Major, F.W.; Parker, C.L.; Patterson, R.M.

    1986-03-01

    Earlier the authors reported that dimethyl sulfoxide (DMSO) inhibited the chondrogenesis of chick limb cells in vitro at concentrations of 30 mg/ml or greater. The present study was undertaken to determine if inhibition by DMSO might be due to an alteration in protein and/or DNA synthesis by the treated cells. Micromass cultures were prepared from stage 23-25 chick limb mesenchyme. The cells were treated with either 30 or 40 mg of DMSO/ml of culture medium for 24, 48, and 72 hr. After each treatment, protein and DNA synthesis were analyzed by the incorporation of (/sup 3/H)-leucine and (/sup 3/H)-thymidine, respectively. Cell cultures exposed to 40 mg DMSO/ml for 24 hr showed a significant decrease in protein synthesis, while there was no decrease in protein synthesis for cells treated with 30 mg DMSO/ml. At both 48 and 72 hr treatment with 30 mg of DMSO, there was a decrease in (/sup 3/H)-leucine incorporation. The thymidine studies indicated that there was a significant decrease in DNA synthesis as early as 24 hr for both DMSO concentrations. These findings suggest that the inhibition of chondrogenesis following DMSO treatment may be related to alterations in macromolecular synthesis possibly including extracellular cartilage matrix production.

  19. Importance of Excluded Volume and Hydrodynamic Interactions on Macromolecular Diffusion in Vivo

    Science.gov (United States)

    Ando, Tadashi; Skolnick, Jeffrey

    2013-01-01

    The interiors of all living cells are highly crowded with macromolecules, which results in a considerable difference between the thermodynamics and kinetics of biological reactions in vivo from that in vitro. To begin to elucidate the principles of intermolecular dynamics in the crowded environment of cells, employing Brownian dynamics (BD) simulations, we examined possible mechanism(s) responsible for the great reduction in diffusion constants of macromolecules in vivo from that at infinite dilution. In an E. coli cytoplasm model comprised of 15 different macromolecule types at physiological concentrations, where macromolecules were represented by spheres with their Stokes radii, BD simulations were performed with and without hydrodynamic interactions (HI). Without HI, the calculated diffusion constant of green fluorescent protein (GFP) is much larger than experiment. On the other hand, when HI were considered, the in vivo experimental GFP diffusion constant is almost reproduced without adjustable parameters. In addition, HI give rise to significant, size independent intermolecular dynamic correlations. These results suggest that HI play an important role on macromolecular dynamics in vivo.

  20. Large area high-resolution CCD-based X-ray detector for macromolecular crystallography

    CERN Document Server

    Pokric, M; Jorden, A R; Cox, M P; Marshall, A; Long, P G; Moon, K; Jerram, P A; Pool, P; Nave, C; Derbyshire, G E; Helliwell, J R

    2002-01-01

    An X-ray detector system for macromolecular crystallography based on a large area charge-coupled device (CCD) sensor has been developed as part of a large research and development programme for advanced X-ray sensor technology, funded by industry and the Particle Physics and Astronomy Research Council (PPARC) in the UK. The prototype detector consists of two large area three-sides buttable charge-coupled devices (CCD 46-62 EEV), where the single CCD area is 55.3 mmx41.5 mm. Overall detector imaging area is easily extendable to 85 mmx110 mm. The detector consists of an optically coupled X-ray sensitive phosphor, skewed fibre-optic studs and CCDs. The crystallographic measurement requirements at synchrotron sources are met through a high spatial resolution (2048x1536 pixel array), high dynamic range (approx 10 sup 5), a fast readout (approx 1 s), low noise (<10e sup -) and much reduced parallax error. Additionally, the prototype detector system has been optimised by increasing its efficiency at low X-ray ene...

  1. Magnetic Control of Macromolecular Conformations in Supramolecular Anionic Polysaccharide-Iron Complexes.

    Science.gov (United States)

    Schefer, Larissa; Bulant, Ariane; Zeder, Christophe; Saha, Abhijit; Mezzenga, Raffaele

    2015-11-02

    The anionic iota carrageenan polysaccharide is enriched with Fe(II) and Fe(III) by ion exchange against FeSO4 and FeCl3 . With divalent iron, portions of polymer chains undergo a secondary structure transition from random coils to single helices. The single-chain macromolecular conformations can be manipulated by an external magnetic field: upon exposure to 1.1 T, the helical portions exhibit 1.5-fold stiffening and 1.1-fold stretching, whereas the coil conformations respond much less as a result of lower contents of condensed iron ions. Along with the coil-helix transition, the trivalent iron triggers the formation of superstructures. The applicability of iron-enriched iota carrageenan as functional ingredient for food fortification is tested by free Fe(2+) and Fe(3+) contents, respectively, with the most promising iota-Fe(III) yielding 53% of bound iron, which is due to the superstructures, where the ferric ions are chelated by the supramolecularly self-assembled polymer host. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Macromolecular basis for homocystein-induced changes in proteoglycan structure in growth and arteriosclerosis.

    Science.gov (United States)

    McCully, K S

    1972-01-01

    Cell culture monolayers deficient in cystathionine synthetase bound more inorganic sulfate than normal cell monolayers during growth to confluence; this was correlated with the production of granular proteoglycan by the abnormal cells and fibrillar proteoglycan by normal cells. Homocysteine was demonstrated to be an active precursor of esterified sulfate, confirming our previous finding of this sulfation pathway in liver. The cell cultures deficient in cystathionine synthetase were found to assume an abnormal cellular distribution on the surface of the culture dish, resembling the distribution assumed by neoplastic cells with loss of contact inhibition; the degree of abnormality of the cellular distribution was correlated with the amount of granular proteoglycan produced by the cells and the amount of inorganic sulfate binding by the cell monolayers. Pyridoxine was found to increase the growth rate of cell cultures from a patient with pyridoxineresponsive homocystinuria and to increase the production of fibrillar proteoglycan by the cells; no effect of pyridoxine was observed in the cell cultures from a patient who failed to respond to pyridoxine therapy. The findings suggest that the change in macromolecular conformation of cellular proteoglycans from fibrillar to granular is due to increased sulfation of the carbohydrate envelope of the molecule. The significance of the findings is related to the pathogenesis of homocystinuria, the phenomenon of contact inhibition, the action of growth hormone and initiation of arteriosclerotic plaques.

  3. Rapid automated superposition of shapes and macromolecular models using spherical harmonics.

    Science.gov (United States)

    Konarev, Petr V; Petoukhov, Maxim V; Svergun, Dmitri I

    2016-06-01

    A rapid algorithm to superimpose macromolecular models in Fourier space is proposed and implemented ( SUPALM ). The method uses a normalized integrated cross-term of the scattering amplitudes as a proximity measure between two three-dimensional objects. The reciprocal-space algorithm allows for direct matching of heterogeneous objects including high- and low-resolution models represented by atomic coordinates, beads or dummy residue chains as well as electron microscopy density maps and inhomogeneous multi-phase models ( e.g. of protein-nucleic acid complexes). Using spherical harmonics for the computation of the amplitudes, the method is up to an order of magnitude faster than the real-space algorithm implemented in SUPCOMB by Kozin & Svergun [ J. Appl. Cryst. (2001 ▸), 34 , 33-41]. The utility of the new method is demonstrated in a number of test cases and compared with the results of SUPCOMB . The spherical harmonics algorithm is best suited for low-resolution shape models, e.g . those provided by solution scattering experiments, but also facilitates a rapid cross-validation against structural models obtained by other methods.

  4. Photochemical internalisation of a macromolecular protein toxin using a cell penetrating peptide-photosensitiser conjugate.

    Science.gov (United States)

    Wang, Julie T-W; Giuntini, Francesca; Eggleston, Ian M; Bown, Stephen G; MacRobert, Alexander J

    2012-01-30

    Photochemical internalisation (PCI) is a site-specific technique for improving cellular delivery of macromolecular drugs. In this study, a cell penetrating peptide, containing the core HIV-1 Tat 48-57 sequence, conjugated with a porphyrin photosensitiser has been shown to be effective for PCI. Herein we report an investigation of the photophysical and photobiological properties of a water soluble bioconjugate of the cationic Tat peptide with a hydrophobic tetraphenylporphyrin derivative. The cellular uptake and localisation of the amphiphilic bioconjugate was examined in the HN5 human head and neck squamous cell carcinoma cell line. Efficient cellular uptake and localisation in endo/lysosomal vesicles was found using fluorescence detection, and light-induced, rupture of the vesicles resulting in a more diffuse intracellular fluorescence distribution was observed. Conjugation of the Tat sequence with a hydrophobic porphyrin thus enables cellular delivery of an amphiphilic photosensitiser which can then localise in endo/lysosomal membranes, as required for effective PCI treatment. PCI efficacy was tested in combination with a protein toxin, saporin, and a significant reduction in cell viability was measured versus saporin or photosensitiser treatment alone. This study demonstrates that the cell penetrating peptide-photosensitiser bioconjugation strategy is a promising and versatile approach for enhancing the therapeutic potential of bioactive agents through photochemical internalisation. Copyright © 2011 Elsevier B.V. All rights reserved.

  5. The Effect of Attractive Interactions and Macromolecular Crowding on Crystallins Association.

    Directory of Open Access Journals (Sweden)

    Jiachen Wei

    Full Text Available In living systems proteins are typically found in crowded environments where their effective interactions strongly depend on the surrounding medium. Yet, their association and dissociation needs to be robustly controlled in order to enable biological function. Uncontrolled protein aggregation often causes disease. For instance, cataract is caused by the clustering of lens proteins, i.e., crystallins, resulting in enhanced light scattering and impaired vision or blindness. To investigate the molecular origins of cataract formation and to design efficient treatments, a better understanding of crystallin association in macromolecular crowded environment is needed. Here we present a theoretical study of simple coarse grained colloidal models to characterize the general features of how the association equilibrium of proteins depends on the magnitude of intermolecular attraction. By comparing the analytic results to the available experimental data on the osmotic pressure in crystallin solutions, we identify the effective parameters regimes applicable to crystallins. Moreover, the combination of two models allows us to predict that the number of binding sites on crystallin is small, i.e. one to three per protein, which is different from previous estimates. We further observe that the crowding factor is sensitive to the size asymmetry between the reactants and crowding agents, the shape of the protein clusters, and to small variations of intermolecular attraction. Our work may provide general guidelines on how to steer the protein interactions in order to control their association.

  6. Macromolecular crystallographic results obtained at CHESS using a detector incorporating a charge-coupled device

    International Nuclear Information System (INIS)

    Thiel, D.J.; Walter, R.L.; Ealick, S.E.; Bilderback, D.H.; Tate, M.W.; Gruner, S.M.; Eikenberry, E.F.

    1995-01-01

    Results from various macromolecular crystallography experiments are presented showing the effectiveness of a recently installed detector incorporating a charge-coupled device (CCD). This detector uses a 1024x1024 CCD directly coupled to an x-ray sensitive phosphor by a fiber optic taper. The pixel size at the phosphor (50 μm) results in a point spread of 80 μm full width at half-maximum. Even with the relatively small active area, 51x51 mm 2 , about 150 orders of diffraction can be resolved across the detector face. With this detector format, well-resolved diffraction data have been collected from unit cells with edges as large as 360 A. In an offset configuration, the detector has been used to collect extremely high-resolution data (1 A). A number of data sets have been collected having R sym values in the 4%--6% range; in the case of room-temperature lysozyme, an R sym value as small as 2.1 was obtained for a 2.5 A resolution data set. In addition to fixed wavelength studies, the detector has also been used to collect MAD data. In all cases, the use of this detector has proven to be more efficient than using standard image plates since less x-ray exposure time and no distinct scanning step are required. Furthermore, the data quality is as good and in some cases better than those from previous image plate measurements

  7. The structural biology center at the APS: an integrated user facility for macromolecular crystallography

    International Nuclear Information System (INIS)

    Rosenbaum, G.; Westbrook, E.M.

    1997-01-01

    The Structural Biology Center (SBC) has developed and operates a sector (undulator and bending magnet) of the APS as a user facility for macromolecular crystallography. Crystallographically determined structures of proteins, nucleic acids and their complexes with proteins, viruses, and complexes between macromolecules and small ligands have become of central importance in molecular and cellular biology. Major design goals were to make the extremely high brilliance of the APS available for brilliance limited studies, and to achieve a high throughput of less demanding studies, as well as optimization for MAS-phasing. Crystal samples will include extremely small crystals, crystals with large unit cells (viruses, ribosomes, etc.) and ensembles of closely similar crystal structures for drug design, protein engineering, etc. Data are recorded on a 3000x3000 pixel CCD-area detector (optionally on image plates). The x-ray optics of both beamlines has been designed to produce a highly demagnified image of the source in order to match the focal size with the sizes of the sample and the resolution element of the detector. Vertical focusing is achieved by a flat, cylindrically bent mirror. Horizontal focusing is achieved by sagitally bending the second crystal of the double crystal monochromator. Monochromatic fluxes of 1.3 * 10 13 ph/s into focal sizes of 0.08 mm (horizontal)x0.04 mm (vertical) FWHM (flux density 3.5 * 10 15 ph/s/mm 2 ) have been recorded.copyright 1997 American Institute of Physics

  8. Synthesis and Self-Assembly of Amphiphilic Triblock Terpolymers with Complex Macromolecular Architecture

    KAUST Repository

    Polymeropoulos, George

    2015-11-25

    Two star triblock terpolymers (PS-b-P2VP-b-PEO)3 and one dendritic-like terpolymer [PS-b-P2VP-b-(PEO)2]3 of PS (polystyrene), P2VP (poly(2-vinylpyridine)), and PEO (poly(ethylene oxide)), never reported before, were synthesized by combining atom transfer radical and anionic polymerizations. The synthesis involves the transformation of the -Br groups of the previously reported Br-terminated 3-arm star diblock copolymers to one or two -OH groups, followed by anionic polymerization of ethylene oxide to afford the star or dendritic structure, respectively. The well-defined structure of the terpolymers was confirmed by static light scattering, size exclusion chromatography, and NMR spectroscopy. The self-assembly in solution and the morphology in bulk of the terpolymers, studied by dynamic light scattering and transmission electron microscopy, respectively, reveal new insights in the phase separation of these materials with complex macromolecular architecture. © 2015 American Chemical Society.

  9. RoboDiff: combining a sample changer and goniometer for highly automated macromolecular crystallography experiments.

    Science.gov (United States)

    Nurizzo, Didier; Bowler, Matthew W; Caserotto, Hugo; Dobias, Fabien; Giraud, Thierry; Surr, John; Guichard, Nicolas; Papp, Gergely; Guijarro, Matias; Mueller-Dieckmann, Christoph; Flot, David; McSweeney, Sean; Cipriani, Florent; Theveneau, Pascal; Leonard, Gordon A

    2016-08-01

    Automation of the mounting of cryocooled samples is now a feature of the majority of beamlines dedicated to macromolecular crystallography (MX). Robotic sample changers have been developed over many years, with the latest designs increasing capacity, reliability and speed. Here, the development of a new sample changer deployed at the ESRF beamline MASSIF-1 (ID30A-1), based on an industrial six-axis robot, is described. The device, named RoboDiff, includes a high-capacity dewar, acts as both a sample changer and a high-accuracy goniometer, and has been designed for completely unattended sample mounting and diffraction data collection. This aim has been achieved using a high level of diagnostics at all steps of the process from mounting and characterization to data collection. The RoboDiff has been in service on the fully automated endstation MASSIF-1 at the ESRF since September 2014 and, at the time of writing, has processed more than 20 000 samples completely automatically.

  10. C,N-2-[(Dimethylamino)methyl]phenylplatinum Complexes Functionalized with C60 as Macromolecular Building Blocks

    NARCIS (Netherlands)

    Koten, G. van; Meijer, M.D.; Wolf, E. de; Lutz, M.H.; Spek, A.L.; Klink, G.P.M. van

    2001-01-01

    The application of platinum(II) complexes based on the N,N-dimethylbenzylamine ligand (abbreviated as H-C,N) in macromolecular synthesis was demonstrated. Two cationic C,N-platinum moieties were linked with a 4,4'-bipyridine bridge, giving [{C6H4(CH2NMe2)-2-Pt(PPh3)}2(4,4'-bpy)](BF4)2 (2), the

  11. Macromolecular pHPMA-based nanoparticles with cholesterol for solid tumor targeting: behavior in HSA protein environment

    Czech Academy of Sciences Publication Activity Database

    Zhang, X.; Niebuur, B.-J.; Chytil, Petr; Etrych, Tomáš; Filippov, Sergey K.; Kikhney, A.; Wieland, D. C. F.; Svergun, D. I.; Papadakis, C. M.

    2018-01-01

    Roč. 19, č. 2 (2018), s. 470-480 ISSN 1525-7797 R&D Projects: GA ČR(CZ) GC15-10527J; GA MZd(CZ) NV16-28594A; GA MŠk(CZ) LO1507 Institutional support: RVO:61389013 Keywords : polymer carriers * N-(2-hydroxypropyl)methacrylamide * tumor targeting Subject RIV: CD - Macromolecular Chemistry OBOR OECD: Polymer science Impact factor: 5.246, year: 2016

  12. 08B1-1: an automated beamline for macromolecular crystallography experiments at the Canadian Light Source.

    Science.gov (United States)

    Fodje, Michel; Grochulski, Pawel; Janzen, Kathryn; Labiuk, Shaunivan; Gorin, James; Berg, Russ

    2014-05-01

    Beamline 08B1-1 is a recently commissioned bending-magnet beamline at the Canadian Light Source. The beamline is designed for automation and remote access. Together with the undulator-based beamline 08ID-1, they constitute the Canadian Macromolecular Crystallography Facility. This paper describes the design, specifications, hardware and software of beamline 08B1-1. A few scientific results using data obtained at the beamline will be highlighted.

  13. A facile metal-free "grafting-from" route from acrylamide-based substrate toward complex macromolecular combs

    KAUST Repository

    Zhao, Junpeng

    2013-01-01

    High-molecular-weight poly(N,N-dimethylacrylamide-co-acrylamide) was used as a model functional substrate to investigate phosphazene base (t-BuP 4)-promoted metal-free anionic graft polymerization utilizing primary amide moieties as initiating sites. The (co)polymerization of epoxides was proven to be effective, leading to macromolecular combs with side chains being single- or double-graft homopolymer, block copolymer and statistical copolymer. © 2013 The Royal Society of Chemistry.

  14. Organic sulphur in macromolecular sedimentary organic matter : I. Structure and origin of sulphur-containing moieties in kerogen, asphaltene and coal as revealed by flash pyrolysis

    NARCIS (Netherlands)

    Sinninghe Damsté, J.S.; Eglinton, T.I.; Leeuw, J.W. de; Schenk, P.A.

    1989-01-01

    The distributions of sulphur-containing compounds generated by flash pyrolysis of macromolecular sedimentary organic matter (kerogen, coal, asphaltenes) were studied by gas chromatography in combination with S-selective flame photometric detection or mass spectrometry. The abundance of

  15. Macromolecular crowding enhances the binding of superoxide dismutase to xanthine oxidase: implications for protein-protein interactions in intracellular environments.

    Science.gov (United States)

    Zhou, Yu-Ling; Liao, Jun-Ming; Chen, Jie; Liang, Yi

    2006-01-01

    Physiological medium constitutes a crowded environment that serves as the field of action for protein-protein interaction in vivo. Measuring protein-protein interaction in crowded solutions can mimic this environment. Here we report the application of fluorescence spectroscopy and resonant mirror biosensor to investigate the interactions of bovine milk xanthine oxidase and bovine erythrocyte copper, zinc-superoxide dismutase in crowded solutions. Four nonspecific high molecular mass crowding agents, poly(ethylene glycol) 2000 and 20,000, Ficoll 70, and dextran 70, and one low molecular mass compound, glycerol, are used. Superoxide dismutase shows a strong and macromolecular crowding agent concentration-dependent binding affinity to xanthine oxidase. Addition of high concentrations of such high molecular mass crowding agents increases the binding constant remarkably and thus stabilizes superoxide dismutase activity, compared to those in the absence of crowding agents. In contrast, glycerol has little effect on the binding constant and decreases superoxide dismutase activity over the same concentration range. Such a pattern suggests that the enhancing effects of polymers and polysaccharides on the binding are due to macromolecular crowding. Taken together, these results indicate that macromolecular crowding enhances the binding of superoxide dismutase to xanthine oxidase and is favorable to the function of superoxide dismutase.

  16. Macromolecular composition and drug-loading effect on the delivery of paclitaxel and folic acid from acrylic matrices.

    Science.gov (United States)

    Gagliardi, M; Silvestri, D; Cristallini, C

    2010-08-01

    Drug delivery systems based on synthetic polymers are widely employed in the treatment of several pathologies. In particular, the use of implantable devices able to release one or more active principles in a topic site with a controlled delivery kinetic represents an important improvement in this field. However, the release kinetic, that could be affected by different parameters, like polymer composition or chemical nature and initial drug loading, represents one of the problems related to the implantation of delivery systems. In this study, acrylic membranes with different macromolecular composition were prepared and studied analyzing delivery kinetic properties. Drug delivery systems were prepared using as matrix the copolymer poly(methylmethacrylate-co-butylmethacrylate) in three different compositions and folic acid (less hydrophobic) or Paclitaxel (more hydrophobic) as drugs, to evaluate the effect of macromolecular composition and hydrophilicity degree on the release properties. In addition, the effect of the initial drug loading was considered, loading drug delivery systems with four different initial drug percentages. Results showed a direct dependence of kinetics from macromolecular composition, hydrophilicity degree of solutes, and initial drug loading, allowing one to conclude that it is possible to design and to develop drug delivery systems starting from poly(methylmethacrylate-co-butylmethacrylate) matrices with specific properties by varying these three parameters.

  17. Spontaneous Metacognition in Rhesus Monkeys.

    Science.gov (United States)

    Rosati, Alexandra G; Santos, Laurie R

    2016-09-01

    Metacognition is the ability to think about thinking. Although monitoring and controlling one's knowledge is a key feature of human cognition, its evolutionary origins are debated. In the current study, we examined whether rhesus monkeys (Macaca mulatta; N = 120) could make metacognitive inferences in a one-shot decision. Each monkey experienced one of four conditions, observing a human appearing to hide a food reward in an apparatus consisting of either one or two tubes. The monkeys tended to search the correct location when they observed this baiting event, but engaged in information seeking-by peering into a center location where they could check both potential hiding spots-if their view had been occluded and information seeking was possible. The monkeys only occasionally approached the center when information seeking was not possible. These results show that monkeys spontaneously use information about their own knowledge states to solve naturalistic foraging problems, and thus provide the first evidence that nonhumans exhibit information-seeking responses in situations with which they have no prior experience. © The Author(s) 2016.

  18. Spontaneous flocking in human groups.

    Science.gov (United States)

    Belz, Michael; Pyritz, Lennart W; Boos, Margarete

    2013-01-01

    Flocking behaviour, as a type of self-organised collective behaviour, is described as the spatial formation of groups without global control and explicit inter-individual recruitment signals. It can be observed in many animals, such as bird flocks, shoals or herds of ungulates. Spatial attraction between humans as the central component of flocking behaviour has been simulated in a number of seminal models but it has not been detected experimentally in human groups so far. The two other sub-processes of this self-organised collective movement - collision avoidance and alignment - are excluded or held constant respectively in this study. We created a computer-based, multi-agent game where human players, represented as black dots, moved on a virtual playground. The participants were deprived of social cues about each other and could neither communicate verbally nor nonverbally. They played two games: (1) Single Game, where other players were invisible, and (2) Joint Game, where each player could see players' positions in a local radius around himself/herself. We found that individuals approached their neighbours spontaneously if their positions were visible, leading to less spatial dispersion of the whole group compared to moving alone. We conclude that human groups show the basic component of flocking behaviour without being explicitly instructed or rewarded to do so. Copyright © 2012 Elsevier B.V. All rights reserved.

  19. Simultaneous bilateral primary spontaneous pneumothorax

    Directory of Open Access Journals (Sweden)

    Arife Zeybek

    2014-04-01

    Full Text Available Simultaneous bilateral primary pneumothorax is a very rare (1.6 / 100,000 and life-threatening condition. Clinical presentation may vary from mild dyspnea to tension pneumothorax. It may be milder particularly in younger patients, but more severe in patients with advanced age, and tube thoracostomy is a life preserver in the latter group. Since mortality and recurrence rates following tube thoracostomy are high, endoscopic approaches to bilateral hemithorax have been reported in literature. Apical wedge resection and pleural procedures are recommended in video thoracoscopy or mini thoracotomy even if no bulla and/or bleb are detected. Bilateral surgical interventions and additional pleural procedures are associated with increased rate of post-operative complications and longer postoperative hospital-stays. As a first-line approach, the surgical method toward any side of lung with air leakage following a previous tube thoracostomy is considered less invasive, especially in younger patients. Here, we present a case of simultaneous bilateral primary spontaneous pneumothorax (SBPSP in a 21-year old male with no history of smoking and chronic pulmonary disease. A unilateral surgical intervention was performed, and no recurrence was observed during 5-year follow up.

  20. Bilateral spontaneous hemotympanum: Case report

    Directory of Open Access Journals (Sweden)

    Economou Nicolas C

    2006-10-01

    Full Text Available Abstract Background The most common causes of hemotympanum are therapeutic nasal packing, epistaxis, blood disorders and blunt trauma to the head. Hemotympanum is characterized as idiopathic, when it is detected in the presence of chronic otitis media. A rare case of spontaneous bilateral hemotympanum in a patient treated with anticoagulants is presented herein. Case presentation A 72-year-old male presented with acute deterioration of hearing. In the patient's medical history aortic valve replacement 1 year before presentation was reported. Since then he had been administered regularly coumarinic anticoagulants, with INR levels maintained between 3.4 and 4.0. Otoscopy revealed the presence of bilateral hemotympanum. The audiogram showed symmetrical moderately severe mixed hearing loss bilaterally, with the conductive component predominating. Tympanograms were flat bilaterally with absent acoustic reflexes. A computerized tomography scan showed the presence of fluid in the mastoid and middle ear bilaterally. Treatment was conservative and consisted of a 10-day course of antibiotics, anticongestants and temporary interruption of the anticoagulant therapy. After 3 weeks, normal tympanic membranes were found and hearing had returned to previous levels. Conclusion Anticoagulant intake should be included in the differential diagnosis of hemotympanum, because its detection and appropriate treatment may lead to resolution of the disorder.

