bluuebunny/crossref_metadata_2025_split huggingface dataset:
Computational studies on the molecular insights of aptamer induced poly(N-isopropylacrylamide)-graft-graphene oxide for on/off- switchable whole-cell cancer diagnostics
Authors: Putri Athika Darumas , Murti Bayu Tri , Kanchi Suvardhan , Sabela Myalowenkosi I. , Bisetty Krishna , Tiwari Ashutosh , Inamuddin  , Asiri Abdullah M. 
Published: May 2019

AbstractThis work deals with first-principles and in silico studies of graphene oxide-based whole-cell selective aptamers for cancer diagnostics utilising a tunable-surface strategy. Herein, graphene oxide (GO) was constructed as a surface-based model with poly(N-isopropylacrylamide) (PNIPAM) covalently grafted as an “on/off”-switch in triggering interactions with the cancer-cell protein around its lower critical solution temperature. The atomic building blocks of the aptamer and the PNIPAM adsorbed onto the GO was investigated at the density functional theory (DFT) level. The presence of the monomer of PNIPAM stabilised the system’s π-π interaction between GO and its nucleobases as confirmed by higher bandgap energy, satisfying the eigenvalues of the single-point energy observed rather than the nucleobase and the GO complex independently. The unaltered geometrical structures of the surface emphasise the physisorption type interaction between the nucleobase and the GO/NIPAM surface. The docking result for the aptamer and the protein, highlighted the behavior of the PNIPAM-graft-GO is exhibiting globular and extended conformations, further supported by molecular dynamics (MD) simulations. These studies enabled a better understanding of the thermal responsive behavior of the polymer-enhanced GO complex for whole-cell protein interactions through computational methods.
Spatial Uniformity Assessment of Particles Distributed in a Spherical Fuel Element Using a Non-Destructive Approach
Authors: Zhao Xuzhi , Peng Yahui , Wang Xian-gang , Zhu Libing , Chen Houjin 
Published: May 2019

AbstractIn many manufacturing procedures, a large number of identical particles need to be disseminated uniformly into a given space. The uniformity of the spatial distribution of the particles can be critical to the properties of the final products. We proposed an image processing-based non-destructive technique to evaluate the particles’ spatial uniformity in a spherical space imaged with computed tomography. Both graphic (qualitative) and numerical (quantitative) methods were developed to demonstrate the (non-) uniformity of the particles. Simulation results indicated that the technique helped detecting the non-uniformity in the particles’ spatial distribution accurately. We conclude that the proposed technique can be used to test whether a number of particles in a sphere are uniformly distributed statistically and graphically.
Time-restricted feeding improves adaptation to chronically alternating light-dark cycles
Authors: Schilperoort Maaike , van den Berg Rosa , Dollé Martijn E. T. , van Oostrom Conny T. M. , Wagner Karina , Tambyrajah Lauren L. , Wackers Paul , Deboer Tom , Hulsegge Gerben , Proper Karin I. , van Steeg Harry , Roenneberg Till , Biermasz Nienke R. , Rensen Patrick C. N. , Kooijman Sander , van Kerkhof Linda W. M. 
Published: May 2019

AbstractDisturbance of the circadian clock has been associated with increased risk of cardio-metabolic disorders. Previous studies showed that optimal timing of food intake can improve metabolic health. We hypothesized that time-restricted feeding could be a strategy to minimize long term adverse metabolic health effects of shift work and jetlag. In this study, we exposed female FVB mice to weekly alternating light-dark cycles (i.e. 12 h shifts) combined with ad libitum feeding, dark phase feeding or feeding at a fixed clock time, in the original dark phase. In contrast to our expectations, long-term disturbance of the circadian clock had only modest effects on metabolic parameters. Mice fed at a fixed time showed a delayed adaptation compared to ad libitum fed animals, in terms of the similarity in 24 h rhythm of core body temperature, in weeks when food was only available in the light phase. This was accompanied by increased plasma triglyceride levels and decreased energy expenditure, indicating a less favorable metabolic state. On the other hand, dark phase feeding accelerated adaptation of core body temperature and activity rhythms, however, did not improve the metabolic state of animals compared to ad libitum feeding. Taken together, restricting food intake to the active dark phase enhanced adaptation to shifts in the light-dark schedule, without significantly affecting metabolic parameters.
Changes in soil taxonomic and functional diversity resulting from gamma irradiation
Authors: Ogwu Matthew Chidozie , Kerfahi Dorsaf , Song HoKyung , Dong Ke , Seo Hoseong , Lim Sangyong , Srinivasan Sathiyaraj , Kim Myung Kyum , Waldman Bruce , Adams Jonathan M. 
Published: May 2019