  1. Clock frequency estimation under spontaneous emission

    Science.gov (United States)

    Qin, Xi-Zhou; Huang, Jia-Hao; Zhong, Hong-Hua; Lee, Chaohong

    2018-02-01

    We investigate the quantum dynamics of a driven two-level system under spontaneous emission and its application in clock frequency estimation. By using the Lindblad equation to describe the system, we analytically obtain its exact solutions, which show three different regimes: Rabi oscillation, damped oscillation, and overdamped decay. From the analytical solutions, we explore how the spontaneous emission affects the clock frequency estimation. We find that under a moderate spontaneous emission rate, the transition frequency can still be inferred from the Rabi oscillation. Our results enable potential practical applications in frequency measurement and quantum control under decoherence.

  2. Spontaneous Bacterial Peritonitis in Subclinical Hypothyroidism

    Directory of Open Access Journals (Sweden)

    Dalip Gupta

    2013-11-01

    Full Text Available Hypothyroidism is an uncommon cause of ascites. Here we describe a case of a 75 year-old female patient with spontaneous bacterial peritonitis and subclinical hypothyroidism that resolved with thyroid replacement and antibiotic therapy respectively. Ascitic fluid analysis revealed a gram-positive bacterium on gram staining. A review of the literature revealed just one other reported case of myxoedema ascites with concomitant spontaneous bacterial peritonitis and no case has till been reported of spontaneous bacterial peritonitis in subclinical hypothyroidism.

  3. Spontaneous regression of an invasive thymoma.

    Science.gov (United States)

    Yutaka, Yojiro; Omasa, Mitsugu; Shikuma, Kei; Okuda, Masato; Taki, Toshihiko

    2009-05-01

    Although there are many reports of spontaneous regression of noninvasive thymoma, there are no reports of spontaneous regression of an invasive thymoma. Moreover, the mechanism of the spontaneous regression is still unknown. The present case concerns a 47-year-old man who presented with chest pain. Computed tomography (CT) showed a large anterior mediastinal mass with left pleural effusion that occluded the innominate vein. The tissue obtained by video-assisted thoracic surgery suggested a diagnosis of invasive thymic carcinoma. One month later CT showed prominent regression of the tumor, and the tumor was completely resected. On pathology, the diagnosis was thymoma type B3.

  4. Spontaneous Dissection of the Superior Mesenteric Artery

    International Nuclear Information System (INIS)

    Sheldon, Patrick J.; Esther, James B.; Sheldon, Elana L.; Sparks, Steven R.; Brophy, David P.; Oglevie, Steven B.

    2001-01-01

    Spontaneous dissection of the superior mesenteric artery (SMA) is a rare occurrence, especially when not associated with aortic dissection. Currently, only 28 cases appear to have been reported. Due to the scarcity of cases in the literature, the natural history of isolated, spontaneous SMA dissection is unclear. CT has been reported to be useful for the initial diagnosis of SMA dissection [2-5]. We present two recent cases of spontaneous SMA dissection in which enhanced spiral CT was instrumental in following the disease process and guiding clinical decision making

  5. Does Spontaneous Favorability to Power (vs. Universalism) Values Predict Spontaneous Prejudice and Discrimination?

    Science.gov (United States)

    Souchon, Nicolas; Maio, Gregory R; Hanel, Paul H P; Bardin, Brigitte

    2017-10-01

    We conducted five studies testing whether an implicit measure of favorability toward power over universalism values predicts spontaneous prejudice and discrimination. Studies 1 (N = 192) and 2 (N = 86) examined correlations between spontaneous favorability toward power (vs. universalism) values, achievement (vs. benevolence) values, and a spontaneous measure of prejudice toward ethnic minorities. Study 3 (N = 159) tested whether conditioning participants to associate power values with positive adjectives and universalism values with negative adjectives (or inversely) affects spontaneous prejudice. Study 4 (N = 95) tested whether decision bias toward female handball players could be predicted by spontaneous attitude toward power (vs. universalism) values. Study 5 (N = 123) examined correlations between spontaneous attitude toward power (vs. universalism) values, spontaneous importance toward power (vs. universalism) values, and spontaneous prejudice toward Black African people. Spontaneous positivity toward power (vs. universalism) values was associated with spontaneous negativity toward minorities and predicted gender bias in a decision task, whereas the explicit measures did not. These results indicate that the implicit assessment of evaluative responses attached to human values helps to model value-attitude-behavior relations. © 2016 The Authors. Journal of Personality Published by Wiley Periodicals, Inc.

  6. Photochemical internalization of therapeutic macromolecular agents: a novel strategy to kill multidrug-resistant cancer cells.

    Science.gov (United States)

    Selbo, Pål K; Weyergang, Anette; Bonsted, Anette; Bown, Stephen G; Berg, Kristian

    2006-11-01

    Drug resistance is a major problem for chemotherapy. Entrapment of anticancer drugs in endolysosomal compartments or active extrusions by plasma membrane proteins of the ATP-binding cassette (ABC) superfamily are important resistance mechanisms. This study evaluated photochemical internalization (PCI) of membrane-impermeable macromolecules that are not the target of ABC drug pumps for treating multidrug-resistant (MDR) cancer cells. We used the drug-sensitive uterine fibrosarcoma cell line MES-SA and its MDR, P-glycoprotein (P-gp)-overexpressing derivative MES-SA/Dx5 with the photosensitizer disulfonated meso-tetraphenylporphine (TPPS(2a)) and broad spectrum illumination. The PCI of doxorubicin, the ribosome-inactivating protein gelonin and adenoviral transduction were assessed in both cell lines, together with the uptake and excretion of TPPS(2a) and of two fluid phase markers easily detectable by fluorescence [lucifer yellow (LY) and fluorescein isothiocyanate (FITC)-dextran], as a model of gelonin uptake. Both cell lines were resistant to PCI of doxorubicin, but equally sensitive to PCI of gelonin, even though the endocytosis rates of LY and FITC-dextran were significantly lower in the MDR cells. In control studies, MES-SA/Dx5 cells were more resistant to photodynamic therapy (TPPS(2a) + light only). This was not mediated by P-gp, as there were no differences in the uptake and efflux of TPPS(2a) between the cell lines. After adenoviral infection, PCI enhanced gene delivery in both cell lines. In conclusion, PCI of macromolecular therapeutic agents that are not targets of P-gp is a novel therapeutic strategy to kill MDR cancer cells.

  7. Methods for synthesizing the macromolecular constituents of smart nanosized carriers for controlled drug delivery.

    Science.gov (United States)

    Balaure, Paul Catalin; Grumezescu, Alexandru Mihai

    2014-01-01

    Smart multifunctional polymeric nanocarriers able to respond to physicochemical changes in their environment or to external stimuli represent a new paradigm in the field of pharmaceutical formulations for controlled drug delivery. The introductory part of the present review deals with this new concept and presents the main advantages resulting from the use of such nanovehicles instead of conventional, much larger drug delivery systems. The access to drug nanocarriers based on smart supramolecular polymeric materials is primarily limited by the available polymerization methods capable to produce polymers with low polydispersity index, as well as much more complex macromolecular architectures with strictly controlled chemical composition, such as block copolymers and star or graft polymers or copolymers. This article reviews the state-of-the art in controlled/"living" free radical polymerization techniques as well as ring opening polymerization methods. Nitroxide mediated free radical polymerization (NMP), atom transfer radical polymerization (ATRP), reversible addition-fragmentation chain-transfer polymerization (RAFT), single electron transfer-living radical polymerization (SET-LRP), single electron transfer-nitroxide radical coupling reaction (SET-NRC), cationic ring opening polymerization (CROP), anionic ring opening polymerization (AROP), and metal catalyzed ring opening polymerization are described, highlighting their mechanistic details and their synthetic potential as well as their limitations. The final part of the article is dedicated to a special type of unimolecular, monodisperse nanocarriers - the dendrimers. Both divergent and convergent approaches to dendrimer synthesis are described along with the therapeutic applications taking advantage of the unique branched tree-like globular structure of dendrimers to treat cancer.

  8. Phase behaviour of macromolecular liquid crystalline materials. Computational studies at the molecular level

    International Nuclear Information System (INIS)

    Stimson, Lorna M.

    2003-01-01

    Molecular simulations provide an increasingly useful insight into the static and dynamic characteristics of materials. In this thesis molecular simulations of macro-molecular liquid crystalline materials are reported. The first liquid crystalline material that has been investigated is a side chain liquid crystal polymer (SCLCP). In this study semi-atomistic molecular dynamics simulations have been conducted at a range of temperatures and an aligning potential has been applied to mimic the effect of a magnetic field. In cooling the SCLCP from an isotropic melt, microphase separation was observed yielding a domain structure. The application of a magnetic field to this structure aligns the domains producing a stable smectic mesophase. This is the first study in which mesophases have been observed using an off-lattice model of a SCLCP. The second material that has been investigated is a dendrimer with terminal mesogenic functionalization. Here, a multi-scale approach has been taken with Monte Carlo studies of a single dendrimer molecule in the gas phase at the atomistic level, semi-atomistic molecular dynamics of a single molecule in liquid crystalline solvents and a coarse-grained molecular dynamics study of the dendrimer in the bulk. The coarse-grained model has been developed and parameterized using the results of the atomistic and semi-atomistic work. The single molecule studies showed that the liquid crystalline dendrimer was able to change its structure by conformational changes in the flexible chains that link the mesogenic groups to the core. Structural change was seen under the application of a mean field ordering potential in the gas phase, and in the presence of liquid crystalline solvents. No liquid crystalline phases were observed for the bulk phase studies of the coarse-grained model. However, when the length of the mesogenic units was increased there was some evidence for microphase separation in these systems. (author)

  9. Facilities for macromolecular crystallography at the Helmholtz-Zentrum Berlin

    Science.gov (United States)

    Mueller, Uwe; Darowski, Nora; Fuchs, Martin R.; Förster, Ronald; Hellmig, Michael; Paithankar, Karthik S.; Pühringer, Sandra; Steffien, Michael; Zocher, Georg; Weiss, Manfred S.

    2012-01-01

    Three macromolecular crystallography (MX) beamlines at the Helmholtz-Zentrum Berlin (HZB) are available for the regional, national and international structural biology user community. The state-of-the-art synchrotron beamlines for MX BL14.1, BL14.2 and BL14.3 are located within the low-β section of the BESSY II electron storage ring. All beamlines are fed from a superconducting 7 T wavelength-shifter insertion device. BL14.1 and BL14.2 are energy tunable in the range 5–16 keV, while BL14.3 is a fixed-energy side station operated at 13.8 keV. All three beamlines are equipped with CCD detectors. BL14.1 and BL14.2 are in regular user operation providing about 200 beam days per year and about 600 user shifts to approximately 50 research groups across Europe. BL14.3 has initially been used as a test facility and was brought into regular user mode operation during the year 2010. BL14.1 has recently been upgraded with a microdiffractometer including a mini-κ goniometer and an automated sample changer. Additional user facilities include office space adjacent to the beamlines, a sample preparation laboratory, a biology laboratory (safety level 1) and high-end computing resources. In this article the instrumentation of the beamlines is described, and a summary of the experimental possibilities of the beamlines and the provided ancillary equipment for the user community is given. PMID:22514183

  10. Macromolecular organization of human centromeric regions reveals high-frequency, polymorphic macro DNA repeats.

    Science.gov (United States)

    Jabs, E W; Goble, C A; Cutting, G R

    1989-01-01

    To analyze the macromolecular organization of human centromeric regions, we used alpha-satellite, or alphoid, repetitive DNA sequences specific to the centromeres of human chromosomes 6 (D6Z1), X (XC), and Y (YC-2) and the technique of pulsed-field gel electrophoresis. Genomic DNA from 24 normal, unrelated individuals was digested and separated into fragments ranging from 23 kilobases (kb) to 2 megabases (Mb) in length. Digestion with 12 different restriction enzymes with 4- to 8-base-pair recognition sequences and hybridization with alphoid sequences revealed chromosome-specific hybridization patterns. Similarities in the organization of the centromeric regions of the three chromosomes included NotI, SfiI, and SalI fragments of greater than 2 Mb and Sau3A1 and Alu I fragments of less than 150 kb. Each restriction enzyme with a 6-base-pair recognition sequence (Ava II, BamHI, HindIII, Hpa I, Pst I, Sal I, Sst I, and Xba I) detected polymorphic DNA fragments of 50 kb to 2 Mb. Forty percent or more of the individuals screened revealed a unique hybridization pattern with these enzymes and at least one of the three chromosome-specific alphoid probes. Five individuals differed from one another in hybridization pattern for each of the three enzymes HindIII, HpaI, and SstI and for each of the three centromeric probes. All 24 individuals could be distinguished on the basis of unique hybridization patterns with only two enzymes and one chromosome-specific alphoid probe. Family studies showed that these polymorphisms are inherited. The high frequency of these macro restriction fragment length polymorphisms illustrates the high degree of variability of the centromeric region among normal individuals and demonstrates its usefulness for DNA fingerprinting and pericentromeric mapping by linkage analysis.

  11. The use of workflows in the design and implementation of complex experiments in macromolecular crystallography

    International Nuclear Information System (INIS)

    Brockhauser, Sandor; Svensson, Olof; Bowler, Matthew W.; Nanao, Max; Gordon, Elspeth; Leal, Ricardo M. F.; Popov, Alexander; Gerring, Matthew; McCarthy, Andrew A.; Gotz, Andy

    2012-01-01

    A powerful and easy-to-use workflow environment has been developed at the ESRF for combining experiment control with online data analysis on synchrotron beamlines. This tool provides the possibility of automating complex experiments without the need for expertise in instrumentation control and programming, but rather by accessing defined beamline services. The automation of beam delivery, sample handling and data analysis, together with increasing photon flux, diminishing focal spot size and the appearance of fast-readout detectors on synchrotron beamlines, have changed the way that many macromolecular crystallography experiments are planned and executed. Screening for the best diffracting crystal, or even the best diffracting part of a selected crystal, has been enabled by the development of microfocus beams, precise goniometers and fast-readout detectors that all require rapid feedback from the initial processing of images in order to be effective. All of these advances require the coupling of data feedback to the experimental control system and depend on immediate online data-analysis results during the experiment. To facilitate this, a Data Analysis WorkBench (DAWB) for the flexible creation of complex automated protocols has been developed. Here, example workflows designed and implemented using DAWB are presented for enhanced multi-step crystal characterizations, experiments involving crystal reorientation with kappa goniometers, crystal-burning experiments for empirically determining the radiation sensitivity of a crystal system and the application of mesh scans to find the best location of a crystal to obtain the highest diffraction quality. Beamline users interact with the prepared workflows through a specific brick within the beamline-control GUI MXCuBE

  12. Interpretation of ensembles created by multiple iterative rebuilding of macromolecular models

    International Nuclear Information System (INIS)

    Terwilliger, Thomas C.; Grosse-Kunstleve, Ralf W.; Afonine, Pavel V.; Adams, Paul D.; Moriarty, Nigel W.; Zwart, Peter; Read, Randy J.; Turk, Dusan; Hung, Li-Wei

    2007-01-01

    Heterogeneity in ensembles generated by independent model rebuilding principally reflects the limitations of the data and of the model-building process rather than the diversity of structures in the crystal. Automation of iterative model building, density modification and refinement in macromolecular crystallography has made it feasible to carry out this entire process multiple times. By using different random seeds in the process, a number of different models compatible with experimental data can be created. Sets of models were generated in this way using real data for ten protein structures from the Protein Data Bank and using synthetic data generated at various resolutions. Most of the heterogeneity among models produced in this way is in the side chains and loops on the protein surface. Possible interpretations of the variation among models created by repetitive rebuilding were investigated. Synthetic data were created in which a crystal structure was modelled as the average of a set of ‘perfect’ structures and the range of models obtained by rebuilding a single starting model was examined. The standard deviations of coordinates in models obtained by repetitive rebuilding at high resolution are small, while those obtained for the same synthetic crystal structure at low resolution are large, so that the diversity within a group of models cannot generally be a quantitative reflection of the actual structures in a crystal. Instead, the group of structures obtained by repetitive rebuilding reflects the precision of the models, and the standard deviation of coordinates of these structures is a lower bound estimate of the uncertainty in coordinates of the individual models

  13. MolProbity: all-atom structure validation for macromolecular crystallography

    International Nuclear Information System (INIS)

    Chen, Vincent B.; Arendall, W. Bryan III; Headd, Jeffrey J.; Keedy, Daniel A.; Immormino, Robert M.; Kapral, Gary J.; Murray, Laura W.; Richardson, Jane S.; Richardson, David C.

    2010-01-01

    MolProbity structure validation will diagnose most local errors in macromolecular crystal structures and help to guide their correction. MolProbity is a structure-validation web service that provides broad-spectrum solidly based evaluation of model quality at both the global and local levels for both proteins and nucleic acids. It relies heavily on the power and sensitivity provided by optimized hydrogen placement and all-atom contact analysis, complemented by updated versions of covalent-geometry and torsion-angle criteria. Some of the local corrections can be performed automatically in MolProbity and all of the diagnostics are presented in chart and graphical forms that help guide manual rebuilding. X-ray crystallography provides a wealth of biologically important molecular data in the form of atomic three-dimensional structures of proteins, nucleic acids and increasingly large complexes in multiple forms and states. Advances in automation, in everything from crystallization to data collection to phasing to model building to refinement, have made solving a structure using crystallography easier than ever. However, despite these improvements, local errors that can affect biological interpretation are widespread at low resolution and even high-resolution structures nearly all contain at least a few local errors such as Ramachandran outliers, flipped branched protein side chains and incorrect sugar puckers. It is critical both for the crystallographer and for the end user that there are easy and reliable methods to diagnose and correct these sorts of errors in structures. MolProbity is the authors’ contribution to helping solve this problem and this article reviews its general capabilities, reports on recent enhancements and usage, and presents evidence that the resulting improvements are now beneficially affecting the global database

  14. Assessing Exhaustiveness of Stochastic Sampling for Integrative Modeling of Macromolecular Structures.

    Science.gov (United States)

    Viswanath, Shruthi; Chemmama, Ilan E; Cimermancic, Peter; Sali, Andrej

    2017-12-05

    Modeling of macromolecular structures involves structural sampling guided by a scoring function, resulting in an ensemble of good-scoring models. By necessity, the sampling is often stochastic, and must be exhaustive at a precision sufficient for accurate modeling and assessment of model uncertainty. Therefore, the very first step in analyzing the ensemble is an estimation of the highest precision at which the sampling is exhaustive. Here, we present an objective and automated method for this task. As a proxy for sampling exhaustiveness, we evaluate whether two independently and stochastically generated sets of models are sufficiently similar. The protocol includes testing 1) convergence of the model score, 2) whether model scores for the two samples were drawn from the same parent distribution, 3) whether each structural cluster includes models from each sample proportionally to its size, and 4) whether there is sufficient structural similarity between the two model samples in each cluster. The evaluation also provides the sampling precision, defined as the smallest clustering threshold that satisfies the third, most stringent test. We validate the protocol with the aid of enumerated good-scoring models for five illustrative cases of binary protein complexes. Passing the proposed four tests is necessary, but not sufficient for thorough sampling. The protocol is general in nature and can be applied to the stochastic sampling of any set of models, not just structural models. In addition, the tests can be used to stop stochastic sampling as soon as exhaustiveness at desired precision is reached, thereby improving sampling efficiency; they may also help in selecting a model representation that is sufficiently detailed to be informative, yet also sufficiently coarse for sampling to be exhaustive. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  15. The Temperature Optima and Temperature Sensitivity of Soil Respiration Explained By Macromolecular Rate Theory (MMRT).

    Science.gov (United States)

    Schipper, L. A.; O'Neill, T.; Arcus, V. L.

    2014-12-01

    One of the most fundamental factors controlling all biological and chemical processes is changing temperature. Temperature dependence was originally described by the Arrhenius function in the 19th century. This function provides an excellent description of chemical reaction rates. However, the Arrhenius function does not predict the temperature optimum of biological rates that is clearly evident in laboratory and field measurements. Previously, the temperature optimum of biological processes has been ascribed to denaturation of enzymes but the observed temperature optima in soil are often rather modest, occurring at about 40-50°C and generally less than recognised temperatures for protein unfolding. We have modified the Arrhenius function incorporating a temperature-dependent activation energy derived directly from first principles from thermodynamics of macromolecules. MacroMolecular Rate Theory (MMRT) accounts for large changes in the flexibility of enzymes during catalysis that result in changes in heat capacity (ΔC‡p) of the enzyme during the reaction. MMRT predicts an initially Arrhenius-like response followed by a temperature optimum without the need for enzyme denaturation (Hobbs et al., 2013. ACS Chemical Biology. 8: 2388-2393). Denaturation, of course, occurs at much higher temperatures. We have shown that MMRT fits biogeochemical data collected from laboratory and field studies with important implications for changes in absolute temperature sensitivity as temperature rises (Schipper et al., 2014. Global Change Biology). As the temperature optimum is approached the absolute temperature sensitivity of biological processes decreases to zero. Consequently, the absolute temperature-sensitivity of soil biological processes depends on both the change in ecosystem temperature and the temperature optimum of the biological process. MMRT also very clearly explains why Q10 values decline with increasing temperature more quickly than would be predicted from the

  16. AutoDrug: fully automated macromolecular crystallography workflows for fragment-based drug discovery.

    Science.gov (United States)

    Tsai, Yingssu; McPhillips, Scott E; González, Ana; McPhillips, Timothy M; Zinn, Daniel; Cohen, Aina E; Feese, Michael D; Bushnell, David; Tiefenbrunn, Theresa; Stout, C David; Ludaescher, Bertram; Hedman, Britt; Hodgson, Keith O; Soltis, S Michael

    2013-05-01

    AutoDrug is software based upon the scientific workflow paradigm that integrates the Stanford Synchrotron Radiation Lightsource macromolecular crystallography beamlines and third-party processing software to automate the crystallography steps of the fragment-based drug-discovery process. AutoDrug screens a cassette of fragment-soaked crystals, selects crystals for data collection based on screening results and user-specified criteria and determines optimal data-collection strategies. It then collects and processes diffraction data, performs molecular replacement using provided models and detects electron density that is likely to arise from bound fragments. All processes are fully automated, i.e. are performed without user interaction or supervision. Samples can be screened in groups corresponding to particular proteins, crystal forms and/or soaking conditions. A single AutoDrug run is only limited by the capacity of the sample-storage dewar at the beamline: currently 288 samples. AutoDrug was developed in conjunction with RestFlow, a new scientific workflow-automation framework. RestFlow simplifies the design of AutoDrug by managing the flow of data and the organization of results and by orchestrating the execution of computational pipeline steps. It also simplifies the execution and interaction of third-party programs and the beamline-control system. Modeling AutoDrug as a scientific workflow enables multiple variants that meet the requirements of different user groups to be developed and supported. A workflow tailored to mimic the crystallography stages comprising the drug-discovery pipeline of CoCrystal Discovery Inc. has been deployed and successfully demonstrated. This workflow was run once on the same 96 samples that the group had examined manually and the workflow cycled successfully through all of the samples, collected data from the same samples that were selected manually and located the same peaks of unmodeled density in the resulting difference Fourier

  17. Phase-Separated Liposomes Enhance the Efficiency of Macromolecular Delivery to the Cellular Cytoplasm.

    Science.gov (United States)

    Imam, Zachary I; Kenyon, Laura E; Ashby, Grant; Nagib, Fatema; Mendicino, Morgan; Zhao, Chi; Gadok, Avinash K; Stachowiak, Jeanne C

    2017-10-01

    From viruses to organelles, fusion of biological membranes is used by diverse biological systems to deliver macromolecules across membrane barriers. Membrane fusion is also a potentially efficient mechanism for the delivery of macromolecular therapeutics to the cellular cytoplasm. However, a key shortcoming of existing fusogenic liposomal systems is that they are inefficient, requiring a high concentration of fusion-promoting lipids in order to cross cellular membrane barriers. Toward addressing this limitation, our experiments explore the extent to which membrane fusion can be amplified by using the process of lipid membrane phase separation to concentrate fusion-promoting lipids within distinct regions of the membrane surface. We used confocal fluorescence microscopy to investigate the integration of fusion-promoting lipids into a ternary lipid membrane system that separated into liquid-ordered and liquid-disordered membrane phases. Additionally, we quantified the impact of membrane phase separation on the efficiency with which liposomes transferred lipids and encapsulated macromolecules to cells, using a combination of confocal fluorescence imaging and flow cytometry. Here we report that concentrating fusion-promoting lipids within phase-separated lipid domains on the surfaces of liposomes significantly increases the efficiency of liposome fusion with model membranes and cells. In particular, membrane phase separation enhanced the delivery of lipids and model macromolecules to the cytoplasm of tumor cells by at least 4-fold in comparison to homogenous liposomes. Our findings demonstrate that phase separation can enhance membrane fusion by locally concentrating fusion-promoting lipids on the surface of liposomes. This work represents the first application of lipid membrane phase separation in the design of biomaterials-based delivery systems. Additionally, these results lay the ground work for developing fusogenic liposomes that are triggered by physical and

  18. Right Diaphragm Spontaneous Rupture: A Surgical Approach

    Directory of Open Access Journals (Sweden)

    Duilio Divisi

    2011-01-01

    Full Text Available We present a case of spontaneous rupture of the diaphragm, characterized by nonspecific symptoms. The rapid diagnosis and appropriate surgical approach led to a positive resolution of the pathology.

  19. Spontaneous cecal perforation secondary to acute fulminant ...

    African Journals Online (AJOL)

    Spontaneous cecal perforation secondary to acute fulminant gastroenteritis: report of a rare case. Duvuru Ram, Vilvapathy S. Karthikeyan, Sarath C. Sistla, Sheik M. Ali, Parnandi Sridhar, Nagarajan Rajkumar ...

  20. Spontaneous Trait Inferences on Social Media.

    Science.gov (United States)

    Levordashka, Ana; Utz, Sonja

    2017-01-01

    The present research investigates whether spontaneous trait inferences occur under conditions characteristic of social media and networking sites: nonextreme, ostensibly self-generated content, simultaneous presentation of multiple cues, and self-paced browsing. We used an established measure of trait inferences (false recognition paradigm) and a direct assessment of impressions. Without being asked to do so, participants spontaneously formed impressions of people whose status updates they saw. Our results suggest that trait inferences occurred from nonextreme self-generated content, which is commonly found in social media updates (Experiment 1) and when nine status updates from different people were presented in parallel (Experiment 2). Although inferences did occur during free browsing, the results suggest that participants did not necessarily associate the traits with the corresponding status update authors (Experiment 3). Overall, the findings suggest that spontaneous trait inferences occur on social media. We discuss implications for online communication and research on spontaneous trait inferences.

  1. Spontane abdominale arteriovenøse fistler

    DEFF Research Database (Denmark)

    Flarup, S; Lindholt, Jes Sanddal

    1997-01-01

    Spontaneous arteriovenous fistulas between major abdominal vessels (AAVF) complicates about 1% of abdominal aortic aneurysms. AAVF produces severe circulatory disturbances with high operative mortality. Preoperative diagnosis is important but difficult due to the varied nature of presentation. Fo...

  2. Novel types of DNA-sugar damage in neocarzinostatin cytotoxicity and mutagenesis

    International Nuclear Information System (INIS)

    Goldberg, I.H.

    1986-01-01

    Although a number of antitumor antibiotics interact with DNA to form covalent adducts with the bases, relatively few damage DNA by interacting with the deoxyribose moiety. Neocarzinostatin (NCS), a member of a family of macromolecular antibiotics obtained from filtrates of Streptomyces, is such an agent. Many of the biochemical and cellular effects of NCS resemble those of ionizing radiation. Most, possibly all, of the DNA lesions caused by NCS appear to result from the direct attack of an activated form of the drug on the deoxyribose of DNA. This is to be contrasted with ionizing radiation or the antibiotic bleomycin, that damage DNA deoxyribose through the intervention of a reduced form of oxygen. This paper describes the nature of the interaction between the active component of NCS and DNA, on the mechanism of the ensuing deoxyribose damage, and on some of the biological consequences of these actions. 24 refs., 7 figs

  3. Depressive disorder and grief following spontaneous abortion.

    Science.gov (United States)

    Kulathilaka, Susil; Hanwella, Raveen; de Silva, Varuni A

    2016-04-12

    Abortion is associated with moderate to high risk of psychological problems such as depression, use of alcohol or marijuana, anxiety, depression and suicidal behaviours. The increased risk of depression after spontaneous abortion in Asian populations has not been clearly established. Only a few studies have explored the relationship between grief and depression after abortion. A study was conducted to assess the prevalence and risk factors of depressive disorder and complicated grief among women 6-10 weeks after spontaneous abortion and compare the risk of depression with pregnant women attending an antenatal clinic. Spontaneous abortion group consisted of women diagnosed with spontaneous abortion by a Consultant Obstetrician. Women with confirmed or suspected induced abortion were excluded. The comparison group consisted of randomly selected pregnant, females attending the antenatal clinics of the two hospitals. Diagnosis of depressive disorder was made according to ICD-10 clinical criteria based on a structured clinical interview. This assessment was conducted in both groups. The severity of depressive symptoms were assessed using the Patients Health Questionnaire (PHQ-9). Grief was assessed using the Perinatal Grief Scale which was administered to the women who had experienced spontaneous abortion. The sample consisted of 137 women in each group. The spontaneous abortion group (mean age 30.39 years (SD = 6.38) were significantly older than the comparison group (mean age 28.79 years (SD = 6.26)). There were more females with ≥10 years of education in the spontaneous abortion group (n = 54; SD = 39.4) compared to the comparison group (n = 37; SD = 27.0). The prevalence of depression in the spontaneous abortion group was 18.6 % (95 CI, 11.51-25.77). The prevalence of depression in the comparison group was 9.5 % (95 CI, 4.52-14.46). Of the 64 women fulfilling criteria for grief, 17 (26.6 %) also fulfilled criteria for a depressive episode. The relative risk of

  4. Vector models with spontaneous Lorentz-symmetry breaking

    Science.gov (United States)

    Escobar, C. A.; Urrutia, L. F.

    2018-01-01

    Even though models with spontaneous Lorentz-symmetry breaking also damage gauge invariance, an interesting possibility that emerges is to interpret the resultant massless Goldstone bosons as the gauge bosons of the related gauge theory. In this contribution we review the conditions under which gauge invariance is recovered from such models. To illustrate our general approach we consider the classical Abelian bumblebee and Nambu models. In the former case we prove its connection with electrodynamics by a procedure which takes proper care of the gauge-fixing conditions. In the case of the Abelian Nambu model its relation with electrodynamics is established in such a way that the generalization to the non-Abelian case is straightforward.

  5. Spontaneous retinopathy in HLA-A29 transgenic mice

    Science.gov (United States)

    Szpak, Yann; Vieville, Jean-Claude; Tabary, Thierry; Naud, Marie-Christine; Chopin, Martine; Edelson, Catherine; Cohen, Jacques H. M.; Dausset, Jean; de Kozak, Yvonne; Pla, Marika

    2001-01-01

    Humans who have inherited the class I major histocompatibility allele HLA-A29 have a markedly increased relative risk of developing the eye disease termed birdshot chorioretinopathy. This disease affecting adults is characterized by symmetrically scattered, small, cream-colored spots in the fundus associated with retinal vasculopathy and inflammatory signs causing damage to the ocular structures, leading regularly to visual loss. To investigate the role of HLA-A29 in this disease, we introduced the HLA-A29 gene into mice. Aging HLA-A29 transgenic mice spontaneously developed retinopathy, showing a striking resemblance to the HLA-A29-associated chorioretinopathy. These results strongly suggest that HLA-A29 is involved in the pathogenesis of this disease. Elucidation of the role of HLA-A29 should be assisted by this transgenic model. PMID:11226280

  6. Surgical Outcome in Patients with Spontaneous Supratentorial Intracerebral Hemorrhage

    Directory of Open Access Journals (Sweden)

    Rendevski Vladimir

    2017-12-01

    Full Text Available The aim of the paper was to evaluate the surgical outcome in patients with spontaneous supratentorial intracerebral hemorrhage (ICH after surgical intervention, in respect to the initial clinical conditions, age, sex, hemispheric side and anatomic localization of ICH. Thirty-eight surgically treated patients with spontaneous supratentorial intracerebral hemorrhage were included in the study. The surgical outcome was evaluated three months after the initial admission, according to the Glasgow Outcome Scale (GOS. The surgical treatment was successful in 14 patients (37%, whereas it was unsuccessful in 24 patients (63%. We have detected a significant negative correlation between the Glasgow Coma Scale (GCS scores on admission and the GOS scores after three months, suggesting worse neurological outcome in patients with initially lower GCS scores. The surgical outcome in patients with ICH was not affected by the sex, the hemispheric side and the anatomic localization of ICH, but the age of the patients was estimated as a significant factor for their functional outcome, with younger patients being more likely to be treated successfully. The surgical outcome is affected from the initial clinical state of the patients and their age. The treatment of ICH is still an unsolved clinical problem and the development of new surgical techniques with larger efficiency in the evacuation of the hematoma is necessary, thus making a minimal damage to the normal brain tissue, as well as decreasing the possibility of postoperative bleeding.

  7. Postmenopausal spontaneous uterine perforation: Case report

    Science.gov (United States)

    İşlek Seçen, Elçin; Ağış, Hilal; Altunkaya, Canan; Avşar, Ayşe Filiz

    2015-01-01

    Spontaneous uterine rupture and generalized peritonitis caused by pyometra occurs rarely with high morbidity and mortality. A correct and definite diagnosis can be made with laparotomy or laparoscopy. The clinical findings of perforated pyometra are similar to perforation of the gastrointestinal tract and gynecologic symptoms are less frequent, which makes preoperative diagnosis difficult. We report a case of a patient aged 82 years who underwent surgery for spontaneous uterine rupture and generalized peritonitis as a result of pyometra. PMID:28913055

  8. Endometriosis-related spontaneous diaphragmatic rupture.

    Science.gov (United States)

    Triponez, Frédéric; Alifano, Marco; Bobbio, Antonio; Regnard, Jean-François

    2010-10-01

    Non-traumatic, spontaneous diaphragmatic rupture is a rare event whose pathophysiology is not known. We report the case of endometriosis-related spontaneous rupture of the right diaphragm with intrathoracic herniation of the liver, gallbladder and colon. We hypothesize that the invasiveness of endometriotic tissue caused diaphragm fragility, which finally lead to its complete rupture without traumatic event. The treatment consisted of a classical management of diaphragmatic rupture, with excision of the endometriotic nodule followed by medical ovarian suppression for six months.

  9. Spontaneous regression of metastatic Merkel cell carcinoma.

    LENUS (Irish Health Repository)

    Hassan, S J

    2010-01-01

    Merkel cell carcinoma is a rare aggressive neuroendocrine carcinoma of the skin predominantly affecting elderly Caucasians. It has a high rate of local recurrence and regional lymph node metastases. It is associated with a poor prognosis. Complete spontaneous regression of Merkel cell carcinoma has been reported but is a poorly understood phenomenon. Here we present a case of complete spontaneous regression of metastatic Merkel cell carcinoma demonstrating a markedly different pattern of events from those previously published.

  10. Spontaneous intracranial epidural hematoma during rivaroxaban treatment

    Energy Technology Data Exchange (ETDEWEB)

    Ruschel, Leonardo Gilmone; Rego, Felipe Marques Monteiro do; Milano, Jeronimo Buzetti; Jung, Gustavo Simiano; Silva Junior, Luis Fernando; Ramina, Ricardo, E-mail: leonardoruschel@yahoo.com.br [Instituto de Neurologia de Curitiba (INC), Curitiba, PR (Brazil)

    2016-11-15

    According to our research, this is the first case described in the literature of spontaneous intracranial epidural hematoma secondary to the use of Xarelto®. Spontaneous intracranial epidural hematomas are rarely described in the literature. They are associated with infectious diseases of the skull, coagulation disorders, vascular malformations of the dura mater and metastasis to the skull. Long-term post-marketing monitoring and independent reports will probably detect the full spectrum of hemorrhagic complications of the use of rivaroxaban. (author)

  11. Spontaneous intracranial epidural hematoma during rivaroxaban treatment.

    Science.gov (United States)

    Ruschel, Leonardo Gilmone; Rego, Felipe Marques Monteiro do; Milano, Jerônimo Buzetti; Jung, Gustavo Simiano; Silva, Luis Fernando; Ramina, Ricardo

    2016-11-01

    According to our research, this is the first case described in the literature of spontaneous intracranial epidural hematoma secondary to the use of Xareltor. Spontaneous intracranial epidural hematomas are rarely described in the literature. They are associated with infectious diseases of the skull, coagulation disorders, vascular malformations of the dura mater and metastasis to the skull. Long-term post-marketing monitoring and independent reports will probably detect the full spectrum of hemorrhagic complications of the use of rivaroxaban.

  12. FEL gain optimisation and spontaneous radiation

    Energy Technology Data Exchange (ETDEWEB)

    Bali, L.M.; Srivastava, A.; Pandya, T.P. [Lucknow Univ. (India)] [and others

    1995-12-31

    Colson have evaluated FEL gains for small deviations from perfect electron beam injection, with radiation of the same polarisation as that of the wiggler fields. We find that for optimum gain the polarisation of the optical field should be the same as that of the spontaneous emission under these conditions. With a helical wiggler the axial oscillations resulting from small departures from perfect electron beam injection lead to injection dependent unequal amplitudes and phases of the spontaneous radiation in the two transverse directions. Viewed along the axis therefore the spontaneous emission is elliptically polarised. The azimuth of the ellipse varies with the difference of phase of the two transverse components of spontaneous emission but the eccentricity remains the same. With planar wigglers the spontaneous emission viewed in the axial direction is linearly polarised, again with an injection dependent azimuth. For optimum coherent gain of a radiation field its polarisation characteristics must be the same as those of the spontaneous radiation with both types of wiggler. Thus, with a helical wiggler and the data reported earlier, an increase of 10% in the FEL gain at the fundamental frequency and of 11% at the fifth harmonic has been calculated in the small gain per pass limit. Larger enhancements in gain may result from more favourable values of input parameters.

  13. Spontaneous Extensor Tendon Rupture in the Rheumatoid Wrist: Risk Factors and Preventive Role of Extended Tenosynovectomy.

    Science.gov (United States)

    Hsueh, Jung-Hua; Liu, Wen-Chung; Yang, Kuo-Chung; Hsu, Kuei-Chang; Lin, Cheng-Ta; Chen, Lee-Wei

    2016-03-01

    Spontaneous extensor tendon rupture is often seen in rheumatoid arthritis (RA) patients, but the risk factors are not clearly defined. We therefore collected the data of RA patients with previous extensor tendon rupture and those with tenosynovitis and analyzed the relationship between extended tenosynovectomy and spontaneous extensor tendon rupture. We retrospectively reviewed 17 spontaneous extensor tendon rupture episodes in 15 RA patients and 14 tenosynovitis episodes that required tenosynovectomy in 12 RA patients from 1997 to 2013. Correlations between the incidence of tendon rupture, X-ray findings, and clinical findings in the affected wrists before tendon rupture were analyzed statistically using the test for proportion. The following parameters were significantly correlated with spontaneous extensor tendon rupture: disease duration longer than 8 years, persistent tenosynovitis longer than 1 year duration, and Larsen grade greater than 4 (P = 0.02, 0.03, and 0.01, respectively). Dislocation of the distal end of the ulna, carpal collapse, and the scallop sign on X-ray contributed to a higher spontaneous extensor tendon rupture rate among RA patients (P = 0.01, 0.05, and 0.03, respectively). Extended tenosynovectomy was performed on 14 wrists in 12 RA patients with persistent tenosynovitis longer than 6 months, and Larsen grade did not deteriorate in this group compared with those who did not undergo the surgery. No spontaneous extensor tendon rupture occurred following the surgery. Risk factors of spontaneous extensor tendon rupture included disease duration longer than 8 years, persistent tenosynovitis longer than 1 year, and wrist Larsen grade greater than 4. Dislocation of the distal end of the ulna, carpal collapse, and the scallop sign on X-ray indicated a higher probability of extensor tendon rupture. Rheumatologists should consult with hand surgeons promptly to preserve hand function before tendon rupture. Prophylactic extended tenosynovectomy

  14. Sulfation by human lung fibroblasts: SO4(2-) and sulfur-containing amino acids as sources for macromolecular sulfation.

    Science.gov (United States)

    Elgavish, A; Meezan, E

    1991-06-01

    Studies were carried out in human lung fibroblasts (IMR-90) to investigate 1) the relative contribution of two extracellular pools, inorganic sulfate and sulfur-containing amino acids, to the intracellular fraction precipitable by trichloroacetic acid and 2) the possibility that the transport of these sulfur-containing substrates at the plasma membrane may be a limiting step for macromolecular sulfation. Our studies indicate that the ability to use SO4(2-) released by intracellular catabolism of the sulfur-containing amino acid L-cysteine differs from one cell system to another. In contrast to smooth muscle cells, in the human lung fibroblast, L-cysteine contributes significantly to the intercellular pool of SO4(2-) used for sulfation at extracellular [SO4(2-)] less than 100 microM. However, under physiological conditions with respect to SO4(2-) ([SO4(2-)]0 = 300 microM), L-cysteine does not contribute greater than 30% of the sulfate incorporated into the cellular fraction. Taurine (2-aminoethanesulfonic acid) inhibits SO4(2-) incorporation into the cell-associated macromolecular fraction. However, results suggest that the effect is not due to either SO4(2-) released by its catabolism or to an effect on SO4(2-) transport into the cell. The fact that the transport inhibitor 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid inhibits sulfate incorporation indicates that carrier-mediated sulfate transport at the cellular plasma membrane may be a limiting step for sulfate incorporation. In conclusion, under physiological conditions with respect to SO4(2-), inorganic sulfate is a major source of sulfate for sulfation in human lung fibroblasts and macromolecular sulfation may be limited by its transport into the cells.

  15. Photon-counting single-molecule spectroscopy for studying conformational dynamics and macromolecular interactions

    Energy Technology Data Exchange (ETDEWEB)

    Laurence, Ted Alfred [Univ. of California, Berkeley, CA (United States)

    2002-01-01

    Single-molecule methods have the potential to provide information about conformational dynamics and molecular interactions that cannot be obtained by other methods. Removal of ensemble averaging provides several benefits, including the ability to detect heterogeneous populations and the ability to observe asynchronous reactions. Single-molecule diffusion methodologies using fluorescence resonance energy transfer (FRET) are developed to monitor conformational dynamics while minimizing perturbations introduced by interactions between molecules and surfaces. These methods are used to perform studies of the folding of Chymotrypsin Inhibitor 2, a small, single-domain protein, and of single-stranded DNA (ssDNA) homopolymers. Confocal microscopy is used in combination with sensitive detectors to detect bursts of photons from fluorescently labeled biomolecules as they diffuse through the focal volume. These bursts are analyzed to extract fluorescence resonance energy transfer (FRET) efficiency. Advances in data acquisition and analysis techniques that are providing a more complete picture of the accessible molecular information are discussed. Photon Arrival-time Interval Distribution (PAID) analysis is a new method for monitoring macromolecular interactions by fluorescence detection with simultaneous determination of coincidence, brightness, diffusion time, and occupancy (proportional to concentration) of fluorescently-labeled molecules undergoing diffusion in a confocal detection volume. This method is based on recording the time of arrival of all detected photons, and then plotting the two-dimensional histogram of photon pairs, where one axis is the time interval between each pair of photons 1 and 2, and the second axis is the number of other photons detected in the time interval between photons 1 and 2. PAID is related to Fluorescence Correlation Spectroscopy (FCS) by a collapse of this histogram onto the time interval axis. PAID extends auto- and cross-correlation FCS

  16. Photon-counting single-molecule spectroscopy for studying conformational dynamics and macromolecular interactions

    International Nuclear Information System (INIS)

    Laurence, Ted Alfred

    2002-01-01

    Single-molecule methods have the potential to provide information about conformational dynamics and molecular interactions that cannot be obtained by other methods. Removal of ensemble averaging provides several benefits, including the ability to detect heterogeneous populations and the ability to observe asynchronous reactions. Single-molecule diffusion methodologies using fluorescence resonance energy transfer (FRET) are developed to monitor conformational dynamics while minimizing perturbations introduced by interactions between molecules and surfaces. These methods are used to perform studies of the folding of Chymotrypsin Inhibitor 2, a small, single-domain protein, and of single-stranded DNA (ssDNA) homopolymers. Confocal microscopy is used in combination with sensitive detectors to detect bursts of photons from fluorescently labeled biomolecules as they diffuse through the focal volume. These bursts are analyzed to extract fluorescence resonance energy transfer (FRET) efficiency. Advances in data acquisition and analysis techniques that are providing a more complete picture of the accessible molecular information are discussed. Photon Arrival-time Interval Distribution (PAID) analysis is a new method for monitoring macromolecular interactions by fluorescence detection with simultaneous determination of coincidence, brightness, diffusion time, and occupancy (proportional to concentration) of fluorescently-labeled molecules undergoing diffusion in a confocal detection volume. This method is based on recording the time of arrival of all detected photons, and then plotting the two-dimensional histogram of photon pairs, where one axis is the time interval between each pair of photons 1 and 2, and the second axis is the number of other photons detected in the time interval between photons 1 and 2. PAID is related to Fluorescence Correlation Spectroscopy (FCS) by a collapse of this histogram onto the time interval axis. PAID extends auto- and cross-correlation FCS

  17. Mineral Grains, Dimples, and Hot Volcanic Organic Streams: Dynamic Geological Backstage of Macromolecular Evolution.

    Science.gov (United States)

    Skoblikow, Nikolai E; Zimin, Andrei A

    2018-03-28

    , polycondensation, and formation of proto-cellular structures) are combined within a common dynamic geological process. We suppose macromolecular evolution had an extremely fast, "flash" start: the period from volcanic eruption to formation of lithocyte "populations" took not million years but just several tens of minutes. The scenario proposed can be verified experimentally with a three-module setup working with principles of dynamic (flow) chemistry in its core element.

  18. Enhanced conjugation stability and blood circulation time of macromolecular gadolinium-DTPA contrast agent

    Energy Technology Data Exchange (ETDEWEB)

    Jenjob, Ratchapol [Department of New Drug Development, School of Medicine, Inha University, 2F A-dong, Jeongseok Bldg., Sinheung-dong 3-ga, Jung-gu, Incheon 400-712 (Korea, Republic of); Kun, Na [Department of Biotechnology, The Catholic University of Korea, 43 Jibong-ro, Wonmi-gu, Bucheon-si, Gyeonggi-do 420-743 (Korea, Republic of); Ghee, Jung Yeon [Utah-Inha DDS and Advanced Therapeutics, B-403 Meet-You-All Tower, SongdoTechnopark, 7–50, Songdo-dong, Yeonsu-gu, Incheon 406-840 (Korea, Republic of); Shen, Zheyu; Wu, Xiaoxia [Division of Functional Materials and Nano-Devices, Ningbo Institute of Materials Technology & Engineering (NIMTE), Chinese Academy of Sciences, 519 Zhuangshi Street, Zhenhai District, Ningbo, Zhejiang 315201 (China); Cho, Steve K., E-mail: scho@gist.ac.kr [Division of Liberal Arts and Science, GIST College, Gwangju Institute of Science and Technology, Gwangju 500-712 (Korea, Republic of); Lee, Don Haeng [Utah-Inha DDS and Advanced Therapeutics, B-403 Meet-You-All Tower, SongdoTechnopark, 7–50, Songdo-dong, Yeonsu-gu, Incheon 406-840 (Korea, Republic of); Department of Internal Medicine, School of Medicine, Inha University Hospital, Incheon 420-751 (Korea, Republic of); Yang, Su-Geun, E-mail: Sugeun.Yang@Inha.ac.kr [Department of New Drug Development, School of Medicine, Inha University, 2F A-dong, Jeongseok Bldg., Sinheung-dong 3-ga, Jung-gu, Incheon 400-712 (Korea, Republic of)

    2016-04-01

    In this study, we prepared macromolecular MR T1 contrast agent: pullulan-conjugated Gd diethylene triamine pentaacetate (Gd-DTPA-Pullulan) and estimated residual free Gd{sup 3+}, chelation stability in competition with metal ions, plasma and tissue pharmacokinetics, and abdominal MR contrast on rats. Residual free Gd{sup 3+} in Gd-DTPA-Pullulan was measured using colorimetric spectroscopy. The transmetalation of Gd{sup 3+} incubated with Ca{sup 2+} was performed by using a dialysis membrane (MWCO 100–500 Da) and investigated by ICP-OES. The plasma concentration profiles of Gd-DTPA-Pullulan were estimated after intravenous injection at a dose 0.1 mmol/kg of Gd. The coronal-plane abdominal images of normal rats were observed by MR imaging. The content of free Gd{sup 3+}, the toxic residual form, was less than 0.01%. Chelation stability of Gd-DTPA-Pullulan was estimated, and only 0.2% and 0.00045% of Gd{sup 3+} were released from Gd-DTPA-Pullulan after 2 h incubation with Ca{sup 2+} and Fe{sup 2+}, respectively. Gd-DTPA-Pullulan displayed the extended plasma half-life (t{sub 1/2,α} = 0.43 h, t{sub 1/2,β} = 2.32 h), much longer than 0.11 h and 0.79 h of Gd-EOB-DTPA. Abdominal MR imaging showed Gd-DTPA-Pullulan maintained initial MR contrast for 30 min. The extended plasma half-life of Gd-DTPA-Pullulan probably allows the prolonged MR acquisition time in clinic with enhanced MR contrast. - Highlights: • Macromolecule (pullulan) conjugated Gd contrast agent (Gd-DTPA-Pullulan) showed the extended plasma half-life (t{sub 1/2,α} = 0.43 h, t{sub 1/2,β} = 2.32 h) in comparison with Gd-EOB-DTPA • Gd-DTPA-pullulan T1 contrast agent exhibited strong chelation stability against Gd. • The extended blood circulation attributed the enhanced and prolonged MR contrast on abdominal region of rats. • The extended blood circulation may provide prolonged MR acquisition time window in clinics.