AbstractLittle is known of the effects of ionizing radiation exposure on soil biota. We exposed soil microcosms to weekly bursts of60Co gamma radiation over six weeks, at three levels of exposure (0.1 kGy/hr/wk [low], 1 kGy/hr/wk [medium] and 3 kGy/hr/wk [high]). Soil DNA was extracted, and shotgun metagenomes were sequenced and characterised using MG-RAST. We hypothesized that with increasing radiation exposure there would be a decrease in both taxonomic and functional diversity. While bacterial diversity decreased, diversity of fungi and algae unexpectedly increased, perhaps because of release from competition. Despite the decrease in diversity of bacteria and of biota overall, functional gene diversity of algae, bacteria, fungi and total biota increased. Cycles of radiation exposure may increase the range of gene functional strategies viable in soil, a novel ecological example of the effects of stressors or disturbance events promoting some aspects of diversity. Moreover, repeated density-independent population crashes followed by population expansion may allow lottery effects, promoting coexistence. Radiation exposure produced large overall changes in community composition. Our study suggests several potential novel radiation-tolerant groups: in addition to Deinococcus-Thermus, which reached up to 20% relative abundance in the metagenome, the phyla Chloroflexi (bacteria), Chytridiomycota (fungi) and Nanoarcheota (archaea) may be considered as radiation-tolerant.
Metabolic Infrastructure of Pregnant Women With Trisomy 21 Fetuses; Metabolomic Analysis
Authors: Nemutlu Emirhan , Orgul Gokcen , Recber Tuba , Aydin Emine , Ozkan Ece , Turgal Mert , Alikasifoglu Mehmet , Kir Sedef , Beksac Mehmet Sinan 
Published: May 2019

AbstractWe aimed to configure impaired/altered metabolomic profiles of pregnant women carrying Down syndrome (DS) fetuses. The study involved 21 and 32 pregnant women with DS and euploid fetuses, respectively, as determined by prenatal screening and diagnosis as part of an antenatal care program. Metabolomic analyses were carried out using gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-qTOF-MS) methods. A total of 95 metabolites were identified. GC-MS analysis indicated that levels of 2-hydroxybutyric acid, benzoic acid, nonanoic acid, 3-hydroxybutyric acid, and 2-ketoisocaproic acid were increased in the DS group, where beta-alanine, threonic acid, oxalic acid, alpha-tocopherol, uracil, 2-piperidone, and creatinine were decreased. However, LC-qTOF-MS analysis showed that lipid-related metabolites were decreased in women carrying DS fetuses, whereas creatine, N4-phosphoagmatine, citrate, 2,5-dioxopentanoate, 2-furoate, pyruvate, and fructose levels were increased. Pathway analysis was also performed using metabolites whose levels were significantly altered (p<0.05) between the groups, and the findings indicated that the biosynthesis pathways of aminoacyl-tRNA and “valine-leucine-isoleucine”, and metabolism pathways of “glycine-serine-threonine”, nitrogen, “alanine-aspartate-glutamate”, propanoate, glycerophospholipid, cysteine, methionine, and phenylalanine were significantly altered. Our findings indicate a special type of metabolic status/syndrome in pregnant women with Down syndrome fetuses. It could be speculated that altered metabolic status might influence both gametogenesis and embryogenesis. Down syndrome is a complex genetic disorder that is important to detect prenatally, but may also be prevented by taking necessary precautions prior to pregnancy.
Richtigstellung: Saphenofemorale Rezidive nach endovenöser thermischer Therapie und nach chirurgischer Therapie
Authors: Hartmann K. 
Published: May 2019

Thermische Ablation kostengünstiger als chirurgische Operation!Die Arbeitsgruppe Mumme, Mühlberger, Sidhwa und Hummel haben mit ihrer Arbeit „Alarmierend hohe Rate saphenofemoraler Rezidive nach endovenöser Lasertherapie“ (Phlebologie 2019;48:18–22) mehrere Behauptungen aufgestellt, die nochmals genauer beleuchtet werden müssen.
European Working Group on Clinical Cell Analysis: Consensus Protocol for the Flow Cytometric Characterisation of Platelet Function
Authors: Schmitz Gerd , Rothe Gregor , Ruf Andreas , Barlage Stefan , Tschöpe Diethelm , Clemetson Kenneth J. , Goodall Alison H. , Michelson Alan D. , Nurden Alan T. , Shankey Vincent T. ,   for the European Working Group on Clinical Cell Analysis
Published: May 2019

IntroductionAn increased or disturbed activation and aggregation of platelets plays a major role in the pathophysiology of thrombosis and haemostasis and is related to cardiovascular disease processes. In addition to qualitative disturbances of platelet function, changes in thrombopoiesis or an increased elimination of platelets, (e. g., in autoimmune thrombocytopenia), are also of major clinical relevance. Flow cytometry is increasingly used for the specific characterisation of phenotypic alterations of platelets which are related to cellular activation, haemostatic function and to maturation of precursor cells. These new techniques also allow the study of the in vitro response of platelets to stimuli and the modification thereof under platelet-targeted therapy as well as the characterisation of platelet-specific antibodies. In this protocol, specific flow cytometric techniques for platelet analysis are recommended based on a description of the current state of flow cytometric methodology. These recommendations are an attempt to promote the use of these new techniques which are at present broadly evaluated for diagnostic purposes. Furthermore, the definition of the still open questions primarily related to the technical details of the method should help to promote the multi-center evaluation of procedures with the goal to finally develop standardized operation procedures as the basis of interlaboratory reproducibility when applied to diagnostic testing.
Low Molecular Weight Heparin Decreases Proximal and Distal Deep Venous Thrombosis Following Total Knee Arthroplasty
Authors: Howard Andrew W. , Aaron Shawn D. 
Published: May 2019