  19. Maintaining Genome Stability in Defiance of Mitotic DNA Damage

    Science.gov (United States)

    Ferrari, Stefano; Gentili, Christian

    2016-01-01

    The implementation of decisions affecting cell viability and proliferation is based on prompt detection of the issue to be addressed, formulation and transmission of a correct set of instructions and fidelity in the execution of orders. While the first and the last are purely mechanical processes relying on the faithful functioning of single proteins or macromolecular complexes (sensors and effectors), information is the real cue, with signal amplitude, duration, and frequency ultimately determining the type of response. The cellular response to DNA damage is no exception to the rule. In this review article we focus on DNA damage responses in G2 and Mitosis. First, we set the stage describing mitosis and the machineries in charge of assembling the apparatus responsible for chromosome alignment and segregation as well as the inputs that control its function (checkpoints). Next, we examine the type of issues that a cell approaching mitosis might face, presenting the impact of post-translational modifications (PTMs) on the correct and timely functioning of pathways correcting errors or damage before chromosome segregation. We conclude this essay with a perspective on the current status of mitotic signaling pathway inhibitors and their potential use in cancer therapy. PMID:27493659

  20. Comparison of two self-assembled macromolecular prodrug micelles with different conjugate positions of SN38 for enhancing antitumor activity

    Directory of Open Access Journals (Sweden)

    Liu Y

    2015-03-01

    Full Text Available Yi Liu,1 Hongyu Piao,1 Ying Gao,1 Caihong Xu,2 Ye Tian,1 Lihong Wang,1 Jinwen Liu,1 Bo Tang,1 Meijuan Zou,1 Gang Cheng1 1Department of Pharmaceutics, Shenyang Pharmaceutical University, Shenyang, Liaoning Province, People’s Republic of China; 2Department of Food Science, Shenyang Normal University, Shenyang, Liaoning Province, People’s Republic of China Abstract: 7-Ethyl-10-hydroxycamptothecin (SN38, an active metabolite of irinotecan (CPT-11, is a remarkably potent antitumor agent. The clinical application of SN38 has been extremely restricted by its insolubility in water. In this study, we successfully synthesized two macromolecular prodrugs of SN38 with different conjugate positions (chitosan-(C10-OHSN38 and chitosan-(C20-OHSN38 to improve the water solubility and antitumor activity of SN38. These prodrugs can self-assemble into micelles in aqueous medium. The particle size, morphology, zeta potential, and in vitro drug release of SN38 and its derivatives, as well as their cytotoxicity, pharmacokinetics, and in vivo antitumor activity in a xenograft BALB/c mouse model were studied. In vitro, chitosan-(C10-OHSN38 (CS-(10sSN38 and chitosan-(C20-OHSN38 (CS-(20sSN38 were 13.3- and 25.9-fold more potent than CPT-11 in the murine colon adenocarcinoma cell line CT26, respectively. The area under the curve (AUC0–24 of SN38 after intravenously administering CS-(10sSN38 and CS-(20sSN38 to Sprague Dawley rats was greatly improved when compared with CPT-11 (both P<0.01. A larger AUC0–24 of CS-(20sSN38 was observed when compared to CS-(10sSN38 (P<0.05. Both of the novel self-assembled chitosan-SN38 prodrugs demonstrated superior anticancer activity to CPT-11 in the CT26 xenograft BALB/c mouse model. We have also investigated the differences between these macromolecular prodrug micelles with regards to enhancing the antitumor activity of SN38. CS-(20sSN38 exhibited better in vivo antitumor activity than CS-(10sSN38 at a dose of 2.5 mg/kg (P<0

  1. Glycogen-graft-poly(2-alkyl-2-oxazolines) - the new versatile biopolymer-based thermoresponsive macromolecular toolbox

    Czech Academy of Sciences Publication Activity Database

    Pospíšilová, Aneta; Filippov, Sergey K.; Bogomolova, Anna; Turner, S.; Sedláček, Ondřej; Matushkin, Nikolai; Černochová, Zulfiya; Štěpánek, Petr; Hrubý, Martin

    2014-01-01

    Roč. 4, č. 106 (2014), s. 61580-61588 ISSN 2046-2069 R&D Projects: GA ČR GA13-08336S; GA MŠk(CZ) LH14079 Grant - others:AV ČR(CZ) M200501201; AV ČR(CZ) ASCR/CONICET 2012CZ006 Program:M Institutional support: RVO:61389013 Keywords : glycogen * poly(2-alkyl-2-oxazoline) * hybrid copolymer Subject RIV: CD - Macromolecular Chemistry Impact factor: 3.840, year: 2014

  2. Structure analysis of molecular systems in the Institute of Macromolecular Chemistry of the Czech Academy of Sciences

    Czech Academy of Sciences Publication Activity Database

    Hašek, Jindřich

    2010-01-01

    Roč. 17, 2a (2010), k32-k34 ISSN 1211-5894. [Struktura 2010. Soláň, 14.06.2010-17.06.2010] R&D Projects: GA AV ČR IAA500500701; GA ČR GA305/07/1073 Institutional research plan: CEZ:AV0Z40500505 Keywords : Academy of Sciences of the Czech Republic * X-ray structure analysis * crystallography Subject RIV: CD - Macromolecular Chemistry http:// xray .cz/ms/bul2010-2a/hasek.pdf

  3. Aging changes of macromolecular synthesis in the digestive organs of mice as revealed by microscopic radioautography and X-ray microanalysis

    Energy Technology Data Exchange (ETDEWEB)

    Nagata, Tetsuji [Shinshu Univ., Matsumoto (Japan). School of Medicine. Dept. of Anatomy and Cell Biology]. E-mail: nagatas@po.cnet.ne.jp

    2002-07-01

    For the purpose of elucidating the aging changes of macromolecular synthesis such as DNA, RNA, proteins, glycoproteins, glycides and lipids in various organ systems of experimental animals, we have studied the digestive organs of aging mice and rats as a series of systematic studies using light and electron microscopic radioautography after incorporations with macromolecular precursors. The experimental animals mainly used were ddY strain mice at various aging groups from embryo to postnatal days 1 and 3, weeks 1 and 2, months 1, 2, 6, 12 up to 2 year senescent stages as well as several groups of adult Wistar rats. The animals were injected with such macromolecular precursors as {sup 3}H - thymidine for DNA, {sup 3}H-uridine for RNA, {sup 3}H-leucine and {sup 3}H proline for proteins, {sup 35}SO{sub 4} for glycoproteins, {sup 3} H-glucosamine for glucides and {sup 3}H-glycerol for lipids. The results demonstrated that these precursors were incorporated into various cell types in the oral cavity, the salivary glands, the esophagus, the stomach, the small and large intestines, the liver and the pancreas at various ages from perinatal to juvenile, mature and senescent stages, showing specific patterns of macromolecular synthesis. It is concluded that these specific patterns of macromolecular synthesis in respective cell types demonstrated the organ specificity of aging of animals. (author)

  4. Spontaneous body movements in spatial cognition

    Directory of Open Access Journals (Sweden)

    Sergiu eTcaci Popescu

    2012-05-01

    Full Text Available People often perform spontaneous body movements during spatial tasks such as giving complex directions or orienting themselves on maps. How are these spontaneous gestures related to spatial problem-solving? We measured spontaneous movements during a perspective-taking task inspired by map reading. Analyzing the motion data to isolate rotation and translation components of motion in specific geometric relation to the task, we found out that most participants executed spontaneous miniature rotations of the head that were significantly related to the main task parameter. These head rotations were as if participants were trying to align themselves with the orientation on the map either in the image plane or on the ground plane, but with tiny amplitudes, typically below 1% of the actual movements. Our results are consistent with a model of sensorimotor prediction driving spatial reasoning. The efference copy of planned movements triggers this prediction mechanism. The movements themselves may then be mostly inhibited; the small spontaneous gestures that we measure are the visible traces of these planned but inhibited actions.

  5. Bilateral spontaneous rupture of 'hale' kidneys

    International Nuclear Information System (INIS)

    Naumov, N.; Zozikov, B.; Otzetov, A.; Kamenova, M.; Martinova, F.; Kalyonski, R.

    2002-01-01

    A rare case of spontaneous bilateral rupture of the kidneys, occurring consecutively over a one-year period in a young male patient with 'hale' kidneys until then, is described. The patient's past history and thorough examination performed do not justify to assign the case under the heading of some of the etiological factors as the underlying cause of spontaneous kidney rupture. The literature survey on spontaneous bilateral non-tumor ruptures of kidneys shows that over a 20-year period, only 3 cases of bilateral spontaneous ruptures have been reported. It is pointed out that panarteritis nodosa followed by hemorrhagic fever with renal syndrome is the commonest underlying cause of such ruptures. Clinically spontaneous ruptures become manifest with emergency condition presenting severe renal colic, impaired to serious general condition, often with acute abdomen and hemodynamic breakdown, and no past history evidence of renal disease or injury. In the initial phase diagnosing is not always easy; it is usually made on the ground of physical examination and the full range of imaging studies used in urological practice and during operative treatment. Emphasis is laid on the fact that the imaging methods are not invariably sufficient to identify the exact etiological factor giving rise to such a severe condition, but nevertheless these methods have an essential practical bearing on diagnosing a rupture. (authors)

  6. Surgical management of spontaneous hypertensive brainstem hemorrhage

    Directory of Open Access Journals (Sweden)

    Bal Krishna Shrestha

    2015-09-01

    Full Text Available Spontaneous hypertensive brainstem hemorrhage is the spontaneous brainstem hemorrhage associated with long term hypertension but not having definite focal or objective lesion. It is a catastrophic event which has a poor prognosis and usually managed conservatively. It is not uncommon, especially in eastern Asian populations, accounting approximately for 10% of the intracerebral hemorrhage. Before the advent of computed tomography, the diagnosis of brainstem hemorrhage was usually based on the clinical picture or by autopsy and believed to be untreatable via surgery. The introduction of computed tomography permitted to categorize the subtypes of brainstem hemorrhage with more predicted outcome. Continuous ongoing developments in the stereotactic surgery and microsurgery have added more specific surgical management in these patients. However, whether to manage conservatively or promptly with surgical evacuation of hematoma is still a controversy. Studies have shown that an accurate prognostic assessment based on clinical and radiological features on admission is critical for establishing a reasonable therapeutic approach. Some authors have advocate conservative management, whereas others have suggested the efficacy of surgical treatment in brainstem hemorrhage. With the widening knowledge in microsurgical techniques as well as neuroimaging technology, there seems to have more optimistic hope of surgical management of spontaneous hypertensive brainstem hemorrhage for better prognosis. Here we present five cases of severe spontaneous hypertensive brainstem hemorrhage patients who had undergone surgery; and explore the possibilities of surgical management in patients with the spontaneous hypertensive brainstem hemorrhage.

  7. Cursed lamp: the problem of spontaneous abortion.

    Science.gov (United States)

    Simkulet, William

    2017-08-09

    Many people believe human fetuses have the same moral status as adult human persons, that it is wrong to allow harm to befall things with this moral status, and thus voluntary, induced abortion is seriously morally wrong. Recently, many prochoice theorists have argued that this antiabortion stance is inconsistent; approximately 60% of human fetuses die from spontaneous abortion, far more than die from induced abortion, so if antiabortion theorists really believe that human fetuses have significant moral status, they have strong moral obligations to oppose spontaneous abortion. Yet, few antiabortion theorists devote any effort to doing so. Many prochoice theorists argue that to resolve this inconsistency, antiabortion theorists should abandon their opposition to induced abortion. Here, I argue that those who do not abandon their opposition to induced abortion but continue to neglect spontaneous abortion act immorally. Aristotle argues that moral responsibility requires both control and awareness; I argue that once an antiabortion theorist becomes aware of the frequency of spontaneous abortion, they have a strong moral obligation to redirect their efforts towards combating spontaneous abortion; failure to do so is morally monstrous. © 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.

  8. Spontaneous preterm birth: advances toward the discovery of genetic predisposition.

    Science.gov (United States)

    Strauss, Jerome F; Romero, Roberto; Gomez-Lopez, Nardhy; Haymond-Thornburg, Hannah; Modi, Bhavi P; Teves, Maria E; Pearson, Laurel N; York, Timothy P; Schenkein, Harvey A

    2018-03-01

    innate immune response (eg, CARD6, CARD8, NLRP10, NLRP12, NOD2, TLR10) and antimicrobial peptide/proteins (eg, DEFB1, MBL2). These findings support the concept that preterm labor, at least in part, has an inflammatory etiology, which can be induced by pathogens (ie, intraamniotic infection) or "danger signals" (alarmins) released during cellular stress or necrosis (ie, sterile intraamniotic inflammation). These findings support the notion that preterm birth has a polygenic basis that involves rare mutations or damaging variants in multiple genes involved in innate immunity and host defense mechanisms against microbes and their noxious products. An overlap among the whole exome sequencing-identified genes and other inflammatory conditions associated with preterm birth, such as periodontal disease and inflammatory bowel disease, was observed, which suggests a shared genetic substrate for these conditions. We propose that whole exome sequencing, as well as whole genome sequencing, is the most promising approach for the identification of functionally significant genetic variants responsible for spontaneous preterm birth, at least in the context of pathologic inflammation. The identification of genes that contribute to preterm birth by whole exome sequencing, or whole genome sequencing, promises to yield valuable population-specific biomarkers to identify the risk for spontaneous preterm birth and potential strategies to mitigate such a risk. Published by Elsevier Inc.

  9. Role of oxidative DNA damage in genome instability and cancer

    International Nuclear Information System (INIS)

    Bignami, M.; Kunkel, T.

    2009-01-01

    Inactivation of mismatch repair (MMR) is associated with a dramatic genomic instability that is observed experimentally as a mutator phenotype and micro satellite instability (MSI). It has been implicit that the massive genetic instability in MMR defective cells simply reflects the accumulation of spontaneous DNA polymerase errors during DNA replication. We recently identified oxidation damage, a common threat to DNA integrity to which purines are very susceptible, as an important cofactor in this genetic instability

  10. Spontaneous Regression of Lumbar Herniated Disc

    Directory of Open Access Journals (Sweden)

    Chun-Wei Chang

    2009-12-01

    Full Text Available Intervertebral disc herniation of the lumbar spine is a common disease presenting with low back pain and involving nerve root radiculopathy. Some neurological symptoms in the majority of patients frequently improve after a period of conservative treatment. This has been regarded as the result of a decrease of pressure exerted from the herniated disc on neighboring neurostructures and a gradual regression of inflammation. Recently, with advances in magnetic resonance imaging, many reports have demonstrated that the herniated disc has the potential for spontaneous regression. Regression coincided with the improvement of associated symptoms. However, the exact regression mechanism remains unclear. Here, we present 2 cases of lumbar intervertebral disc herniation with spontaneous regression. We review the literature and discuss the possible mechanisms, the precipitating factors of spontaneous disc regression and the proper timing of surgical intervention.

  11. Spontaneous hemothorax: primary pleural epithelioid angiosarcoma

    Directory of Open Access Journals (Sweden)

    Amit Panjwani

    2016-01-01

    Full Text Available Spontaneous hemothorax is a rare condition seen in coagulation and vascular disorders. Uncommonly, malignant neoplasms may cause spontaneous hemothorax. Primary pleural epithelioid angiosarcomas (excluding the cases with pleuropulmonary or chest wall involvement are extremely rare pleural tumors, which may be mistaken for mesothelioma or adenocarcinoma, and only 19 cases (one of them from India have been reported in the English literature, to date. It commonly occurs in older men, has a nonspecific clinicoradiological presentation, and carries a poor prognosis with no survivors beyond a year of establishing the diagnosis. We report a case of primary pleural epithelioid angiosarcoma presenting as a life-threatening spontaneous hemothorax. We also present a brief literature review on pleural angiosarcoma.

  12. Computed tomographic findings of spontaneous intracranial hemorrhage

    Energy Technology Data Exchange (ETDEWEB)

    Ko, Seung Sook; Kim, Young Sook; Kim, Young Chul [College of Medicine, Chosun University, Kwangju (Korea, Republic of)

    1987-10-15

    Computed tomography (CT) was a reliable technique to evaluate the exact size and location of spontaneous intracranial hemorrhage and to predict it's prognosis. Fifty-nine cases of spontaneous intracranial hemorrhage were evaluated and reviewed by CT scan. The following results were obtained. 1. The sex ratio of male to female was 1 to 1.4, The highest incidence was in 6th and 7th decades. 2. The most common cause of spontaneous intracranial hemorrhage was hypertension (74.6%), followed by the aneurysm (13.5%), arteriovenous malformation (5.1%), occlusive vascular disease (3.4%), and blood dyscrasia (3.4%). 3. The most common location was basal ganglia and thalamic hemorrhage (37.3%), followed by lobar hemorrhage (27.1%), cerebellar hemorrhage (13.5%), and subarachnoid hemorrhage (11.9%). 4. Primary intraventricular hemorrhage carried the highest mortality. 5. The larger volume of hematoma, the higher the mortality rate.

  13. Spontaneous Perforation of Pyometra: A Case Report

    Directory of Open Access Journals (Sweden)

    2006-01-01

    Full Text Available Pyometra is the accumulation of purulent material in the uterine cavity. Its reported incidence is 0.01–0.5% in gynecologic patients; however, as far as elderly patients are concerned, its incidence is 13.6% [3]. The most common cause of pyometra is malignant diseases of genital tract and the consequences of their treatment (radiotherapy. Other causes are benign tumors like leiomyoma, endometrial polyps, senile cervicitis, cervical occlusion after surgery, puerperal infections, and congenital cervical anomalies. Spontaneous rupture of the uterus is an extremely rare complication of pyometra. To our knowledge, only 21 cases of spontaneous perforation of pyometra have been reported in English literature since 1980. This paper reports an additional case of spontaneous uterine rupture.

  14. Impact damage of composites

    Science.gov (United States)

    Wu, Hsi-Young T.; Springer, George S.

    1986-01-01

    A model is described for estimating the impact damage of fiber reinforced composite plates. The displacements and stresses are calculated by a three dimensional transient, finite element method of solution of the governing equations applicable to a linearly elastic body. The region in which damage occurs is estimated using the Tsai-Wu failure criterion. A computer code was developed which can be used to calculate the impact force, displacements and velocities of the plate and the impact body, stresses and strains in the plate, and the damage area. Sample numerical results are presented illustrating the type of information provided by the code. Comparisons between measured and calculated damage areas are also given.

  15. Implementation of fast macromolecular proton fraction mapping on 1.5 and 3 Tesla clinical MRI scanners: preliminary experience

    Science.gov (United States)

    Yarnykh, V.; Korostyshevskaya, A.

    2017-08-01

    Macromolecular proton fraction (MPF) is a biophysical parameter describing the amount of macromolecular protons involved into magnetization exchange with water protons in tissues. MPF represents a significant interest as a magnetic resonance imaging (MRI) biomarker of myelin for clinical applications. A recent fast MPF mapping method enabled clinical translation of MPF measurements due to time-efficient acquisition based on the single-point constrained fit algorithm. However, previous MPF mapping applications utilized only 3 Tesla MRI scanners and modified pulse sequences, which are not commonly available. This study aimed to test the feasibility of MPF mapping implementation on a 1.5 Tesla clinical scanner using standard manufacturer’s sequences and compare the performance of this method between 1.5 and 3 Tesla scanners. MPF mapping was implemented on 1.5 and 3 Tesla MRI units of one manufacturer with either optimized custom-written or standard product pulse sequences. Whole-brain three-dimensional MPF maps obtained from a single volunteer were compared between field strengths and implementation options. MPF maps demonstrated similar quality at both field strengths. MPF values in segmented brain tissues and specific anatomic regions appeared in close agreement. This experiment demonstrates the feasibility of fast MPF mapping using standard sequences on 1.5 T and 3 T clinical scanners.

  16. A local-optimization refinement algorithm in single particle analysis for macromolecular complex with multiple rigid modules

    Directory of Open Access Journals (Sweden)

    Hong Shan

    2015-12-01

    Full Text Available ABSTRACT Single particle analysis, which can be regarded as an average of signals from thousands or even millions of particle projections, is an efficient method to study the three-dimensional structures of biological macromolecules. An intrinsic assumption in single particle analysis is that all the analyzed particles must have identical composition and conformation. Thus specimen heterogeneity in either composition or conformation has raised great challenges for high-resolution analysis. For particles with multiple conformations, inaccurate alignments and orientation parameters will yield an averaged map with diminished resolution and smeared density. Besides extensive classification approaches, here based on the assumption that the macromolecular complex is made up of multiple rigid modules whose relative orientations and positions are in slight fluctuation around equilibriums, we propose a new method called as local optimization refinement to address this conformational heterogeneity for an improved resolution. The key idea is to optimize the orientation and shift parameters of each rigid module and then reconstruct their three-dimensional structures individually. Using simulated data of 80S/70S ribosomes with relative fluctuations between the large (60S/50S and the small (40S/30S subunits, we tested this algorithm and found that the resolutions of both subunits are significantly improved. Our method provides a proof-of-principle solution for high-resolution single particle analysis of macromolecular complexes with dynamic conformations.

  17. A local-optimization refinement algorithm in single particle analysis for macromolecular complex with multiple rigid modules.

    Science.gov (United States)

    Shan, Hong; Wang, Zihao; Zhang, Fa; Xiong, Yong; Yin, Chang-Cheng; Sun, Fei

    2016-01-01

    Single particle analysis, which can be regarded as an average of signals from thousands or even millions of particle projections, is an efficient method to study the three-dimensional structures of biological macromolecules. An intrinsic assumption in single particle analysis is that all the analyzed particles must have identical composition and conformation. Thus specimen heterogeneity in either composition or conformation has raised great challenges for high-resolution analysis. For particles with multiple conformations, inaccurate alignments and orientation parameters will yield an averaged map with diminished resolution and smeared density. Besides extensive classification approaches, here based on the assumption that the macromolecular complex is made up of multiple rigid modules whose relative orientations and positions are in slight fluctuation around equilibriums, we propose a new method called as local optimization refinement to address this conformational heterogeneity for an improved resolution. The key idea is to optimize the orientation and shift parameters of each rigid module and then reconstruct their three-dimensional structures individually. Using simulated data of 80S/70S ribosomes with relative fluctuations between the large (60S/50S) and the small (40S/30S) subunits, we tested this algorithm and found that the resolutions of both subunits are significantly improved. Our method provides a proof-of-principle solution for high-resolution single particle analysis of macromolecular complexes with dynamic conformations.

  18. Protein crystallography for non-crystallographers, or how to get the best (but not more) from published macromolecular structures

    Science.gov (United States)

    Wlodawer, Alexander; Minor, Wladek; Dauter, Zbigniew; Jaskolski, Mariusz

    2015-01-01

    The number of macromolecular structures deposited in the Protein Data Bank now exceeds 45 000, with the vast majority determined using crystallographic methods. Thousands of studies describing such structures have been published in the scientific literature, and 14 Nobel prizes in chemistry or medicine have been awarded to protein crystallographers. As important as these structures are for understanding the processes that take place in living organisms and also for practical applications such as drug design, many non-crystallographers still have problems with critical evaluation of the structural literature data. This review attempts to provide a brief outline of technical aspects of crystallography and to explain the meaning of some parameters that should be evaluated by users of macromolecular structures in order to interpret, but not over-interpret, the information present in the coordinate files and in their description. A discussion of the extent of the information that can be gleaned from the coordinates of structures solved at different resolution, as well as problems and pitfalls encountered in structure determination and interpretation are also covered. PMID:18034855

  19. Effects of osmolytes and macromolecular crowders on stable GAAA tetraloops and their preference for a CG closing base pair

    Directory of Open Access Journals (Sweden)

    Kaethe N. Leonard

    2018-02-01

    Full Text Available Osmolytes and macromolecular crowders have the potential to influence the stability of secondary structure motifs and alter preferences for conserved nucleic acid sequences in vivo. To further understand the cellular function of RNA we observed the effects of a model osmolyte, polyethylene glycol (PEG 200, and a model macromolecular crowding agent, PEG 8000, on the GAAA tetraloop motif. GAAA tetraloops are conserved, stable tetraloops, and are critical participants in RNA tertiary structure. They also have a thermodynamic preference for a CG closing base pair. The thermal denaturation of model hairpins containing GAAA loops was monitored using UV-Vis spectroscopy in the presence and absence of PEG 200 or PEG 8000. Both of the cosolutes tested influenced the thermodynamic preference for a CG base pair by destabilizing the loop with a CG closing base pair relative to the loop with a GC closing base pair. This result also extended to a related DNA triloop, which provides further evidence that the interactions between the loop and closing base pair are identical for the d(GCA triloop and the GAAA tetraloop. Our results suggest that in the presence of model PEG molecules, loops with a GC closing base pair may retain some preferential interactions with the cosolutes that are lost in the presence of the CG closing base pair. These results reveal that relatively small structural changes could influence how neutral cosolutes tune the stability and function of secondary structure motifs in vivo.

  20. Identification of transcriptional macromolecular associations in human bone using browser based in silico analysis in a giant correlation matrix.

    Science.gov (United States)

    Reppe, Sjur; Sachse, Daniel; Olstad, Ole K; Gautvik, Vigdis T; Sanderson, Paul; Datta, Harish K; Berg, Jens P; Gautvik, Kaare M

    2013-03-01

    Intracellular signaling is critically dependent on gene regulatory networks comprising physical molecular interactions. Presently, there is a lack of comprehensive databases for most human tissue types to verify such macromolecular interactions. We present a user friendly browser which helps to identify functional macromolecular interactions in human bone as significant correlations at the transcriptional level. The molecular skeletal phenotype has been characterized by transcriptome analysis of iliac crest bone biopsies from 84 postmenopausal women through quantifications of ~23,000 mRNA species. When the signal levels were inter-correlated, an array containing >260 million correlations was generated, thus recognizing the human bone interactome at the RNA level. The matrix correlation and p values were made easily accessible by a freely available online browser. We show that significant correlations within the giant matrix are reproduced in a replica set of 13 male vertebral biopsies. The identified correlations differ somewhat from transcriptional interactions identified in cell culture experiments and transgenic mice, thus demonstrating that care should be taken in extrapolating such results to the in vivo situation in human bone. The current giant matrix and web browser are a valuable tool for easy access to the human bone transcriptome and molecular interactions represented as significant correlations at the RNA-level. The browser and matrix should be a valuable hypothesis generating tool for identification of regulatory mechanisms and serve as a library of transcript relationships in human bone, a relatively inaccessible tissue. Copyright © 2012 Elsevier Inc. All rights reserved.

  1. Preclinical imaging and translational animal models of cancer for accelerated clinical implementation of nanotechnologies and macromolecular agents.

    Science.gov (United States)

    De Souza, Raquel; Spence, Tara; Huang, Huang; Allen, Christine

    2015-12-10

    The majority of animal models of cancer have performed poorly in terms of predicting clinical performance of new therapeutics, which are most often first evaluated in patients with advanced, metastatic disease. The development and use of metastatic models of cancer may enhance clinical translatability of preclinical studies focused on the development of nanotechnology-based drug delivery systems and macromolecular therapeutics, potentially accelerating their clinical implementation. It is recognized that the development and use of such models are not without challenge. Preclinical imaging tools offer a solution by allowing temporal and spatial characterization of metastatic lesions. This paper provides a review of imaging methods applicable for evaluation of novel therapeutics in clinically relevant models of advanced cancer. An overview of currently utilized models of oncology in small animals is followed by image-based development and characterization of visceral metastatic cancer models. Examples of imaging tools employed for metastatic lesion detection, evaluation of anti-tumor and anti-metastatic potential and biodistribution of novel therapies, as well as the co-development and/or use of imageable surrogates of response, are also discussed. While the focus is on development of macromolecular and nanotechnology-based therapeutics, examples with small molecules are included in some cases to illustrate concepts and approaches that can be applied in the assessment of nanotechnologies or macromolecules. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. On spontaneous breakdown in Σ-models

    International Nuclear Information System (INIS)

    Ivanov, E.A.

    1975-01-01

    The group theory aspects of spontaneous breakdown in linear Σ-models are discussed. General conditions are formulated under which multiplet of group G (compact or noncompact) is suitable for constructing the Σ-model with a given subgroup of stability of vacuum. It is shown that the Σ-models of spontaneously broken space-time symmetries can be constructed in general only if some extra coordinates are introduced in addition to an ordinary 4-coordinate xsub(μ). The connection between Σ-models of internal symmetries and appropriate nonlinear realizations has also been investigated

  3. Two cases of spontaneous temporal encephalocele.

    Science.gov (United States)

    Kamiya, Kouhei; Mori, Harushi; Kunimatsu, Akira; Kawai, Kensuke; Usami, Kenichi; Ohtomo, Kuni

    2012-12-01

    This is a report of two cases of spontaneous temporal encephalocele: one was anteroinferior and presented with epilepsy; the other was posteroinferior and presented with facial neuritis and labyrinthitis. Spontaneous temporal encephalocele is relatively rare and apparently not familiar to a majority of primary physicians. It may present with a variety of symptoms according to its anatomical location, including cerebrospinal fluid fistulas, recurrent meningitis, chronic otitis media, hearing loss, facial nerve palsy and medically intractable epilepsy. Attention should be paid to this disease entity, as it is easily overlooked in imaging studies and can leave serious neurological deficits. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  4. Spontaneous abortion and physical strain around implantation

    DEFF Research Database (Denmark)

    Hjollund, N H; Jensen, Tina Kold; Bonde, Jens Peter

    2000-01-01

    Existing studies of physical strain and spontaneous abortion are mainly retrospective or based only on pregnancies that have survived the first trimester. Furthermore, almost all studies have relied on averaged measures of physical strain, which tend to blur an effect if peak values during short...... pregnancy the women recorded physical strain prospectively in a structured diary. Physical strain around the time of implantation was associated with later spontaneous abortion. The adjusted risk ratio for women who reported physical strain higher than average at day 6 to 9 after the estimated date...

  5. Need for spontaneous breakdown of chiral symmetry

    International Nuclear Information System (INIS)

    Salomone, A.; Schechter, J.; Tudron, T.

    1981-01-01

    The question of whether the chiral symmetry of the theory of strong interactions (with massless quarks) is required to be spontaneously broken is examined in the framework of a previously discussed effective Lagrangian for quantum chromodynamics. The assumption that physical masses of the theory be finite leads in a very direct way to the necessity of spontaneous breakdown. This result holds for all N/sub F/> or =2, where N/sub F/ is the number of different flavors of light quarks. The atypical cases N/sub F/ = 1,2 are discussed separately

  6. Spontaneous subdural hematoma associated to Duret hemorrhage

    Directory of Open Access Journals (Sweden)

    William Alves Martins, MD

    2015-03-01

    Full Text Available Subdural hematoma (SH is a neurosurgical emergency, usually caused by head trauma. Non-traumatic causes include aneurysm or arterial–venous malformation rupture, coagulopathy and others. We report the case of a 66 year-old man who developed apparently unprovoked signs of increased intracranial pressure. Brain computed tomography scan showed an acute spontaneous SH, surgically treated. Throughout surgery, a ruptured cortical artery with intensive bleeding appeared and was cauterized. After surgery, patient remained comatose and a new CT demonstrated Duret hemorrhage at the brainstem. Acute spontaneous SH of arterial origin is rare and highly lethal, in which a good prognosis relies on early diagnosis and treatment.

  7. Primer on spontaneous heating and pyrophoricity

    Energy Technology Data Exchange (ETDEWEB)

    1994-12-01

    This primer was prepared as an information resource for personnel responsible for operation of DOE nuclear facilities. It has sections on combustion principles, spontaneous heating/ignition of hydrocarbons and organics, pyrophoric gases and liquids, pyrophoric nonmetallic solids, pyrophoric metals (including Pu and U), and accident case studies. Although the information in this primer is not all-encompassing, it should provide the reader with a fundamental knowledge level sufficient to recognize most spontaneous combustion hazards and how to prevent ignition and widespread fires. This primer is provided as an information resource only, and is not intended to replace any fire protection or hazardous material training.

  8. Cavity enhanced rephased amplified spontaneous emission

    International Nuclear Information System (INIS)

    A Williamson, Lewis; J Longdell, Jevon

    2014-01-01

    Amplified spontaneous emission is usually treated as an incoherent noise process. Recent theoretical and experimental work using rephasing optical pulses has shown that rephased amplified spontaneous emission (RASE) is a potential source of wide bandwidth time-delayed entanglement. Due to poor echo efficiency the plain RASE protocol does not in theory achieve perfect entanglement. Experiments done to date show a very small amount of entanglement at best. Here we show that RASE can, in principle, produce perfect multimode time-delayed two mode squeezing when the active medium is placed inside a Q-switched cavity. (paper)

  9. Spontaneous supersymmetry breaking on the lattice

    Energy Technology Data Exchange (ETDEWEB)

    Wenger, Urs [Albert Einstein Center for Fundamental Physics, Institute for Theoretical Physics, University of Bern, Sidlerstrasse 5, CH-3012 Bern (Switzerland)

    2013-07-01

    We discuss various strategies for regularising supersymmetric quantum field theories on a space-time lattice. In general, simulations of lattice models with spontaneously broken supersymmetry suffer from a fermion sign problem related to the vanishing of the Witten index. We discuss a novel approach which evades this problem in low dimensions by formulating the path integral on the lattice in terms of fermion loops. Then we present exact results on the spectrum and the Witten index for N=2 supersymmetric quantum mechanics and results from simulations of the spontaneously broken N=1 Wess-Zumino model.

  10. Damage Theory Validation

    DEFF Research Database (Denmark)

    Simonsen, Bo Cerup

    1998-01-01

    This report contains a series of validation examples for the theoretical model implemented in the computer program DAMAGE. note that the validation examples are for assembled structures.......This report contains a series of validation examples for the theoretical model implemented in the computer program DAMAGE. note that the validation examples are for assembled structures....

  11. DNA damage and autophagy

    International Nuclear Information System (INIS)

    Rodriguez-Rocha, Humberto; Garcia-Garcia, Aracely; Panayiotidis, Mihalis I.; Franco, Rodrigo

    2011-01-01

    Both exogenous and endogenous agents are a threat to DNA integrity. Exogenous environmental agents such as ultraviolet (UV) and ionizing radiation, genotoxic chemicals and endogenous byproducts of metabolism including reactive oxygen species can cause alterations in DNA structure (DNA damage). Unrepaired DNA damage has been linked to a variety of human disorders including cancer and neurodegenerative disease. Thus, efficient mechanisms to detect DNA lesions, signal their presence and promote their repair have been evolved in cells. If DNA is effectively repaired, DNA damage response is inactivated and normal cell functioning resumes. In contrast, when DNA lesions cannot be removed, chronic DNA damage triggers specific cell responses such as cell death and senescence. Recently, DNA damage has been shown to induce autophagy, a cellular catabolic process that maintains a balance between synthesis, degradation, and recycling of cellular components. But the exact mechanisms by which DNA damage triggers autophagy are unclear. More importantly, the role of autophagy in the DNA damage response and cellular fate is unknown. In this review we analyze evidence that supports a role for autophagy as an integral part of the DNA damage response.

  12. Animal damage management handbook.

    Science.gov (United States)

    Hugh C. Black

    1994-01-01

    This handbook treats animal damage management (ADM) in the West in relation to forest, range, and recreation resources; predator management is not addressed. It provides a comprehensive reference of safe, effective, and practical methods for managing animal damage on National Forest System lands. Supporting information is included in references after each chapter and...

  13. Animal damage to birch

    Science.gov (United States)

    James S. Jordan; Francis M. Rushmore

    1969-01-01

    A relatively few animal species are responsible for most of the reported damage to the birches. White-tailed deer, yellow-bellied sapsuckers, porcupines, moose, and hares are the major animals involved. We will review reports of damage, discuss the underlying causes, and describe possible methods of control. For example, heavy deer browsing that eliminates birch...

  14. Nuclear damage - civil liability

    International Nuclear Information System (INIS)

    Simoes, A.C.

    1980-01-01

    An analysis is made of the civil liability for nuclear damage since there is a need to adjust the existing rules to the new situations created. The conventions that set up the new disciplining rules not considered in the common law for the liability of nuclear damage are also mentioned. (A.L.) [pt

  15. Consumption of a dark roast coffee decreases the level of spontaneous DNA strand breaks: a randomized controlled trial.

    Science.gov (United States)

    Bakuradze, T; Lang, R; Hofmann, T; Eisenbrand, G; Schipp, D; Galan, J; Richling, E

    2015-02-01

    Coffee consumption has been reported to decrease oxidative damage in peripheral white blood cells (WBC). However, effects on the level of spontaneous DNA strand breaks, a well established marker of health risk, have not been specifically reported yet. We analyzed the impact of consuming a dark roast coffee blend on the level of spontaneous DNA strand breaks. Healthy men (n = 84) were randomized to consume daily for 4 weeks either 750 ml of fresh coffee brew or 750 ml of water, subsequent to a run in washout phase of 4 weeks. The study coffee was a blend providing high amounts of both caffeoylquinic acids (10.18 ± 0.33 mg/g) and the roast product N-methylpyridinium (1.10 ± 0.05 mg/g). Before and after the coffee/water consumption phase, spontaneous strand breaks were determined by comet assay. At baseline, both groups exhibited a similar level of spontaneous DNA strand breaks. In the intervention phase, spontaneous DNA strand breaks slightly increased in the control (water only) group whereas they significantly decreased in the coffee group, leading to a 27% difference within both arms (p = 0.0002). Food frequency questionnaires indicated no differences in the overall diet between groups, and mean body weight during the intervention phases remained stable. The consumption of the study coffee substantially lowered the level of spontaneous DNA strand breaks in WBC. We conclude that regular coffee consumption contributes to DNA integrity.

  16. Wheaten ferments spontaneous fermantation in biotechnological methods

    OpenAIRE

    KAKHRAMON SANOQULOVICH RAKHMONOV; ISABAEV ISMAIL BABADJANOVICH

    2016-01-01

    In article are shown results of research of biotechnological properties of wheaten leavens of spontaneous fermentation (in the example of pea-anisetree leaven) and their analysis. Also is established influence of the given type of leavens on the basic biopolymers of the flour, on the property of the pastry and quality of bread from wheaten flour.

  17. Original article Spontaneous Pregnancy Outcome after Surgical ...

    African Journals Online (AJOL)

    2011-09-28

    Sep 28, 2011 ... Table 2: Spontaneous pregnancy in relation to postoperative semen parameters. (no statistically significant difference), comparable to the mean ages of 22, 28.4 and. 34.9 years, respectively, reported by Bach et al9, Abdel- Meguid et al10 and Baazeem et al11. The mean age of the wives who did or did.

  18. Spontaneous symmetry breakdown in gauge theories

    International Nuclear Information System (INIS)

    Scadron, M.D.

    1982-01-01

    The dynamical theory of spontaneous breakdown correctly predicts the bound states and relates the order parameters of electron-photon superconductivity and quark-gluon chiral symmetry. A similar statement cannot be made for the standard electro-weak gauge symmetry. (author)

  19. Identical Twin Primigravid Sisters -Spontaneous Labour and ...

    African Journals Online (AJOL)

    We report 2 cases of identical twin sisters, the older sibling getting married 14 months earlier but both got pregnant for their first child at about the same time and were managed by the same Obstetrician and fell into spontaneous labour within a few hours of each other. Both were delivered by emergency caesarean section ...

  20. SPONTANEOUS CP VIOLATION AND QUARK MASS AMBIGUITIES.

    Energy Technology Data Exchange (ETDEWEB)

    CREUTZ,M.

    2004-09-21

    I explore the regions of quark masses where CP will be spontaneously broken in the strong interactions. The boundaries of these regions are controlled by the chiral anomaly, which manifests itself in ambiguities in the definition of non-degenerate quark masses. In particular, the concept of a single massless quark is ill defined.

  1. 1 INFLUENCE OF SPONTANEOUS FERMENTATION ON SOME ...

    African Journals Online (AJOL)

    RopSvr

    Spontaneous fermentation has been identified to improve the quality characteristics of foods derived from them. When combined with cowpea fortification and nixtamalization, it is expected to improve the nutritional, functional, physico-chemical and sensory qualities of maize based foods thereby improving the qualities as ...

  2. Association between Nutritional Status with Spontaneous Abortion

    Directory of Open Access Journals (Sweden)

    Rahimeh Ahmadi

    2016-11-01

    Full Text Available Background: Spontaneous abortion is the most common adverse pregnancy outcome. We aimed to investigate a possible link between nutrient deficiencies and the risk of spontaneous abortion. Materials and Methods: This case-control study included the case group (n=331 experiencing a spontaneous abortion before 14 weeks of pregnancy and the control group (n=331 who were healthy pregnant women over 14 weeks of pregnancy. The participants filled out Food Frequency Questionnaire (FFQ, in which they reported their frequency of consumption for a given serving of each food item during the past three months, on a daily, weekly or monthly basis. The reported frequency for each food item was converted to a daily intake. Then, consumption of nutrients was compared between the two groups. Results: There are significant differences between the two groups regarding consumed servings/day of vegetables, bread and cereal, meat, poultry, fish, eggs, beans, fats, oils and dairy products (P=0.012, P<0.001, P=0.004, P<0.001, P=0.019, respectively. There are significant differences between the two groups in all micronutrient including folic acid, iron, vitamin C, vitamin B6, vitamin B12 and zinc (P<0.001. Conclusion: Poor nutrientions may be correlated with increased risk of spontaneous abortion

  3. Spontaneous regression of an intraspinal disc cyst

    Energy Technology Data Exchange (ETDEWEB)

    Demaerel, P.; Eerens, I.; Wilms, G. [University Hospital, Leuven (Belgium). Dept. of Radiology; Goffin, J. [Dept. of Neurosurgery, University Hospitals, Leuven (Belgium)

    2001-11-01

    We present a patient with a so-called disc cyst. Its location in the ventrolateral epidural space and its communication with the herniated disc are clearly shown. The disc cyst developed rapidly and regressed spontaneously. This observation, which has not been reported until now, appears to support focal degeneration with cyst formation as the pathogenesis. (orig.)

  4. Spontaneous rupture of an infected renal cyst

    Energy Technology Data Exchange (ETDEWEB)

    Kopp, W.; Toelly, E.; Ebner, F.; Kullnig, P.

    1986-07-01

    Spontaneous or traumatic rupture of renal cysts is a rare occurrence. The contents of the cyst can perforate into the renal calyx system or into the perirenal space. Perforation into the peritoneal cavity has also been described (1, 2, 4, 5).

  5. Proteomic Biomarkers for Spontaneous Preterm Birth

    DEFF Research Database (Denmark)

    Kacerovsky, Marian; Lenco, Juraj; Musilova, Ivana

    2014-01-01

    This review aimed to identify, synthesize, and analyze the findings of studies on proteomic biomarkers for spontaneous preterm birth (PTB). Three electronic databases (Medline, Embase, and Scopus) were searched for studies in any language reporting the use of proteomic biomarkers for PTB published...

  6. Spontaneous emission from saturated parametric amplifiers

    DEFF Research Database (Denmark)

    Rottwitt, Karsten; Ott, Johan Raunkjær; Steffensen, Henrik

    2009-01-01

    Noise performance of parametric amplifiers is typically calculated assuming un-depleted operation. However, in many applications especially when applied as regenerative amplifiers in systems based on phase shift keyed modulation schemes, this assumption is not valid. Here we show the impact...... on accumulated spontaneous emission for a parametric amplifier operated in saturation....

  7. Spontaneous Non-verbal Counting in Toddlers

    Science.gov (United States)

    Sella, Francesco; Berteletti, Ilaria; Lucangeli, Daniela; Zorzi, Marco

    2016-01-01

    A wealth of studies have investigated numerical abilities in infants and in children aged 3 or above, but research on pre-counting toddlers is sparse. Here we devised a novel version of an imitation task that was previously used to assess spontaneous focusing on numerosity (i.e. the predisposition to grasp numerical properties of the environment)…

  8. Editorial: Spontaneous bacterial peritonitis | Lule | East African ...

    African Journals Online (AJOL)

    Journal Home > Vol 81, No 3 (2004) >. Log in or Register to get access to full text downloads. Username, Password, Remember me, or Register. Editorial: Spontaneous bacterial peritonitis. GN Lule. Abstract. No Abstract Available. Full Text: EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT · DOWNLOAD FULL TEXT ...

  9. Spontaneous conversion of first onset atrial fibrillation

    DEFF Research Database (Denmark)

    Lindberg, Søren Østergaard; Hansen, Sidsel; Nielsen, Tonny

    2011-01-01

    Background  We studied all patients admitted to hospital with first onset atrial fibrillation (AF) to determine the probability of spontaneous conversion to sinus rhythm and to identify factors predictive of such a conversion. Methods and Results  We retrospectively reviewed charts of 438...

  10. Spontaneous dimensional reduction in quantum gravity

    Science.gov (United States)

    Carlip, S.

    2016-07-01

    Hints from a number of different approaches to quantum gravity point to a phenomenon of “spontaneous dimensional reduction” to two spacetime dimensions near the Planck scale. I examine the physical meaning of the term “dimension” in this context, summarize the evidence for dimensional reduction, and discuss possible physical explanations.

  11. Surgical management of spontaneous ruptured hepatocellular adenoma

    Directory of Open Access Journals (Sweden)

    Marcelo Augusto Fontenelle Ribeiro Junior

    2009-01-01

    Full Text Available AIMS: Spontaneous ruptured hepatocellular adenoma (SRHA is a rare life-threatening condition that may require surgical treatment to control hemorrhaging and also stabilize the patient. We report a series of emergency surgeries performed at our institution for this condition. METHODS: We reviewed medical records and radiology files of 28 patients (from 1989 to 2006 with a proven diagnosis of hepatocellular adenoma (HA. Three (10.7% of 28 patients had spontaneous ruptured hepatocellular adenoma, two of which were associated with intrahepatic hemorrhage while one had intraperitoneal bleeding. Two patients were female and one was male. Both female patients had a background history of oral contraceptive use. Sudden abdominal pain associated with hemodynamic instability occurred in all patients who suffered from spontaneous ruptured hepatocellular adenoma. The mean age was 41.6 years old. The preoperative assessment included liver function tests, ultrasonography and computed tomography. RESULTS: The surgical approaches were as follows: right hemihepatectomy for controlling intraperitoneal bleeding, and right extended hepatectomy and non-anatomic resection of the liver for intrahepatic hemorrhage. There were no deaths, and the postoperative complications were bile leakage and wound infection (re-operation, as well as intraperitoneal abscess (re-operation and pleural effusion. CONCLUSION: Spontaneous ruptured hepatocellular adenoma may be treated by surgery for controlling hemorrhages and stabilizing the patient, and the decision to operate depends upon both the patient's condition and the expertise of the surgical team.

  12. Chronic Allium sativum administration alters spontaneous ...

    African Journals Online (AJOL)

    This study was conducted to investigate the effects of Allium sativum extract on the medial prefrontal cortex and neurobehaviour of adult Wistar rats. ... altered spontaneous alternation, while cellular pathologic changes were observed in the medial prefrontal cortex of these test groups in a dose dependent sequence.

  13. Spontaneous hedonic reactions to social media cues

    NARCIS (Netherlands)

    Koningsbruggen, G.M. van; Hartmann, T.; Eden, A.; Veling, H.P.

    2017-01-01

    Why is it so difficult to resist the desire to use social media? One possibility is that frequent social media users possess strong and spontaneous hedonic reactions to social media cues, which, in turn, makes it difficult to resist social media temptations. In two studies (total N = 200), we

  14. Recurrent spontaneous intracerebral hemorrhage associated with ...

    African Journals Online (AJOL)

    Spontaneous intracerebral hemorrhage (ICH) accounts for 15% of stroke cases in the US and Europe and up to 30% in Asian populations. Intracerebral hemorrhage is a relatively uncommon form of stroke-it causes only 10 to 15 percent of all strokes. It is more disabling and has a higher mortality rate than ischemic stroke, ...

  15. Ovarian hyperstimulation syndrome in a spontaneous pregnancy ...

    African Journals Online (AJOL)

    It is known that most cases of Ovarian Hyperstimulation Syndrome (OHSS) are associated with the therapies for ovulation induction. However, OHSS may rarely be associated with a spontaneous ovulatory cycle, usually in the case of multiple gestations, hypothyroidism or polycystic ovary syndrome. We report a case of ...

  16. Spontaneous left main coronary artery dissection

    Directory of Open Access Journals (Sweden)

    Alptug Tokatli

    2016-03-01

    Full Text Available Spontaneous coronary artery dissection (SCAD is a very rare clinical condition. Physiopathology of SCAD is still mostly unclear. Clinical presentation of SCAD ranges from atypical symptoms to sudden cardiac death. The diagnosis of dissection is generally made by using conventional coronary angiography. Invasive or conservative treatment is reasonable.

  17. Spontaneous extracranial decompression of epidural hematoma

    International Nuclear Information System (INIS)

    Neely, John C.; Jones, Blaise V.; Crone, Kerry R.

    2008-01-01

    Epidural hematoma (EDH) is a common sequela of head trauma in children. An increasing number are managed nonsurgically, with close clinical and imaging observation. We report the case of a traumatic EDH that spontaneously decompressed into the subgaleal space, demonstrated on serial CT scans that showed resolution of the EDH and concurrent enlargement of the subgaleal hematoma. (orig.)

  18. Spontaneous extracranial decompression of epidural hematoma

    Energy Technology Data Exchange (ETDEWEB)

    Neely, John C. [Marshall University School of Medicine, Huntington, WV (United States); Jones, Blaise V. [Cincinnati Children' s Hospital Medical Center, Department of Radiology, Cincinnati, OH (United States); Crone, Kerry R. [Cincinnati Children' s Hospital Medical Center, Division of Neurosurgery, Cincinnati, OH (United States)

    2008-03-15

    Epidural hematoma (EDH) is a common sequela of head trauma in children. An increasing number are managed nonsurgically, with close clinical and imaging observation. We report the case of a traumatic EDH that spontaneously decompressed into the subgaleal space, demonstrated on serial CT scans that showed resolution of the EDH and concurrent enlargement of the subgaleal hematoma. (orig.)

  19. Spontaneous Sourcing among Students Reading Multiple Documents

    Science.gov (United States)

    Stromso, Helge I.; Braten, Ivar; Britt, M. Anne; Ferguson, Leila E.

    2013-01-01

    This study used think-aloud methodology to explore undergraduates' spontaneous attention to and use of source information while reading six documents that presented conflicting views on a controversial social scientific issue in a Google-like environment. Results showed that students explicitly and implicitly paid attention to sources of documents…

  20. Massive Spontaneous Hemothorax, Giant Intrathoracic Meningocele ...

    African Journals Online (AJOL)

    haemothorax associated with von Recklinghausen's disease: Review of occurrence in Japan. Thorax 1997;52:575‑8. 3. Fedoruk LM, English J, Fradet GJ. Spontaneous hemothorax and neurofibromatosis: A review of a lethal combination. Asian Cardiovasc. Thorac Ann 2007;15:342‑4. 4. Conlon NP, Redmond KC, Celi LA.

  1. A Fatal Complication of Dermatomyositis: Spontaneous Pneumomediastinum

    Directory of Open Access Journals (Sweden)

    Ezgi Demirdöğen Çetinoğlu

    2016-04-01

    Full Text Available Interstitial lung disease (ILD is a negative prognostic factor associated with increased morbidity and mortality in patients with dermatomyositis (DM. Spontaneous pneumomediastinum is a rare complication of DM and it can be fatal. We present a 48-year-old woman with DM and ILD complicated by pneumomediastinum without pneumothorax and subcutaneous emphysema.

  2. Grooming behavior of spontaneously hypertensive rats

    NARCIS (Netherlands)

    Buuse, M. van den; Jong, Wybren de

    1987-01-01

    In an open field spontaneously hypertensive rats (SHR) exhibited lower scores for grooming when compared to their normotensive controls, the Wistar Kyoto rats (WKY). After i.c.v. injection of 1 μg ACTH1–24 cumulative 50-min grooming scores were lower in SHR. Analysis of subscores indicated that the

  3. Spontaneous abortion and physical strain around implantation

    DEFF Research Database (Denmark)

    Hjollund, N H; Jensen, Tina Kold; Bonde, Jens Peter

    2000-01-01

    Existing studies of physical strain and spontaneous abortion are mainly retrospective or based only on pregnancies that have survived the first trimester. Furthermore, almost all studies have relied on averaged measures of physical strain, which tend to blur an effect if peak values during short ...

  4. Spontaneous Hedonic Reactions to Social Media Cues.

    Science.gov (United States)

    van Koningsbruggen, Guido M; Hartmann, Tilo; Eden, Allison; Veling, Harm

    2017-05-01

    Why is it so difficult to resist the desire to use social media? One possibility is that frequent social media users possess strong and spontaneous hedonic reactions to social media cues, which, in turn, makes it difficult to resist social media temptations. In two studies (total N = 200), we investigated less-frequent and frequent social media users' spontaneous hedonic reactions to social media cues using the Affect Misattribution Procedure-an implicit measure of affective reactions. Results demonstrated that frequent social media users showed more favorable affective reactions in response to social media (vs. control) cues, whereas less-frequent social media users' affective reactions did not differ between social media and control cues (Studies 1 and 2). Moreover, the spontaneous hedonic reactions to social media (vs. control) cues were related to self-reported cravings to use social media and partially accounted for the link between social media use and social media cravings (Study 2). These findings suggest that frequent social media users' spontaneous hedonic reactions in response to social media cues might contribute to their difficulties in resisting desires to use social media.

  5. Spontaneous electric fields in solid films: spontelectrics

    DEFF Research Database (Denmark)

    Field, David; Plekan, Oksana; Cassidy, Andrew

    2013-01-01

    When dipolar gases are condensed at sufficiently low temperature onto a solid surface, they form films that may spontaneously exhibit electric fields in excess of 108V/m. This effect, called the ‘spontelectric effect’, was recently revealed using an instrument designed to measure scattering...

  6. Spontaneous Retroperitoneal Hemorrhage from Adrenal Artery Aneurysm

    International Nuclear Information System (INIS)

    Gonzalez Valverde, F.M.; Balsalobre, M.; Torregrosa, N.; Molto, M.; Gomez Ramos, M.J.; Vazquez Rojas, J.L.

    2007-01-01

    Spontaneous adrenal hemorrhage is a very rare but serious disorder of the adrenal gland that can require emergent treatment. We report on a 42-year-old man who underwent selective angiography for diagnosis and treatment of retroperitoneal hemorrhage from small adrenal artery aneurysm. This case gives further details about the value of transluminal artery embolization in the management of visceral aneurysm rupture

  7. Individual differences in spontaneous analogical transfer.

    Science.gov (United States)

    Kubricht, James R; Lu, Hongjing; Holyoak, Keith J

    2017-05-01

    Research on analogical problem solving has shown that people often fail to spontaneously notice the relevance of a semantically remote source analog when solving a target problem, although they are able to form mappings and derive inferences when given a hint to recall the source. Relatively little work has investigated possible individual differences that predict spontaneous transfer, or how such differences may interact with interventions that facilitate transfer. In this study, fluid intelligence was measured for participants in an analogical problem-solving task, using an abridged version of the Raven's Progressive Matrices (RPM) test. In two experiments, we systematically compared the effect of augmenting verbal descriptions of the source with animations or static diagrams. Solution rates to Duncker's radiation problem were measured across varying source presentation conditions, and participants' understanding of the relevant source material was assessed. The pattern of transfer was best fit by a moderated mediation model: the positive impact of fluid intelligence on spontaneous transfer was mediated by its influence on source comprehension; however, this path was in turn modulated by provision of a supplemental animation via its influence on comprehension of the source. Animated source depictions were most beneficial in facilitating spontaneous transfer for those participants with low scores on the fluid intelligence measure.

  8. Spontaneous regression of a mandibular arteriovenous malformation

    Directory of Open Access Journals (Sweden)

    Scott B. Raymond, MD, PhD

    2015-06-01

    Full Text Available Mandibular arteriovenous malformations (AVMs are rare lesions that may initially present as catastrophic bleeding during dental surgical procedures. Owing to the significant risk of bleeding, most mandibular AVMs are treated definitively by resection or embolization. In this report, we describe a mandibular AVM that spontaneously regressed after biopsy.

  9. Unified gauge theories with spontaneous symmetry breaking

    International Nuclear Information System (INIS)

    MacDowell, S.W.

    1975-01-01

    Unified gauge theories with spontaneous symmetry breaking are studied with a view to renormalize quantum field theory. Georgi-Glashow and Weinberg-Salam models to unify weak and electromagnetic interactions are discussed in detail. Gauge theories of strong interactions are also considered [pt

  10. Influence of spontaneous fermentation on some quality ...

    African Journals Online (AJOL)

    Spontaneous fermentation has been identified to improve the quality characteristics of foods derived from them. When combined with cowpea fortification and nixtamalization, it is expected to improve the nutritional, functional, physico- chemical and sensory qualities of maize based foods thereby improving the qualities as ...

  11. Maternal Factors Associated With Early Spontaneous Singleton ...

    African Journals Online (AJOL)

    Background: Knowledge of the maternal factors predisposing to preterm deliveries should affect the anticipatory care of mothers at risk of delivering preterm babies and improve perinatal outcome. Objective: To determine the maternal socio-biological characteristics associated with the delivery of early spontaneous ...

  12. PERIODIC-SOLUTIONS IN SPONTANEOUSLY BROKEN THEORIES

    NARCIS (Netherlands)

    BRIHAYE, Y; KUNZ, J

    A class of spontaneously broken field theories is proposed, and the occurrence of their periodic, classical solutions is investigated in detail. The emergence of multiple solutions is observed, their normal modes of oscillation are studied, and the bifurcations of the classical energy functional are

  13. Relation between some environmental pollutants and recurrent spontaneous abortion

    Directory of Open Access Journals (Sweden)

    Aziza A. Saad

    2016-09-01

    Full Text Available Reproductive health is exquisitely sensitive to characteristics of an individual’s environment including physical, biological, behavioral, cultural and socioeconomic factors. This study was launched to elucidate the effect of the exposure to chemical pollutants as aromatic amines viz. (benzidine, mono-acetyl benzidine, diacetyl benzidine, α,β-naphthylamine as well as the biological pollutants e.g., human cytomegalovirus (HCMV as risk factors for recurrent spontaneous abortion (RSA through determination of MDA as a marker of oxidative stress and determination of some antioxidant markers. The results of the current study revealed that the aborter mothers were being exposed to environmental pollutants as aromatic amines which were manifested by the presence of benzidine, mono-acetyl-benzidine, di-acetyl-benzidine, α,β-naphthylamine in most of their urine samples, where the level of aromatic amines were more 13.6, 10, 15, and 4-folds than the control group, respectively. Also, the data suggest that in early pregnancy failure there is an increase in markers of oxidative stress and a probable decrease in maternal antioxidant defenses (22 nmol/ml and 17 mg/l, 550 U/l, respectively. Generation of ROS in large quantities, in the first trimester placenta which has limited antioxidant defenses may cause DNA damage, oxidation of protein and lipid resulting in extensive cell death. Also, it was demonstrated that high elevation of HCMV inhibits cytotrophoblasts proliferation, migration invasion and matrix metalloproteins (MMP expression. Obviously, placental toxicological responses are partly due to pharmaco/toxico dynamic responses to the chemicals. Conclusively, the aforementioned findings emphasis that, the exposures to environmental chemical and/or biological risk factors are implicated in the pathogenesis of recurrent spontaneous abortion.

  14. Spontaneous sensorimotor coupling with multipart music.

    Science.gov (United States)

    Hurley, Brian K; Martens, Peter A; Janata, Petr

    2014-08-01

    Music often evokes spontaneous movements in listeners that are synchronized with the music, a phenomenon that has been characterized as being in "the groove." However, the musical factors that contribute to listeners' initiation of stimulus-coupled action remain unclear. Evidence suggests that newly appearing objects in auditory scenes orient listeners' attention, and that in multipart music, newly appearing instrument or voice parts can engage listeners' attention and elicit arousal. We posit that attentional engagement with music can influence listeners' spontaneous stimulus-coupled movement. Here, 2 experiments-involving participants with and without musical training-tested the effect of staggering instrument entrances across time and varying the number of concurrent instrument parts within novel multipart music on listeners' engagement with the music, as assessed by spontaneous sensorimotor behavior and self-reports. Experiment 1 assessed listeners' moment-to-moment ratings of perceived groove, and Experiment 2 examined their spontaneous tapping and head movements. We found that, for both musically trained and untrained participants, music with more instruments led to higher ratings of perceived groove, and that music with staggered instrument entrances elicited both increased sensorimotor coupling and increased reports of perceived groove. Although untrained participants were more likely to rate music as higher in groove, trained participants showed greater propensity for tapping along, and they did so more accurately. The quality of synchronization of head movements with the music, however, did not differ as a function of training. Our results shed new light on the relationship between complex musical scenes, attention, and spontaneous sensorimotor behavior.

  15. Macromolecular crowding: chemistry and physics meet biology (Ascona, Switzerland, 10-14 June 2012).

    Science.gov (United States)

    Foffi, G; Pastore, A; Piazza, F; Temussi, P A

    2013-08-02

    More than 60 years of biochemical and biophysical studies have accustomed us to think of proteins as highly purified entities that act in isolation, more or less freely diffusing until they find their cognate partner to bind to. While in vitro experiments that reproduce these conditions largely remain the only way to investigate the intrinsic properties of molecules, this approach ignores an important factor: in their natural milieu , proteins are surrounded by several other molecules of different chemical nature, and this crowded environment can considerably modify their behaviour. About 40% of the cellular volume on average is occupied by all sorts of molecules. Furthermore, biological macromolecules live and operate in an extremely structured and complex environment within the cell (endoplasmic reticulum, Golgi apparatus, cytoskeletal structures, etc). Hence, to further complicate the picture, the interior of the cell is by no means a simply crowded medium, rather, a most crowded and confining one. In recent times, several approaches have been developed in the attempt to take into account important factors such as the ones mentioned above, at both theoretical and experimental levels, so that this field of research is now emerging as one of the most thriving in molecular and cell biology (see figure 1). [Formula: see text] Figure 1. Left: number of articles containing the word 'crowding' as a keyword limited to the biological and chemical science domains (source: ISI Web of Science). The arrow flags the 2003 'EMBO Workshop on Biological Implications of Macromolecular Crowding' (Embo, 2012). Right: number of citations to articles containing the word 'crowding' limited to the same domains (bars) and an exponential regression curve (source: Elsevier Scopus). To promote the importance of molecular crowding and confinement and provide researchers active in this field an interdisciplinary forum for meeting and exchanging ideas, we recently organized an international

  16. Macromolecular crowding: chemistry and physics meet biology (Ascona, Switzerland, 10-14 June 2012)

    Science.gov (United States)

    Foffi, G.; Pastore, A.; Piazza, F.; Temussi, P. A.

    2013-08-01

    More than 60 years of biochemical and biophysical studies have accustomed us to think of proteins as highly purified entities that act in isolation, more or less freely diffusing until they find their cognate partner to bind to. While in vitro experiments that reproduce these conditions largely remain the only way to investigate the intrinsic properties of molecules, this approach ignores an important factor: in their natural milieu , proteins are surrounded by several other molecules of different chemical nature, and this crowded environment can considerably modify their behaviour. About 40% of the cellular volume on average is occupied by all sorts of molecules. Furthermore, biological macromolecules live and operate in an extremely structured and complex environment within the cell (endoplasmic reticulum, Golgi apparatus, cytoskeletal structures, etc). Hence, to further complicate the picture, the interior of the cell is by no means a simply crowded medium, rather, a most crowded and confining one. In recent times, several approaches have been developed in the attempt to take into account important factors such as the ones mentioned above, at both theoretical and experimental levels, so that this field of research is now emerging as one of the most thriving in molecular and cell biology (see figure 1). Figure 1. Figure 1. Left: number of articles containing the word 'crowding' as a keyword limited to the biological and chemical science domains (source: ISI Web of Science). The arrow flags the 2003 'EMBO Workshop on Biological Implications of Macromolecular Crowding' (Embo, 2012). Right: number of citations to articles containing the word 'crowding' limited to the same domains (bars) and an exponential regression curve (source: Elsevier Scopus). To promote the importance of molecular crowding and confinement and provide researchers active in this field an interdisciplinary forum for meeting and exchanging ideas, we recently organized an international conference

  17. Socioeconomic position and the risk of spontaneous abortion

    DEFF Research Database (Denmark)

    Norsker, Filippa Nyboe; Espenhain, Laura; rogvi, Sofie

    2012-01-01

    To investigate the relationship between different indicators of socioeconomic position and the risk of spontaneous abortion.......To investigate the relationship between different indicators of socioeconomic position and the risk of spontaneous abortion....

  18. Characterization of Multiple Light Damage Paradigms Reveals Regional Differences in Photoreceptor Loss

    OpenAIRE

    Thomas, Jennifer L.; Nelson, Craig M.; Luo, Xixia; Hyde, David R.; Thummel, Ryan

    2012-01-01

    Zebrafish provide an attractive model to study the retinal response to photoreceptor apoptosis due to its remarkable ability to spontaneously regenerate retinal neurons following damage. There are currently two widely used light-induced retinal degeneration models to damage photoreceptors in the adult zebrafish. One model uses constant bright light, whereas the other uses a short exposure to extremely intense ultraviolet light. Although both models are currently used, it is unclear whether th...

  19. [Bacterial vaginosis and spontaneous preterm birth].

    Science.gov (United States)

    Brabant, G

    2016-12-01

    To determine if bacterial vaginosis is a marker for risk of spontaneous preterm delivery and if its detection and treatment can reduce this risk. Consultation of the database Pubmed/Medline, Science Direct, and international guidelines of medical societies. Bacterial vaginosis (BV) is a dysbiosis resulting in an imbalance in the vaginal flora through the multiplication of anaerobic bacteria and jointly of a disappearance of well-known protective Lactobacilli. His diagnosis is based on clinical Amsel criteria and/or a Gram stain with establishment of the Nugent score. The prevalence of the BV extraordinarily varies according to ethnic and/or geographical origin (4-58 %), in France, it is close to 7 % in the first trimester of pregnancy (EL2). The link between BV and spontaneous premature delivery is low with an odds ratio between 1.5 and 2 in the most recent studies (EL3). Metronidazole or clindamycin is effective to treat BV (EL3). It is recommended to prescribe one of these antibiotics in the case of symptomatic BV (Professional Consensus). The testing associated with the treatment of BV in the global population showed no benefit in the prevention of the risk of spontaneous preterm delivery (EL2). Concerning low-risk asymptomatic population (defined by the absence of antecedent of premature delivery), it has been failed profit to track and treat the BV in the prevention of the risk of spontaneous preterm delivery (EL1). Concerning the high-risk population (defined by a history of preterm delivery), it has been failed profit to track and treat the VB in the prevention of the risk of spontaneous preterm delivery (EL3). However, in the sub population of patients with a history of preterm delivery occurred in a context of materno-fetal bacterial infection, there may be a benefit to detect and treat early and systematically genital infection, and in particular the BV (Professional Consensus). The screening and treatment of BV during pregnancy in asymptomatic low

  20. Diabetes and nerve damage

    Science.gov (United States)

    Diabetic neuropathy; Diabetes - neuropathy; Diabetes - peripheral neuropathy ... In people with diabetes, the body's nerves can be damaged by decreased blood flow and a high blood sugar level. This condition is ...

  1. Continuous damage mechanics

    International Nuclear Information System (INIS)

    Chaboche, J.L.

    1981-01-01

    The classical structural life predictions are based on stabilized stress-strain analysis and some parametric relations with the number of cycles to failure. During the last ten years a different approach, initiated by the works of Kachanov and Rabotnov for creep rupture, has been developed by different laboratories. This continuous Damage Mechanics, treating the damaged material as a macroscopically homogeneous one, leads to the possibility of globally modelling the nucleation and the propagation of microdefects including their effect on the stress-strain behaviour. This paper presents the general theory and several applications to a turbine blade refractory alloy. It includes the description of sequence effects and creep-fatigue interaction. The generalization for three-dimensional conditions, where anisotropic damage effects are possible, is discussed and some new proposals are given for the determination of simple anisotropic damage equations. (orig.)

  2. LSD and Genetic Damage

    Science.gov (United States)

    Dishotsky, Norman I.; And Others

    1971-01-01

    Reviews studies of the effects of lysergic acid diethylamide (LSD) on man and other organisms. Concludes that pure LSD injected in moderate doses does not cause chromosome or detectable genetic damage and is not a teratogen or carcinogen. (JM)

  3. The effect of macromolecular crowding on mobility of biomolecules, association kinetics and gene expression in living cells

    Science.gov (United States)

    Tabaka, Marcin; Kalwarczyk, Tomasz; Szymanski, Jedrzej; Hou, Sen; Hołyst, Robert

    2014-09-01

    We discuss a quantitative influence of macromolecular crowding on biological processes: motion, bimolecular reactions, and gene expression in prokaryotic and eukaryotic cells. We present scaling laws relating diffusion coefficient of an object moving in a cytoplasm of cells to a size of this object and degree of crowding. Such description leads to the notion of the length scale dependent viscosity characteristic for all living cells. We present an application of the length-scale dependent viscosity model to the description of motion in the cytoplasm of both eukaryotic and prokaryotic living cells. We compare the model with all recent data on diffusion of nanoscopic objects in HeLa, and E. coli cells. Additionally a description of the mobility of molecules in cell nucleus is presented. Finally we discuss the influence of crowding on the bimolecular association rates and gene expression in living cells.

  4. A new on-axis multimode spectrometer for the macromolecular crystallography beamlines of the Swiss Light Source

    International Nuclear Information System (INIS)

    Owen, Robin L.; Pearson, Arwen R.; Meents, Alke; Boehler, Pirmin; Thominet, Vincent; Schulze-Briese, Clemens

    2009-01-01

    Complementary techniques greatly aid the interpretation of macromolecule structures to yield functional information, and can also help to track radiation-induced changes. A new on-axis spectrometer being integrated into the macromolecular crystallography beamlines of the Swiss Light Source is presented. X-ray crystallography at third-generation synchrotron sources permits tremendous insight into the three-dimensional structure of macromolecules. Additional information is, however, often required to aid the transition from structure to function. In situ spectroscopic methods such as UV–Vis absorption and (resonance) Raman can provide this, and can also provide a means of detecting X-ray-induced changes. Here, preliminary results are introduced from an on-axis UV–Vis absorption and Raman multimode spectrometer currently being integrated into the beamline environment at X10SA of the Swiss Light Source. The continuing development of the spectrometer is also outlined

  5. Recent Advances in the Analysis of Macromolecular Interactions Using the Matrix-Free Method of Sedimentation in the Analytical Ultracentrifuge

    Directory of Open Access Journals (Sweden)

    Stephen E. Harding

    2015-03-01

    Full Text Available Sedimentation in the analytical ultracentrifuge is a matrix free solution technique with no immobilisation, columns, or membranes required and can be used to study self-association and complex or “hetero”-interactions, stoichiometry, reversibility and interaction strength of a wide variety of macromolecular types and across a very large dynamic range (dissociation constants from 10−12 M to 10−1 M. We extend an earlier review specifically highlighting advances in sedimentation velocity and sedimentation equilibrium in the analytical ultracentrifuge applied to protein interactions and mucoadhesion and to review recent applications in protein self-association (tetanus toxoid, agrin, protein-like carbohydrate association (aminocelluloses, carbohydrate-protein interactions (polysaccharide-gliadin, nucleic-acid protein (G-duplexes, nucleic acid-carbohydrate (DNA-chitosan and finally carbohydrate-carbohydrate (xanthan-chitosan and a ternary polysaccharide complex interactions.

  6. A fast band–Krylov eigensolver for macromolecular functional motion simulation on multicore architectures and graphics processors

    Energy Technology Data Exchange (ETDEWEB)

    Aliaga, José I., E-mail: aliaga@uji.es [Depto. Ingeniería y Ciencia de Computadores, Universitat Jaume I, Castellón (Spain); Alonso, Pedro [Departamento de Sistemas Informáticos y Computación, Universitat Politècnica de València (Spain); Badía, José M. [Depto. Ingeniería y Ciencia de Computadores, Universitat Jaume I, Castellón (Spain); Chacón, Pablo [Dept. Biological Chemical Physics, Rocasolano Physics and Chemistry Institute, CSIC, Madrid (Spain); Davidović, Davor [Rudjer Bošković Institute, Centar za Informatiku i Računarstvo – CIR, Zagreb (Croatia); López-Blanco, José R. [Dept. Biological Chemical Physics, Rocasolano Physics and Chemistry Institute, CSIC, Madrid (Spain); Quintana-Ortí, Enrique S. [Depto. Ingeniería y Ciencia de Computadores, Universitat Jaume I, Castellón (Spain)

    2016-03-15

    We introduce a new iterative Krylov subspace-based eigensolver for the simulation of macromolecular motions on desktop multithreaded platforms equipped with multicore processors and, possibly, a graphics accelerator (GPU). The method consists of two stages, with the original problem first reduced into a simpler band-structured form by means of a high-performance compute-intensive procedure. This is followed by a memory-intensive but low-cost Krylov iteration, which is off-loaded to be computed on the GPU by means of an efficient data-parallel kernel. The experimental results reveal the performance of the new eigensolver. Concretely, when applied to the simulation of macromolecules with a few thousands degrees of freedom and the number of eigenpairs to be computed is small to moderate, the new solver outperforms other methods implemented as part of high-performance numerical linear algebra packages for multithreaded architectures.

  7. Sample preparation of biological macromolecular assemblies for the determination of high-resolution structures by cryo-electron microscopy.

    Science.gov (United States)

    Stark, Holger; Chari, Ashwin

    2016-02-01

    Single particle cryo-EM has recently developed into a powerful tool to determine the 3D structure of macromolecular complexes at near-atomic resolution, which allows structural biologists to build atomic models of proteins. All technical aspects of cryo-EM technology have been considerably improved over the last two decades, including electron microscopic hardware, image processing software and the ever growing speed of computers. This leads to a more widespread use of the technique, and it can be anticipated that further automation of electron microscopes and image processing tools will soon fully shift the focus away from the technological aspects, onto biological questions that can be answered. In single particle cryo-EM, no crystals of a macromolecule are required. In contrast to X-ray crystallography, this significantly facilitates structure determination by cryo-EM. Nevertheless, a relatively high level of biochemical control is still essential to obtain high-resolution structures by cryo-EM, and it can be anticipated that the success of the cryo-EM technology goes hand in hand with further developments of sample purification and preparation techniques. This will allow routine high-resolution structure determination of the many macromolecular complexes of the cell that until now represent evasive targets for X-ray crystallographers. Here we discuss the various biochemical tools that are currently available and the existing sample purification and preparation techniques for cryo-EM grid preparation that are needed to obtain high-resolution images for structure determination. © The Author 2015. Published by Oxford University Press on behalf of The Japanese Society of Microscopy. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  8. Single-step antibody-based affinity cryo-electron microscopy for imaging and structural analysis of macromolecular assemblies.

    Science.gov (United States)

    Yu, Guimei; Vago, Frank; Zhang, Dongsheng; Snyder, Jonathan E; Yan, Rui; Zhang, Ci; Benjamin, Christopher; Jiang, Xi; Kuhn, Richard J; Serwer, Philip; Thompson, David H; Jiang, Wen

    2014-07-01

    Single particle cryo-electron microscopy (cryo-EM) is an emerging powerful tool for structural studies of macromolecular assemblies (i.e., protein complexes and viruses). Although single particle cryo-EM requires less concentrated and smaller amounts of samples than X-ray crystallography, it remains challenging to study specimens that are low-abundance, low-yield, or short-lived. The recent development of affinity grid techniques can potentially further extend single particle cryo-EM to these challenging samples by combining sample purification and cryo-EM grid preparation into a single step. Here we report a new design of affinity cryo-EM approach, cryo-SPIEM, that applies a traditional pathogen diagnosis tool Solid Phase Immune Electron Microscopy (SPIEM) to the single particle cryo-EM method. This approach provides an alternative, largely simplified and easier to use affinity grid that directly works with most native macromolecular complexes with established antibodies, and enables cryo-EM studies of native samples directly from cell cultures. In the present work, we extensively tested the feasibility of cryo-SPIEM with multiple samples including those of high or low molecular weight, macromolecules with low or high symmetry, His-tagged or native particles, and high- or low-yield macromolecules. Results for all these samples (non-purified His-tagged bacteriophage T7, His-tagged Escherichiacoli ribosomes, native Sindbis virus, and purified but low-concentration native Tulane virus) demonstrated the capability of cryo-SPIEM approach in specifically trapping and concentrating target particles on TEM grids with minimal view constraints for cryo-EM imaging and determination of 3D structures. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. Macromolecular composition of phloem exudate from white lupin (Lupinus albus L.

    Directory of Open Access Journals (Sweden)

    Mann Anthea J

    2011-02-01

    Full Text Available Abstract Background Members of the legume genus Lupinus exude phloem 'spontaneously' from incisions made to the vasculature. This feature was exploited to document macromolecules present in exudate of white lupin (Lupinus albus [L.] cv Kiev mutant, in particular to identify proteins and RNA molecules, including microRNA (miRNA. Results Proteomic analysis tentatively identified 86 proteins from 130 spots collected from 2D gels analysed by partial amino acid sequence determination using MS/MS. Analysis of a cDNA library constructed from exudate identified 609 unique transcripts. Both proteins and transcripts were classified into functional groups. The largest group of proteins comprised those involved in metabolism (24%, followed by protein modification/turnover (9%, redox regulation (8%, cell structural components (6%, stress and defence response (6% with fewer in other groups. More prominent proteins were cyclophilin, ubiquitin, a glycine-rich RNA-binding protein, a group of proteins that comprise a glutathione/ascorbate-based mechanism to scavenge oxygen radicals, enzymes of glycolysis and other metabolism including methionine and ethylene synthesis. Potential signalling macromolecules such as transcripts encoding proteins mediating calcium level and the Flowering locus T (FT protein were also identified. From around 330 small RNA clones (18-25 nt 12 were identified as probable miRNAs by homology with those from other species. miRNA composition of exudate varied with site of collection (e.g. upward versus downward translocation streams and nutrition (e.g. phosphorus level. Conclusions This is the first inventory of macromolecule composition of phloem exudate from a species in the Fabaceae, providing a basis to identify systemic signalling macromolecules with potential roles in regulating development, growth and stress response of legumes.

  10. F. VON HAYEK’S THEORY OF SPONTANEOUS ORDER

    Directory of Open Access Journals (Sweden)

    О. Nesterenko

    2013-04-01

    Full Text Available The essence and the genesis of spontaneous order are disclosed in the context of critical analysis of constructivism. The author’s approach to the definition of the characteristic features of the spontaneous order is proposed. The dichotomy of the order is revealed towards the economic sphere in form of spontaneous order and organization.

  11. Macromolecular Engineering: New Routes Towards the Synthesis of Well-??Defined Polyethers/Polyesters Co/Terpolymers with Different Architectures

    KAUST Repository

    Alamri, Haleema

    2016-05-18

    The primary objective of this research was to develop a new and efficient pathway for well-defined multicomponent homo/co/terpolymers of cyclic esters/ethers using an organocatalytic approach with an emphasis on the macromolecular engineering aspects of the overall synthesis. Macromolecular engineering (as discussed in the first chapter) of homo/copolymers refers to the specific tailoring of these materials for achieving an easy and reproducible synthesis that results in precise molecular characteristics, i.e. molecular weight and polydispersity, as well as specific structure and end?group choices. Precise control of these molecular characteristics will provide access to new materials that can be used for pre-targeted purposes such as biomedical applications. Among the most commonly used engineering materials are polyesters (biocompatible and biodegradable) and polyethers (biocompatible), either as homopolymers or when or copolymers with linear structures. The ability to create non-linear structures, for example stars, will open new horizons in the applications of these important polymeric materials. The second part of this thesis describes the synthesis of aliphatic polyesters, particularly polycaprolactone and polylactide, using a metal-free initiator/catalyst system. A phosphazene base (t?BuP2) was used as the catalyst for the ring-opening copolymerization of ?-aprolactone (??CL) and L,Lactide (LLA) at room temperature with a variety of protic initiators in different solvents. These studies provided important information for the design of a metal-free route toward the synthesis of polyester?based (bio) materials. The third part of the thesis describes a novel route for the one?pot synthesis of polyether-b polyester block copolymers with either a linear or a specific macromolecular architecture. Poly (styrene oxide)?b?poly(caprolactone)?b?poly(L,lactide) was prepared using this method with the goal of synthesizing poly(styrene oxide)-based materials since this

  12. The high frequency of spontaneous micronuclei observed in lymphocytes of systemic sclerosis patients: preliminary results

    Directory of Open Access Journals (Sweden)

    L. Migliore

    2011-09-01

    Full Text Available Objective: aim of the study is to assess the presence of spontaneous chromosome damage in patients affected by limited (lSSc or diffuse (dSSc Systemic Slerosis, using the micronucleus (MN assay. Methods: we evaluated MN frequency in cultured peripheral lymphocytes of 18 SSc and in a group of 20 healthy controls. Patients were also classified as ACA+, Scl70+, FAN+ according to the presence of the specific anti-nuclear antibodies. We also explored the hypothesis that the extent of cytogenetic alteration might be related to the severity of the pathological condition and/or to the immunological profile. Results: compared to controls, the patient group as a whole showed significantly higher MN frequencies (10.8±4.5 vs. 27.8±13.7, p<0.001. No correlation was found between spontaneous chromosome damage and severity of the disease, being MN frequency 33.1±17.0 and 19.8±2.7 in lSSc and dSSc, respectively. Interestingly, ACA+ subjects displayed the highest MN frequency (36.9±15.0, as compared to patients with different antibody pattern (Scl70+, FAN+; 19.7±8.2. Conclusions: our results confirm the presence of chromosomal damage in circulating lymphocytes of SSc patients and would suggest a key role of antibodies to the centromere in determining the observed cytogenetic anomalies.

  13. [Spontaneous renal artery dissection: a case report].

    Science.gov (United States)

    Maehana, Takeshi; Nishida, Sachiyo; Shindo, Tetsuya; Miyamoto, Shintaro; Muranaka, Takashi; Suzuki, Kazuhiro; Yanase, Masahiro

    2008-01-01

    A 65-year-old female was admitted to our hospital complaining of left upper abdominal pain. Although the symptom improved with observation, serum creatinine rose to 2.0 mg/dl. Slight atrophy of the left kidney was seen on abdominal plain computed tomography. In order to examine the possibility of renal infarction from thrombosis with angiography, we consulted the department of cardiovascular medicine. Even though we did not detect thrombosis with left renal angiography or intravascular ultrasound, there was a dissection finding localized at the left renal artery. Based on this finding, we made a diagnosis of spontaneous renal artery dissection and performed stent placement. Spontaneous renal artery dissection is extremely rare and the frequency of occurrence is reported to be less than 0.05%. Recently, however the frequency of detection has risen with the development of clinical imaging. We must keep in mind that the condition has the possibility of leading to renal blood circulation disorders.

  14. Thermal influences on spontaneous rock dome exfoliation

    Science.gov (United States)

    Collins, Brian D.; Stock, Greg M.; Eppes, Martha C.; Lewis, Scott W.; Corbett, Skye C.; Smith, Joel B.

    2018-01-01

    Rock domes, with their onion-skin layers of exfoliation sheets, are among the most captivating landforms on Earth. Long recognized as integral in shaping domes, the exact mechanism(s) by which exfoliation occurs remains enigmatic, mainly due to the lack of direct observations of natural events. In August 2014, during the hottest days of summer, a granitic dome in California, USA, spontaneously exfoliated; witnesses observed extensive cracking, including a ~8000 kg sheet popping into the air. Subsequent exfoliation episodes during the following two summers were recorded by instrumentation that captured—for the first time—exfoliation deformation and stress conditions. Here we show that thermal cycling and cumulative dome surface heating can induce subcritical cracking that culminates in seemingly spontaneous exfoliation. Our results indicate that thermal stresses—largely discounted in dome formation literature—can play a key role in triggering exfoliation and therefore may be an important control for shaping domes worldwide.

  15. Spontaneous abortion and physical strain around implantation

    DEFF Research Database (Denmark)

    Hjøllund, Niels Henrik Ingvar; Jensen, T.K.; Bonde, J.P.

    2000-01-01

    Existing studies of physical strain and spontaneous abortion are mainly retrospective or based only on pregnancies that have survived the first trimester. Furthermore, almost all studies have relied on averaged measures of physical strain, which tend to blur an effect if peak values during short...... time periods are the relevant measure. We followed a cohort of first pregnancy planners from termination of birth control until pregnancy for a maximum of six menstrual cycles. The analyses include 181 pregnancies, of which 32 were subclinical pregnancies detected by hCG analysis only. During early...... pregnancy the women recorded physical strain prospectively in a structured diary. Physical strain around the time of implantation was associated with later spontaneous abortion. The adjusted risk ratio for women who reported physical strain higher than average at day 6 to 9 after the estimated date...

  16. Spontaneous Enterocutaneous Fistula Resulting from Richter's Hernia.

    Science.gov (United States)

    Hajong, Ranendra; Khongwar, Donkupar; Komut, Ojing; Naku, Narang; Baru, Kappa

    2017-08-01

    Richter's hernia is due to the entrapment of a part of circumference of the bowel wall. As the bowel continuity is maintained, the patients usually do not have intestinal obstruction. Some patients with Richter's hernia may present with enterocutaneous fistula either spontaneous or due to surgical intervention mistaking the obstructed hernia to be inguinal abscess. This is more so in developing countries due to lack of awareness among the masses or due to the delay in seeking medical attention. Presenting here is a case of a 53-year-old male patient with enterocutaneous fistula which occurred spontaneously and sought medical attention only after about three years of repeated discharge of yellowish fluid from the left inguinal region. Magnetic resonance fistulogram confirmed the diagnosis of enterocutaneous fistula. Laparotomy with resection and primary anastomosis of the fistulous bowel was done. Patient recovered uneventfully without any complications or recurrence.

  17. Spontaneous Coronary Artery Dissection and Pregnancy.

    Science.gov (United States)

    Naderi, Sahar

    2017-09-01

    Spontaneous coronary artery dissection (SCAD) is a non-atherosclerotic, non-traumatic cause of coronary artery dissection. SCAD is the most common cause of myocardial infarction in pregnancy or the postpartum period and results in significant cardiovascular morbidity and mortality in the pregnant population. It is important to consider pregnancy-associated spontaneous coronary artery dissection (PASCAD) high on the differential for a pregnant woman who presents with symptoms consistent with acute coronary syndrome. Management of these patients requires a thoughtful, multidisciplinary approach, with consideration of conservative management if possible. Counseling regarding future pregnancies is also critical and requires compassionate care. Given our limited understanding of SCAD, including PASCAD, more data and research are needed to help guide diagnosis, management, and determination of prognosis.

  18. Spontaneous stress fractures of the femoral neck

    International Nuclear Information System (INIS)

    Dorne, H.L.; Lander, P.H.

    1985-01-01

    The diagnosis of spontaneous stress fractures of the femoral neck, a form of insufficiency stress fracture, can be missed easily. Patients present with unremitting hip pain without a history of significant trauma or unusual increase in daily activity. The initial radiographic features include osteoporosis, minor alterations of trabecular alignment, minimal extracortical or endosteal reaction, and lucent fracture lines. Initial scintigraphic examinations performed in three of four patients showed focal increased radionuclide uptake in two and no focal abnormality in one. Emphasis is placed on the paucity of early findings. Evaluation of patients with persistent hip pain requires a high degree of clinical suspicion and close follow-up; the sequelae of undetected spontaneous fractures are subcapital fracture with displacement, angular deformity, and a vascular necrosis of the femoral head

  19. Motivational Projections of Russian Spontaneous Speech

    Directory of Open Access Journals (Sweden)

    Galina M. Shipitsina

    2017-06-01

    Full Text Available The article deals with the semantic, pragmatic and structural features of words, phrases, dialogues motivation, in the contemporary Russian popular speech. These structural features are characterized by originality and unconventional use. Language material is the result of authors` direct observation of spontaneous verbal communication between people of different social and age groups. The words and remarks were analyzed in compliance with the communication system of national Russian language and cultural background of popular speech. Studies have discovered that in spoken discourse there are some other ways to increase the expression statement. It is important to note that spontaneous speech identifies lacunae in the nominative language and its vocabulary system. It is proved, prefixation is also effective and regular way of the same action presenting. The most typical forms, ways and means to update language resources as a result of the linguistic creativity of native speakers were identified.

  20. Processing of free radical damaged DNA bases

    International Nuclear Information System (INIS)

    Wallace, S.

    2003-01-01

    Free radicals produced during the radiolysis of water gives rise to a plethora of DNA damages including single strand breaks, sites of base loss and a wide variety of purine and pyrimidine base lesions. All these damages are processed in cells by base excision repair. The oxidative DNA glycosylases which catalyze the first step in the removal of a base damage during base excision repair evolved primarily to protect the cells from the deleterious mutagenic effects of single free radical-induced DNA lesions arising during oxidative metabolism. This is evidenced by the high spontaneous mutation rate in bacterial mutants lacking the oxidative DNA glycosylases. However, when a low LET photon transverses the DNA molecule, a burst of free radicals is produced during the radiolysis of water that leads to the formation of clustered damages in the DNA molecule, that are recognized by the oxidative DNA glycosylases. When substrates containing two closely opposed sugar damages or base and sugar damages are incubated with the oxidative DNA glycosylases in vitro, one strand is readily incised by the lyase activity of the DNA glycosylase. Whether or not the second strand is incised depends on the distance between the strand break resulting from the incised first strand and the remaining DNA lesion on the other strand. If the lesions are more than two or three base pairs apart, the second strand is readily cleaved by the DNA glycosylase, giving rise to a double strand break. Even if the entire base excision repair system is reconstituted in vitro, whether or not a double strand break ensues depends solely upon the ability of the DNA glycosylase to cleave the second strand. These data predicted that cells deficient in the oxidative DNA glycosylases would be radioresistant while those that overproduce an oxidative DNA glycosylase would be radiosensitive. This prediction was indeed borne in Escherichia coli that is, mutants lacking the oxidative DNA glycosylases are radioresistant

  1. Spontaneous pneumomediastinum due to paralytic rabies

    Directory of Open Access Journals (Sweden)

    Wuping Wang

    2013-02-01

    Full Text Available Rabies is a fatal disease resulting from rabies virus infection, causing severe neurological symptoms and ultimately death by destroying the nervous system. In general, a patient tends to see a neurologist or an infectious diseases physician, with very common and typical discipline-related signs and symptoms, such as hydrophobia, aerophobia, and mental disorders. However, we reported a rabies patient who was first admitted to see a thoracic surgeon with spontaneous pneumomediastinum.

  2. Spontaneous pneumomediastinum due to paralytic rabies

    Directory of Open Access Journals (Sweden)

    Wuping Wang

    Full Text Available Rabies is a fatal disease resulting from rabies virus infection, causing severe neurological symptoms and ultimately death by destroying the nervous system. In general, a patient tends to see a neurologist or an infectious diseases physician, with very common and typical discipline-related signs and symptoms, such as hydrophobia, aerophobia, and mental disorders. However, we reported a rabies patient who was first admitted to see a thoracic surgeon with spontaneous pneumomediastinum.

  3. Self energy QED: Multipole spontaneous emission

    International Nuclear Information System (INIS)

    Salamin, Y.I.

    1990-08-01

    Within the context of Barut's self-field approach, we write the exact expression of the spontaneous atomic decay rate (Phys. Rev. A37, 2284 (1988)), in the long wavelength approximation, in terms of electric- and magnetic-like multipole contributions which are related to the matrix elements of the transition charge and current distributions of the relativistic electron. A number of features of these expressions are discussed and their generalization to interacting composite systems is also pointed out. (author). 8 refs

  4. Quantum mechanics with spontaneous localization and experiments

    International Nuclear Information System (INIS)

    Benatti, F.; Grassi, R.

    1994-05-01

    We examine from an experimental point of view the recently proposed models of spontaneous reduction. We compare their implications about decoherence with those of environmental effects. We discuss the treatment, within the considered models, of the so called quantum telegraph phenomenon and we show that, contrary to what has been recently stated, no problems are met. Finally, we review recent interesting work investigating the implications of dynamical reduction for the proton decay. (author). 16 refs, 4 figs, 3 tabs

  5. Spontaneous atlantoaxial subluxation associated with tonsillitis

    OpenAIRE

    Shunmugam, Meenalochani; Poonnoose, Santosh

    2015-01-01

    Atlantoaxial subluxation is a rare condition and requires a high index of suspicion to diagnose and treat in order to avoid long-term sequelae. Here, we present a case of late presentation of a nontraumatic rotatory subluxation of the atlantoaxial joint or atlantoaxial rotatory subluxation. A 17-year-old girl presented 3 months after the onset of nonspecific upper limb sensory symptoms which eventually settled spontaneously. Initial conservative management by the general practitioner had no e...

  6. Spontaneous Regression of a Cervical Disk Herniation

    Directory of Open Access Journals (Sweden)

    Emre Delen

    2014-03-01

    Full Text Available A 54 years old female patient was admitted to our outpatient clinic with a two months history of muscle spasms of her neck and pain radiating to the left upper extremity. Magnetic resonance imaging had shown a large left-sided paracentral disk herniation at the C6-C7 disk space (Figure 1. Neurological examination showed no obvious neurological deficit. She received conservative treatment including bed rest, rehabilitation, and analgesic drugs. After 13 months, requested by the patient, a second magnetic resonance imaging study showed resolution of the disc herniation.(Figure 2 Although the literature contains several reports about spontaneous regression of herniated lumbar disc without surgical intervention, that of phenomenon reported for herniated cervical level is rare, and such reports are few[1]. In conclusion, herniated intervertebral disc have the potential to spontaneously regress independently from the spine level. With further studies, determining the predictive signs for prognostic evaluation for spontaneous regression which would yield to conservative treatment would be beneficial.

  7. Spontaneously emerging cortical representations of visual attributes

    Science.gov (United States)

    Kenet, Tal; Bibitchkov, Dmitri; Tsodyks, Misha; Grinvald, Amiram; Arieli, Amos

    2003-10-01

    Spontaneous cortical activity-ongoing activity in the absence of intentional sensory input-has been studied extensively, using methods ranging from EEG (electroencephalography), through voltage sensitive dye imaging, down to recordings from single neurons. Ongoing cortical activity has been shown to play a critical role in development, and must also be essential for processing sensory perception, because it modulates stimulus-evoked activity, and is correlated with behaviour. Yet its role in the processing of external information and its relationship to internal representations of sensory attributes remains unknown. Using voltage sensitive dye imaging, we previously established a close link between ongoing activity in the visual cortex of anaesthetized cats and the spontaneous firing of a single neuron. Here we report that such activity encompasses a set of dynamically switching cortical states, many of which correspond closely to orientation maps. When such an orientation state emerged spontaneously, it spanned several hypercolumns and was often followed by a state corresponding to a proximal orientation. We suggest that dynamically switching cortical states could represent the brain's internal context, and therefore reflect or influence memory, perception and behaviour.

  8. Spontaneous prediction error generation in schizophrenia.

    Directory of Open Access Journals (Sweden)

    Yuichi Yamashita

    Full Text Available Goal-directed human behavior is enabled by hierarchically-organized neural systems that process executive commands associated with higher brain areas in response to sensory and motor signals from lower brain areas. Psychiatric diseases and psychotic conditions are postulated to involve disturbances in these hierarchical network interactions, but the mechanism for how aberrant disease signals are generated in networks, and a systems-level framework linking disease signals to specific psychiatric symptoms remains undetermined. In this study, we show that neural networks containing schizophrenia-like deficits can spontaneously generate uncompensated error signals with properties that explain psychiatric disease symptoms, including fictive perception, altered sense of self, and unpredictable behavior. To distinguish dysfunction at the behavioral versus network level, we monitored the interactive behavior of a humanoid robot driven by the network. Mild perturbations in network connectivity resulted in the spontaneous appearance of uncompensated prediction errors and altered interactions within the network without external changes in behavior, correlating to the fictive sensations and agency experienced by episodic disease patients. In contrast, more severe deficits resulted in unstable network dynamics resulting in overt changes in behavior similar to those observed in chronic disease patients. These findings demonstrate that prediction error disequilibrium may represent an intrinsic property of schizophrenic brain networks reporting the severity and variability of disease symptoms. Moreover, these results support a systems-level model for psychiatric disease that features the spontaneous generation of maladaptive signals in hierarchical neural networks.

  9. Spontaneous Large Serous Retinal Pigment Epithelial Tear

    Directory of Open Access Journals (Sweden)

    Voraporn Chaikitmongkol

    2012-10-01

    Full Text Available Purpose: To report cases of spontaneous retinal pigment epithelial (RPE tear complicating serous pigment epithelial detachment (PED. Methods: The records of 3 Asian patients with spontaneous giant RPE tear were reviewed retrospectively by including clinical presentation, angiography, optical coherence tomography, fundus autofluorescence imaging, and visual outcome. Results: Three patients (4 eyes were included in this study, with a mean age of 48.3 (42–56 years, and a mean follow-up period of 7.75 (4–18 months. Fundus examination in all patients showed giant RPE tear associated with bullous PED. Two cases had a history of prior corticosteroid use, and 1 had no history of medication use. All 3 patients developed spontaneous resolution of subretinal fluid with no treatment. However, in patients who used corticosteroids, initial progression of the tear and subretinal fluid were observed despite ceasing medication. On subsequent follow-up, an incomplete RPE regeneration was demonstrated by fundus autofluorescence imaging, and choroidal neovascularization developed in 1 patient. Conclusion: Large PED with RPE tear is a rare manifestation. When the fovea is spared, visual prognosis is favorable. No specific treatment is required, but careful choroidal neovascularization monitoring should be performed.

  10. Spontaneous fission of the heaviest elements

    Energy Technology Data Exchange (ETDEWEB)

    Hoffman, D.C.

    1989-04-01

    Although spontaneous fission was discovered in /sup 238/U in 1940, detailed studies of the process were first made possible in the 1960's with the availability of milligram quantities of /sup 252/Cf. The advent of solid-state detectors made it possible to perform measurements of coincident fission fragments from even very short-lived spontaneous fission activities or those available in only very small quantities. Until 1971 it was believed that the main features of the mass and kinetic-energy distributions were essentially the same as those for thermal neutron-induced fission and that all low-energy fission proceeded via asymmetric mass division with total kinetic energies which could be derived by linear extrapolation from those of lighter elements. In 1971, measurements of /sup 257/Fm showed an increase in symmetric mass division with anomalously high TKE's. Subsequent experiments showed that in /sup 258/Fm and /sup 259/Fm, the most probable mass split was symmetric with very high total kinetic energy. Measurements for the heavier elements have shown symmetric mass distributions with both high and low total kinetic energies. Recent results for spontaneous fission properties of the heaviest elements are reviewed and compared with theory. 31 refs., 8 figs., 1 tab.

  11. Lack of indication of myocardial cell damage after myocardial ischaemia in patients with severe stable angina

    DEFF Research Database (Denmark)

    Hansen, Knud Nørregaard; Egstrup, K; Nielsen, J R

    1992-01-01

    To evaluate myocardial cell damage in relation to spontaneous and exercise-induced ischaemia, release of myoglobin, creatine kinase (CK) and its isoenzyme MB (CK-MB) into the serum was estimated in 10 patients with severe stable angina. All patients had a positive exercise test, significant steno...

  12. Spontaneous Coronary Artery Dissection Associated With Pregnancy.

    Science.gov (United States)

    Tweet, Marysia S; Hayes, Sharonne N; Codsi, Elisabeth; Gulati, Rajiv; Rose, Carl H; Best, Patricia J M

    2017-07-25

    Spontaneous coronary artery dissection (SCAD) is the most common cause of pregnancy-associated myocardial infarction and remains poorly characterized. This study sought to assess presentation, clinical factors, and outcomes of pregnancy-associated spontaneous coronary artery dissection (P-SCAD) compared with spontaneous coronary artery dissection not associated with pregnancy (NP-SCAD). A Mayo Clinic registry was established in 2010 to include comprehensive retrospective and prospective SCAD data. Records were reviewed to identify women who were pregnant or ≤12 weeks postpartum at time of SCAD. Complete records were available for 323 women; 54 women met criteria for P-SCAD (4 during pregnancy) and they were compared with 269 women with NP-SCAD. Most events occurred within the first month postpartum (35 of 50). Compared with NP-SCAD, P-SCAD patients more frequently presented with ST-segment elevation myocardial infarction (57% vs. 36%; p = 0.009), left main or multivessel SCAD (24% vs. 5%; p vs. 14%; p = 0.0027, respectively), and left ventricular function ≤35% (26% vs. 10%; p = 0.0071). Among women with imaging of other vascular territories, P-SCAD was less likely with a diagnosis of fibromuscular dysplasia and extracoronary vascular abnormalities (42% vs. 64%; p = 0.047; and 46% vs. 77%; p = 0.0032, respectively). Compared with U.S. birth data, women with P-SCAD were more often multiparous (p = 0.0167), had a history of infertility therapies (p = 0.0004), and had pre-eclampsia (p = 0.001). On long-term follow-up (median 2.3 years) recurrent SCAD occurred in 51 patients, with no difference in the Kaplan Meier 5-year recurrence rates (10% vs. 23%; p = 0.18). P-SCAD patients had more acute presentations and high-risk features than women with NP-SCAD did. The highest frequency of P-SCAD occurred during the first postpartum month and P-SCAD patients less often had extracoronary vascular abnormalities. Hormonal, hemodynamic variations, and yet

  13. Spontaneous Intracerebral Hemorrhage Image Analysis Methods: A Survey

    Science.gov (United States)

    Pérez, Noel; Valdés, Jose; Guevara, Miguel; Silva, Augusto

    Spontaneous intracerebral hemorrhages (ICH) account for 10-30% of all strokes and are a result of acute bleeding into the brain due to ruptures of small penetrating arteries. Despite major advancements in the management of ischemic strokes and other causes of hemorrhagic strokes, such as ruptured aneurysm, arteriovenous malformations (AVMs), or cavernous angioma, during the past several decades, limited progress has been made in the treatment of ICH, and the prognosis for patients who suffer them remains poor. The societal impact of these hemorrhagic strokes is magnified by the fact that affected patients typically are a decade younger than those afflicted with ischemic strokes. The ICH continues to kill or disable most of their victims. Some studies show that those who suffer ICH have a 30-day mortality rate of 35-44% and a 6-month mortality rate approaching 50%. Approximately 700,000 new strokes occur in the United States annually and approximately 15% are hem-orrhagic strokes related to ICH. The poor outcome associated with ICH is related to the extent of brain damage. ICH produces direct destruction and compression of surrounding brain tissue. Direct compression causes poor perfusion and venous drainage to surrounding penumbra at risk, resulting in ischemia to the tissues that most need perfusion [16].

  14. Spontaneous adrenal pheochromocytoma rupture complicated by intraperitoneal hemorrhage and shock

    Directory of Open Access Journals (Sweden)

    Kwasnik Edward

    2011-08-01

    Full Text Available Abstract MEN2A is a hereditary syndrome characterized by medullary thyroid carcinoma, hyperparathyroidism, and pheochromocytoma. Classically patients with a pheochromocytoma initially present with the triad of paroxysmal headaches, palpitations, and diaphoresis accompanied by marked hypertension. However, although reported as a rare presentation, spontaneous hemorrhage within a pheochromocytoma can present as an abdominal catastrophe. Unrecognized, this transformation can rapidly result in death. We report the only documented case of a thirty eight year old gentleman with MEN2A who presented to a community hospital with hemorrhagic shock and peritonitis secondary to an unrecognized hemorrhagic pheochromocytoma. The clinical course is notable for an inability to localize the source of hemorrhage during an initial damage control laparotomy that stabilized the patient sufficiently to allow emergent transfer to our facility, re-exploration for continued hemorrhage and abdominal compartment syndrome, and ultimately angiographic embolization of the left adrenal artery for control of the bleeding. Following recovery from his critical illness and appropriate medical management for pheochromocytoma, he returned for interval bilateral adrenal gland resection, from which his recovery was unremarkable. Our review of the literature highlights the high mortality associated with the undertaking of an operative intervention in the face of an unrecognized functional pheochromocytoma. This reinforces the need for maintaining a high index of suspicion for pheochromocytoma in similar cases. Our case also demonstrates the need for a mutimodal treatment approach that will often be required in these cases.

  15. Spontaneous Heterotopic Pregnancy: Dual Case Report and Review of Literature

    Directory of Open Access Journals (Sweden)

    Annika Chadee

    2016-01-01

    Full Text Available Introduction. Heterotopic pregnancy is a rare complication usually seen in populations at risk for ectopic pregnancy or those undergoing fertility treatments. It is a potentially dangerous condition occurring in only 1 in 30,000 spontaneous pregnancies. With the advent of Assisted Reproduction Techniques (ART and ovulation induction, the overall incidence of heterotopic pregnancy has risen to approximately 1 in 3,900 pregnancies. Other risk factors include a history of pelvic inflammatory disease (PID, tubal damage, pelvic surgery, uterine Mullerian abnormalities, and prior tubal surgery. Heterotopic pregnancy is a potentially fatal condition, rarely occurring in natural conception cycles. Most commonly, heterotopic pregnancy is diagnosed at the time of rupture when surgical management is required. Case. This paper represents two cases of heterotopic pregnancies as well as a literature review. Conclusion. Heterotopic pregnancy should be suspected in patients with an adnexal mass, even in the absence of risk factors. Clinicians must be alert to the fact that confirming an intrauterine pregnancy clinically or by ultrasound does not exclude the coexistence of an ectopic pregnancy. A high index of suspicion in women is needed for early and timely diagnosis, and management with laparotomy or laparoscopy can result in a favorable and successful obstetrical outcome.

  16. Spontaneous resolution of posterior ankle joint loose bodies after total ankle replacement: A case report.

    Science.gov (United States)

    Lee, Raymond P; Cheng, Sally H S

    2017-06-01

    Late stage ankle osteoarthritis often presents with debilitating pain. It is common to find osteophytes and loose body formation around the joint. Total ankle arthroplasty can preserve joint mobility and pain relieve for such patient. However, when trying to remove the osteophytes and loose bodies at the posterior ankle joint, there is risk of damaging posterior structures such as the neurovascular bundle during the procedure. We are presenting a case where the posterior loose bodies remained untouched during the operation, and patient showed spontaneous resolution of the lesions with time. Patient enjoyed good function outcome after the surgery. Copyright © 2016 European Foot and Ankle Society. Published by Elsevier Ltd. All rights reserved.

  17. Rosuvastatin ameliorates inflammation, renal fat accumulation, and kidney injury in transgenic spontaneously hypertensive rats expressing human C-reactive protein

    Czech Academy of Sciences Publication Activity Database

    Šilhavý, Jan; Zídek, Václav; Landa, Vladimír; Šimáková, Miroslava; Mlejnek, Petr; Oliyarnyk, O.; Malínská, H.; Kazdová, L.; Mancini, M.; Pravenec, Michal

    2015-01-01

    Roč. 64, č. 3 (2015), s. 295-301 ISSN 0862-8408 R&D Projects: GA MŠk(CZ) LH11049; GA MŠk(CZ) LL1204; GA MZd(CZ) NT14325; GA ČR(CZ) GB14-36804G Institutional support: RVO:67985823 Keywords : rosuvastatin * kidney damage * CRP * transgenic * spontaneously hypertensive rat Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.643, year: 2015

  18. Natural resource damage assessment

    International Nuclear Information System (INIS)

    Seddelmeyer, J.

    1991-01-01

    The assessment and collection of natural resource damages from petroleum and chemical companies unfortunate enough to have injured publicly owned natural resources is perhaps the most rapidly expanding area of environmental liability. The idea of recovering for injury to publicly owned natural resources is an extension of traditional common law tort concepts under which a person who negligently injures another or his property is called upon to compensate the injured party. Normally, once liability has been established, it is a fairly straightforward matter to calculate the various elements of loss, such as the cost to repair or replace damaged property, or medical expenses, and lost income. More difficult questions, such as the amount to be awarded for pain and suffering or emotional distress, are left to the jury, although courts limit the circumstances in which the jury is permitted to award such damages

  19. Coal transportation road damage

    International Nuclear Information System (INIS)

    Burtraw, D.; Harrison, K.; Pawlowski, J.A.

    1994-01-01

    Heavy trucks are primarily responsible for pavement damage to the nation's highways. In this paper we evaluate the pavement damage caused by coal trucks. We analyze the chief source of pavement damage (vehicle weight per axle, not total vehicle weight) and the chief cost involved (the periodic overlay that is required when a road's surface becomes worn). This analysis is presented in two stages. In the first section we present a synopsis of current economic theory including simple versions of the formulas that can be: used to calculate costs of pavement wear. In the second section we apply this theory to a specific example proximate to the reference environment for the Fuel Cycle Study in New Mexico in order to provide a numerical measure of the magnitude of the costs

  20. Spondias mombin L. (Anacardiaceae) enhances detoxification of hepatic and macromolecular oxidants in acetaminophen-intoxicated rats.

    Science.gov (United States)

    Saheed, Sabiu; Taofik, Sunmonu Olatunde; Oladipo, Ajani Emmanuel; Tom, Ashafa Anofi Omotayo

    2017-11-01

    Oxidative stress is a common pathological condition associated with drug-induced hepatotoxicity. This study investigated Spondias mombin L. aqueous leaf extract on reactive oxygen species and acetaminophen-mediated oxidative onslaught in rats' hepatocytes. Hepatotoxic rats were orally administered with the extract and vitamin C for 4 weeks. The extract dose-dependently scavenged DPPH, hydrogen peroxide and hydroxyl radicals, with IC 50 values of 0.13, 0.66, and 0.64 mg/mL, and corresponding % inhibitions of 89, 80, and 90%, respectively at 1.0 mg/mL. Ferric ion was also significantly reduced. The marked (p<0.05) increases in the activities of alkaline phosphatase, alanine aminotransferase and aspartate aminotransferase were reduced following treatment with the extract. The extract also significantly (p<0.05) induced the activities of antioxidant enzymes. These inductions reversed the acetaminophen-enhanced reduction in the specific activities of these enzymes as well as attenuated the observed elevated concentrations of autooxidized products and rived DNA in the acetaminophen-intoxicated animals. The observed effects competed with those of vitamin C and are suggestive of hepatoprotective and antioxidative attributes of the extract. Overall, the data from the present findings suggest that S. Mombin aqueous leaf extract is capable of ameliorating acetaminophen-mediated oxidative hepatic damage via enhancement of antioxidant defense systems.

  1. Radiation damage in single-particle cryo-electron microscopy: effects of dose and dose rate

    International Nuclear Information System (INIS)

    Karuppasamy, Manikandan; Karimi Nejadasl, Fatemeh; Vulovic, Milos; Koster, Abraham J.; Ravelli, Raimond B. G.

    2011-01-01

    The effects of dose and dose-rate were investigated for single-particle cryo-electron microscopy using stroboscopic data collection. A dose-rate effect was observed favoring lower flux densities. Radiation damage is an important resolution limiting factor both in macromolecular X-ray crystallography and cryo-electron microscopy. Systematic studies in macromolecular X-ray crystallography greatly benefited from the use of dose, expressed as energy deposited per mass unit, which is derived from parameters including incident flux, beam energy, beam size, sample composition and sample size. In here, the use of dose is reintroduced for electron microscopy, accounting for the electron energy, incident flux and measured sample thickness and composition. Knowledge of the amount of energy deposited allowed us to compare doses with experimental limits in macromolecular X-ray crystallography, to obtain an upper estimate of radical concentrations that build up in the vitreous sample, and to translate heat-transfer simulations carried out for macromolecular X-ray crystallography to cryo-electron microscopy. Stroboscopic exposure series of 50–250 images were collected for different incident flux densities and integration times from Lumbricus terrestris extracellular hemoglobin. The images within each series were computationally aligned and analyzed with similarity metrics such as Fourier ring correlation, Fourier ring phase residual and figure of merit. Prior to gas bubble formation, the images become linearly brighter with dose, at a rate of approximately 0.1% per 10 MGy. The gradual decomposition of a vitrified hemoglobin sample could be visualized at a series of doses up to 5500 MGy, by which dose the sample was sublimed. Comparison of equal-dose series collected with different incident flux densities showed a dose-rate effect favoring lower flux densities. Heat simulations predict that sample heating will only become an issue for very large dose rates (50 e − Å −2 s

  2. The In-Situ One-Step Synthesis of a PDC Macromolecular Pro-Drug and the Fabrication of a Novel Core-Shell Micell.

    Science.gov (United States)

    Yu, Cui-Yun; Yang, Sa; Li, Zhi-Ping; Huang, Can; Ning, Qian; Huang, Wen; Yang, Wen-Tong; He, Dongxiu; Sun, Lichun

    2016-01-01

    The development of slow release nano-sized carriers for efficient antineoplastic drug delivery with a biocompatible and biodegradable pectin-based macromolecular pro-drug for tumor therapy has been reported in this study. Pectin-doxorubicin conjugates (PDC), a macromolecular pro-drug, were prepared via an amide condensation reaction, and a novel amphiphilic core-shell micell based on a PDC macromolecular pro-drug (PDC-M) was self-assembled in situ, with pectin as the hydrophilic shell and doxorubicin (DOX) as the hydrophobic core. Then the chemical structure of the PDC macromolecular pro-drug was identified by both Fourier transform infrared spectroscopy (FTIR) and nuclear magnetic resonance spectroscopy ((1)H-NMR), and proved that doxorubicin combined well with the pectin and formed macromolecular pro-drug. The PDC-M were observed to have an unregularly spherical shape and were uniform in size by scanning electron microscopy (SEM). The average particle size of PDC-M, further measured by a Zetasizer nanoparticle analyzer (Nano ZS, Malvern Instruments), was about 140 nm. The encapsulation efficiency and drug loading were 57.82% ± 3.7% (n = 3) and 23.852% ±2.3% (n = 3), respectively. The in vitro drug release behaviors of the resulting PDC-M were studied in a simulated tumor environment (pH 5.0), blood (pH 7.4) and a lysosome media (pH 6.8), and showed a prolonged slow release profile. Assays for antiproliferative effects and flow cytometry of the resulting PDC-M in HepG2 cell lines demonstrated greater properties of delayed and slow release as compared to free DOX. A cell viability study against endothelial cells further revealed that the resulting PDC-M possesses excellent cell compatibilities and low cytotoxicities in comparison with that of the free DOX. Hemolysis activity was investigated in rabbits, and the results also demonstrated that the PDC-M has greater compatibility in comparison with free DOX. This shows that the resulting PDC-M can ameliorate the

  3. Multiple genetic switches spontaneously modulating bacterial mutability

    Directory of Open Access Journals (Sweden)

    Johnston Randal N

    2010-09-01

    Full Text Available Abstract Background All life forms need both high genetic stability to survive as species and a degree of mutability to evolve for adaptation, but little is known about how the organisms balance the two seemingly conflicting aspects of life: genetic stability and mutability. The DNA mismatch repair (MMR system is essential for maintaining genetic stability and defects in MMR lead to high mutability. Evolution is driven by genetic novelty, such as point mutation and lateral gene transfer, both of which require genetic mutability. However, normally a functional MMR system would strongly inhibit such genomic changes. Our previous work indicated that MMR gene allele conversion between functional and non-functional states through copy number changes of small tandem repeats could occur spontaneously via slipped-strand mis-pairing during DNA replication and therefore may play a role of genetic switches to modulate the bacterial mutability at the population level. The open question was: when the conversion from functional to defective MMR is prohibited, will bacteria still be able to evolve by accepting laterally transferred DNA or accumulating mutations? Results To prohibit allele conversion, we "locked" the MMR genes through nucleotide replacements. We then scored changes in bacterial mutability and found that Salmonella strains with MMR locked at the functional state had significantly decreased mutability. To determine the generalizability of this kind of mutability 'switching' among a wider range of bacteria, we examined the distribution of tandem repeats within MMR genes in over 100 bacterial species and found that multiple genetic switches might exist in these bacteria and may spontaneously modulate bacterial mutability during evolution. Conclusions MMR allele conversion through repeats-mediated slipped-strand mis-pairing may function as a spontaneous mechanism to switch between high genetic stability and mutability during bacterial evolution.

  4. Being Spontaneous: The Future of Telehealth Implementation?

    Science.gov (United States)

    Mars, Maurice; Scott, Richard E

    2017-09-01

    The smartphone simplifies interprofessional communication, and smartphone applications can facilitate telemedicine activity. Much has been written about the steps that need to be followed to implement and establish a successful telemedicine service that is integrated into everyday clinical practice. A traditional and systematic approach has evolved incorporating activities such as strategy development, needs assessment, business cases and plans, readiness assessment, implementation plans, change management interventions, and ongoing monitoring and evaluation. This "best practice" has been promoted in the telehealth literature for many years. In contrast, several recent initiatives have arisen without any such formal undertakings. This article describes the strengths and weaknesses of two "spontaneous" telemedicine services in dermatology and burn management that have evolved in South Africa. Two spontaneous services were identified and reviewed. In one unsolicited service, doctors at rural referring hospitals have been taking photographs of skin lesions and sending them with a brief text message history to dermatologists using the instant messaging smartphone app, WhatsApp. In the other, burns service, admissions to the burns unit or the clinic were triaged by telephonic description of the case and completion of a preadmission questionnaire. More recently, management and referral decisions are made only after completion of the questionnaire and subsequent submission of photographs of the burn sent by WhatsApp, with the decision transmitted by text message. Although efficient and effective, potential legal and ethical shortcomings have been identified. These "spontaneous" telehealth services challenge traditional best practice, yet appear to lead to truly integrated practice and, therefore, are successful and warrant further study.

  5. Core damage risk indicators

    International Nuclear Information System (INIS)

    Szikszai, T.

    1994-01-01

    The purpose of this document is to show a method for the fast recalculation of the PSA. To avoid the information loose, it is necessary to simplify the PSA models, or at least reorganize them. The method, introduced in this document, require that preparation, so we try to show, how to do that. This document is an introduction. This is the starting point of the work related to the development of the risk indicators. In the future, with the application of this method, we are going to show an everyday use of the PSA results to produce the indicators of the core damage risk. There are two different indicators of the plant safety performance, related to the core damage risk. The first is the core damage frequency indicator (CDFI), and the second is the core damage probability indicator (CDPI). Of course, we cannot describe all of the possible ways to use these indicators, rather we will try to introduce the requirements to establish such an indicator system and the calculation process

  6. mapDamage

    DEFF Research Database (Denmark)

    Ginolhac, Aurélien; Rasmussen, Morten; Gilbert, Tom

    2011-01-01

    Ancient DNA extracts consist of a mixture of contaminant DNA molecules, most often originating from environmental microbes, and endogenous fragments exhibiting substantial levels of DNA damage. The latter introduce specific nucleotide misincorporations and DNA fragmentation signatures in sequenci...... of the SAMtools suite and R environment and has been validated on both GNU/Linux and MacOSX operating systems....

  7. Angyomatous vocal polypus: a complete spontaneous regression

    Directory of Open Access Journals (Sweden)

    Edmir Américo Lourenço

    Full Text Available The authors describe a male patient who had malignant lymphoma seven years ago which remitted with chemotherapy.Two years ago he developed dysphonia. An unilateral, pediculate smooth red lesion on the right vocal fold was later discovered. Even without benefit of medicamentosus treatment, the patient refused surgery. In a reevaluation using rigid telescopy of the larynx two years later, the lesion had disappeared, completely and spontaneously. As there are no existing publications on this topic, this case report is an alert that surgery should be recommended with extreme caution in this type of vocal disease.

  8. Cerebrovascular gene expression in spontaneously hypertensive rats

    DEFF Research Database (Denmark)

    Grell, Anne-Sofie; Frederiksen, Simona Denise; Edvinsson, Lars

    2017-01-01

    in the middle cerebral arteries from hypertensive compared to normotensive rats. The gene expression of 72 genes was decreased and the gene expression of 97 genes was increased. The following genes with a fold difference ≥1.40 were verified by quantitative PCR; Postn, Olr1, Fas, Vldlr, Mmp2, Timp1, Serpine1......, Mmp11, Cd34, Ptgs1 and Ptgs2. The gene expression of Postn, Olr1, Fas, Vldlr, Mmp2, Timp1 and Serpine1 and the protein expression of LOX1 (also known as OLR1) were significantly increased in the middle cerebral arteries from spontaneously hypertensive rats compared to Wistar-Kyoto rats. In conclusion...

  9. Spontaneous light emission from fibers in MINOS

    International Nuclear Information System (INIS)

    Avvakumov, S.; Barrett, W.L.; Belias, T.; Bower, C.; Erwin, A.; Kordosky, M.; Lang, K.; Lee, R.; Liu, J.; Miller, W.; Mualem, L.; Nichol, R.; Nelson, J.; Pearce, G.; Proga, M.; Rebel, B.; Ruddick, K.; Smith, C.; Thomas, J.; Vahle, P.; Webb, R.

    2005-01-01

    We report on the observation and measurements of unexpected background rates in the MINOS Far Detector. The noise level at the Far Detector is significantly greater than that expected from natural radioactivity and intrinsic photomultiplier dark current. We have conducted a series of additional tests which demonstrate that the excess rate is caused by spontaneous light emission in the wavelength-shifting fibers, which are used to read out signals from scintillator strips. This noise due to fibers exhibits an exponential fall off with time with a decay time constant of the order of 100 days

  10. Fracture of maternal sternum during spontaneous delivery.

    Science.gov (United States)

    Stubert, J; Gerber, B

    2009-12-01

    We report of a maternal sternal fracture during a spontaneous delivery in a 31-year-old primipara without a suitable trauma. The putative mechanism of fracture was strong hyperflexion of the thoracic spine and additional cervical flexion with pushing the chin to the thorax due to active management of labour. The history of the healthy woman was free of related risk factors. A possible promoting factor might be pregnancy-induced bone loss. Although there were clear symptoms, the diagnosis of the fracture was delayed by a week because nobody took account of such a possibility.

  11. Web-Ice: Integrated Data Collection and Analysis for Macromolecular Crystallography

    International Nuclear Information System (INIS)

    Gonzalez, Ana; Gonzalez, Ana; Moorhead, Penjit; McPhillips, Scott E.; Song, Jinhu; Sharp, Ken; Taylor, John R.; Adams, Paul D.; Sauter, Nicholas K.; Soltis, S. Michael

    2007-01-01

    New software tools are introduced to facilitate diffraction experiments involving large numbers of crystals. While existing programs have long provided a framework for lattice indexing, Bragg spot integration, and symmetry determination, these initial data processing steps often require significant manual effort. This limits the timely availability of data analysis needed for high-throughput procedures, including the selection of the best crystals from a large sample pool, and the calculation of optimal data collection parameters to assure complete spot coverage with minimal radiation damage. To make these protocols more efficient, we developed a network of software applications and application servers, collectively known as Web-Ice. When the package is installed at a crystallography beamline, a programming interface allows the beamline control software (e.g., Blu-Ice/DCSS) to trigger data analysis automatically. Results are organized based on a list of samples that the user provides, and are examined within a Web page, accessible both locally at the beamline or remotely. Optional programming interfaces permit the user to control data acquisition through the Web browser. The system as a whole is implemented to support multiple users and multiple processors, and can be expanded to provide additional scientific functionality. Web-Ice has a distributed architecture consisting of several stand-alone software components working together via a well defined interface. Other synchrotrons or institutions may integrate selected components or the whole of Web-Ice with their own data acquisition software. Updated information about current developments may be obtained at http://smb.slac.stanford.edu/research/developments/webice

  12. Lymphocytes from wasted mice express enhanced spontaneous and {gamma}-ray-induced apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    Woloschak, G.E. [Argonne National Lab., IL (United States)]|[Loyola Univ. Medical Center, Maywood, IL (United States); Chang-Liu, Chin-Mei [Argonne National Lab., IL (United States); Chung, Jen; Libertin, C.R. [Loyola Univ. Medical Center, Maywood, IL (United States)

    1993-09-01

    Mice bearing the autosomal recessive mutation wasted (wst/wst) display a disease pattern including faulty repair of DNA damage in lymphocytes after radiation exposure, neurologic abnormalities, and immunodeficiency. Many of the features of this mouse model have suggested a premature or increased spontaneous frequency of apoptosis in thymocytes; past work has shown an inability to establish cultured T cell lines, an abnormally high death rate of stimulated T cells in culture, and an increased sensitivity of T cells to the killing effects of ionizing radiations in wst/wst mice relative to controls. The experiments reported here were designed to examine splenic and thymic lymphocytes from wasted and control mice for signs of early apoptosis. Our results revealed enhanced expression of Rp-8 mRNA (associated with apoptosis) in thymic lymphocytes and reduced expression in splenic lymphocytes of wst/wst mice relative to controls; expression of Rp-2 and Td-30 mRNA (induced during apoptosis) were not detectable in spleen or thymus. Higher spontaneous DNA fragmentation was observed in wasted mice than in controls; however, {gamma}-ray-induced DNA fragmentation peaked at a lower dose and occurred to a greater extent in wasted mice relative to controls. These results provide evidence for high spontaneous and {gamma}-ray-induced apoptosis in T cells of wasted mice as a mechanism underlying the observed lymphocyte and DNA repair abnormalities.

  13. Recurrent Spontaneous Pneumothorax during the Recovery Phase of ARDS Due to H1N1 Infection

    Directory of Open Access Journals (Sweden)

    Canan Bor

    2013-03-01

    Full Text Available The pregnant patients are prone to influenza A (H1N1 virus infection, which may rapidly progress to lower respiratory tract infection and subsequent respiratory failure and acute respiratory distress syndrome (ARDS. Pneumothorax might develop in ARDS under mechanical ventilation. But post-ARDS pneumothorax in spontaneously breathing patient has not been reported in the literature. We report a 31-year old pregnant woman infected with influenza A (H1N1 virus and progressed to ARDS. Mechanical ventilation with high PEEP improved patient's gas exchange parameters within 3 weeks. However spontaneous pneumothorax was developed one week after she weaned off the ventilator. After successful drainage therapy, the patient was discharged. However she re-admitted to the hospital because of a recurrent pneumothorax one week later. She was discharged in good health after being treated with negative continuous pleural aspiration for 10 days. Influenza might cause severe pulmonary infection and death. In addition to diffuse alveolar damage, sub-pleural and intrapulmonary air cysts might occur in influenza-related ARDS and may lead to spontaneous pneumothorax. This complication should always be considered during the recovery period of ARDS and a long-term close follow-up is necessary.

  14. Spontaneous cooperation for prosocials, but not for proselfs: Social value orientation moderates spontaneous cooperation behavior

    Science.gov (United States)

    Mischkowski, Dorothee; Glöckner, Andreas

    2016-01-01

    Cooperation is essential for the success of societies and there is an ongoing debate whether individuals have therefore developed a general spontaneous tendency to cooperate or not. Findings that cooperative behavior is related to shorter decision times provide support for the spontaneous cooperation effect, although contrary results have also been reported. We show that cooperative behavior is better described as person × situation interaction, in that there is a spontaneous cooperation effect for prosocial but not for proself persons. In three studies, one involving population representative samples from the US and Germany, we found that cooperation in a public good game is dependent on an interaction between individuals’ social value orientation and decision time. Increasing deliberation about the dilemma situation does not affect persons that are selfish to begin with, but it is related to decreasing cooperation for prosocial persons that gain positive utility from outcomes of others and score high on the related general personality trait honesty/humility. Our results demonstrate that the spontaneous cooperation hypothesis has to be qualified in that it is limited to persons with a specific personality and social values. Furthermore, they allow reconciling conflicting previous findings by identifying an important moderator for the effect. PMID:26876773

  15. Spontaneous regression of intracranial malignant lymphoma

    International Nuclear Information System (INIS)

    Kojo, Nobuto; Tokutomi, Takashi; Eguchi, Gihachirou; Takagi, Shigeyuki; Matsumoto, Tomie; Sasaguri, Yasuyuki; Shigemori, Minoru.

    1988-01-01

    In a 46-year-old female with a 1-month history of gait and speech disturbances, computed tomography (CT) demonstrated mass lesions of slightly high density in the left basal ganglia and left frontal lobe. The lesions were markedly enhanced by contrast medium. The patient received no specific treatment, but her clinical manifestations gradually abated and the lesions decreased in size. Five months after her initial examination, the lesions were absent on CT scans; only a small area of low density remained. Residual clinical symptoms included mild right hemiparesis and aphasia. After 14 months the patient again deteriorated, and a CT scan revealed mass lesions in the right frontal lobe and the pons. However, no enhancement was observed in the previously affected regions. A biopsy revealed malignant lymphoma. Despite treatment with steroids and radiation, the patient's clinical status progressively worsened and she died 27 months after initial presentation. Seven other cases of spontaneous regression of primary malignant lymphoma have been reported. In this case, the mechanism of the spontaneous regression was not clear, but changes in immunologic status may have been involved. (author)

  16. Spontaneous bending of pre-stretched bilayers.

    Science.gov (United States)

    DeSimone, Antonio

    2018-01-01

    We discuss spontaneously bent configurations of pre-stretched bilayer sheets that can be obtained by tuning the pre-stretches in the two layers. The two-dimensional nonlinear plate model we use for this purpose is an adaptation of the one recently obtained for thin sheets of nematic elastomers, by means of a rigorous dimensional reduction argument based on the theory of Gamma-convergence (Agostiniani and DeSimone in Meccanica. doi:10.1007/s11012-017-0630-4, 2017, Math Mech Solids. doi:10.1177/1081286517699991, arXiv:1509.07003, 2017). We argue that pre-stretched bilayer sheets provide us with an interesting model system to study shape programming and morphing of surfaces in other, more complex systems, where spontaneous deformations are induced by swelling due to the absorption of a liquid, phase transformations, thermal or electro-magnetic stimuli. These include bio-mimetic structures inspired by biological systems from both the plant and the animal kingdoms.

  17. Surgery for spontaneous intracerebral hemorrhage: Emerging trends

    Directory of Open Access Journals (Sweden)

    Girish Menon

    2017-01-01

    Full Text Available In spite of advances in imaging and surgical techniques, spontaneous intracerebral hemorrhage (SICH has defied attempts to find a scientifically proven effective therapy. The pathophysiology of SICH suggests that early removal of the clot with minimal additional surgical trauma should prove beneficial. Trials in this direction have been few, and for some unknown reason, surgery has not proved to be superior to best medical management in most of these trials. This has led to substantial variability in the management of ICH throughout the world, and the treatment of SICH remains a controversy. SICH encompasses spectra of possible clot locations with varying volumes. Surgery so far has been reserved only for patients with large hematomas and impending brain herniation. Critical analysis of the earlier studies has now shown that surgery does help in clots in certain locations and of particular volume and when done at an optimal time. Poor grade patients with large hematomas, earlier considered poor surgical candidates are being taken up for aggressive decompressive craniectomies with fair results. In addition, minimally invasive surgical techniques complemented by thrombolytic techniques seem to providing surprisingly good results. Overall surgery seems to be going through a period of renaissance with respect to primary spontaneous ICHs.

  18. Spontaneous unscheduled DNA synthesis in human lymphocytes

    International Nuclear Information System (INIS)

    Forell, B.; Myers, L.S. Jr.; Norman, A.

    1979-01-01

    The rate of spontaneous unscheduled DNA synthesis in human lymphocytes was estimated from measurements of tritiated thymidine incorporation into double-stranded DNA (ds-DNA) during incubation of cells in vitro. The contribution of scheduled DNA synthesis to the observed incorporation was reduced by inhibiting replication with hydroxyurea and by separating freshly replicated single-stranded DNA (ss-DNA) from repaired ds-DNA by column chromatography. The residual contribution of scheduled DNA synthesis was estimated by observing effects on thymidine incorporation of: (a) increasing the rate of production of apurinic sites, and alternatively, (b) increasing the number of cells in S-phase. Corrections based on estimates of endogenous pool size were also made. The rate of spontaneous unscheduled DNA synthesis is estimated to be 490 +- 120 thymidine molecules incorporated per cell per hour. These results compare favorably with estimates made from rates of depurination and depyrimidination of DNA, measured in molecular systems if we assume thymidine is incorporated by a short patch mechanism which incorporates an average of four bases per lesion

  19. Spontaneous ad hoc mobile cloud computing network.

    Science.gov (United States)

    Lacuesta, Raquel; Lloret, Jaime; Sendra, Sandra; Peñalver, Lourdes

    2014-01-01

    Cloud computing helps users and companies to share computing resources instead of having local servers or personal devices to handle the applications. Smart devices are becoming one of the main information processing devices. Their computing features are reaching levels that let them create a mobile cloud computing network. But sometimes they are not able to create it and collaborate actively in the cloud because it is difficult for them to build easily a spontaneous network and configure its parameters. For this reason, in this paper, we are going to present the design and deployment of a spontaneous ad hoc mobile cloud computing network. In order to perform it, we have developed a trusted algorithm that is able to manage the activity of the nodes when they join and leave the network. The paper shows the network procedures and classes that have been designed. Our simulation results using Castalia show that our proposal presents a good efficiency and network performance even by using high number of nodes.

  20. Spontaneous and stimulated emission from quasifree electrons

    Science.gov (United States)

    Friedman, A.; Gover, A.; Kurizki, G.; Ruschin, S.; Yariv, A.

    1988-04-01

    This article presents a unified formulation and review of an extensive class of radiation effects and devices based on free or quasifree electrons. The effects and devices reviewed include slow-wave radiators [such as Čerenkov, Smith-Purcell, and TWT (traveling-wave tube) effects and devices], periodic bremsstrahlung radiators [such as undulator radiation, magnetic bremsstrahlung FEL's (free-electron lasers), and coherent bremsstrahlung in the crystal lattice], and transverse-binding radiators [such as the CRM (cyclotron resonance maser) and channeling radiation]. Starting from a general quantum-electrodynamic model, both quantum and classical effects and operating regimes of these radiation devices are described. The article provides a unified physical description of the interaction kinematics, and presents equations for the characterization of spontaneous and stimulated radiative emission in these various effects and devices. Universal relations between the spontaneous and stimulated emission parameters are revealed and shown to be related (in the quantum limit) to Einstein relations for atomic radiators and (in the classical limit) to the relations derived by Madey for magnetic bremsstrahlung FEL for on-axis radiative emission. Examples for the application of the formulation are given, estimating the feasibility of channeling radiation x-ray laser and optical regime Smith-Purcell FEL, and deriving the gain equations of magnetic bremsstrahlung FEL and CRM for arbitrary electron propagation direction, structure (wiggler) axis, and radiative emission angle.