SummaryObjectives: To assess the efficacy and safety of low molecular weight heparin (LMWH) as deep venous thrombosis (DVT) prophylaxis following total knee arthroplasty. Data sources: Medline 1986 to June 1997, Embase, and manufacturers were used to identify randomized controlled trials. Review methods: Trials included were randomized studies of LMWH with routine radiological screening for DVT. Placebo or active controls were included. Two reviewers independently screened trials for inclusion, and assessed their quality. Pooled relative risk estimates of DVT and proximal DVT rates were calculated using a DerSimonian and Laird random effects model. Sensitivity of the results to the type of control used and the quality of the trial was assessed. Results: The relative risk of DVT for a patient given LMWH is 0.73 (95% CI 0.66 to 0.80) when compared with patients treated with adjusted dose heparin or warfarin controls. The relative risk for proximal DVT is 0.58 (95% CI 0.38 to 0.90). The relative risk of pulmonary emboli in the LMWH group was 0.55 (95% C.I. 0.20 to 1.57). No excess of bleeding was recorded in the LMWH group. Conclusions: Low molecular weight heparin is more efficacious than either adjusted dose heparin or adjusted dose warfarin, when used to prevent DVT and proximal DVT following total knee arthroplasty.
A 20.7 kb Deletion within the Factor VIII Gene Associated with LINE-1 Element Insertion
Authors: Water Neil Van de , Williams Ruth , Ockelford Paul , Browett Peter 
Published: May 2019

SummaryLarge deletions within the factor VIII gene account for approximately 5% of the mutations causing haemophilia A. The characterization of such mutations can provide insights into the molecular mechanisms of these and other deletions in man. We have analyzed a 20.7 kb deletion spanning exons 15 to 20 within the factor VIII gene in a patient with severe haemophilia A. Long range PCR was used to investigate the extent of the deletion and to provide a template for sequencing across the deletion breakpoint. A 38-base insertion homologous to the 3’ region of a LINE-1 (L1) element was detected at the breakpoint of the deletion. Normal sequence at the 5’ breakpoint in intron 14 was homologous to an L1 flanking region and normal sequence at the 3’ breakpoint in intron 20 was homologous to an adjacent sequence within the same L1 flanking region. A molecular mechanism for the deletion involving retrotransposition of a readthrough product of an L1 element plus its 3’ flanking region is suggested.
Partial Reconstitution of Factor VIII Activity from a Mild Crm+ Hemophilia A Patient by Replacement of the Defective A2 Domain
Authors: Pieneman W. C. , Fay P. , Briët E. , Reitsma P. H. , Bertina R. M. 
Published: May 2019

SummaryWe further characterised the abnormal factor VIII molecule (factor VIII Leiden) of a Crm+, mild hemophilia A patient with a factor VIII activity of 0.18 IU/ml and a factor VIII antigen of 0.95 IU/ml. Mutation analysis of the coding region, promoter and 3’ untranslated region of the factor VIII gene revealed the presence of a C to T substitution at codon 527. This nucleotide change predicts the replacement of an arginine to tryptophan in the A2 domain close to a suggested binding site for factor IXa. Since a previous study of this mutant factor VIII protein suggested that this protein had a reduced affinity for factor IXa, position 527 in the protein might be involved in the interaction with factor IXa.In this study we gathered evidence for our hypothesis that the Arg to Trp mutation at position 527 is the cause of the reduced activity of factor VIII Leiden. Replacement of the mutated A2 domain by wild type A2 domain partially corrected the defect.Factor VIII from normal and factor VIII Leiden plasma was concentrated by cryoprecipitation, activated with thrombin and incubated with excess wild type A2 domain. Competition with excess isolated human A2 domain resulted in a partial reconstitution of the factor VIIIa activity of thrombin treated factor VIII Leiden. This supports the hypothesis that the mutation in the A2 domain is the cause of the reduced factor VIII activity.
Monoclonal Antibodies against Beta-2-Glycoprotein I: Use as Reference Material for Lupus Anticoagulant Tests
Authors: Arnout J. , Vanrusselt M. , Wittevrongel C. , Vermylen J. 
Published: May 2019

SummaryThe laboratory diagnosis of lupus anticoagulants (LA) remains difficult despite internationally accepted guidelines for its detection. Several interlaboratory surveys have shown poor agreement between laboratories. Further standardization of LA testing will to a large extent depend on better insights on the mechanisms by which LA affect phospholipid-dependent coagulation assays as well as on the availability of well characterized and internationally accepted reference materials and control specimens. We recently raised a series of murine monoclonal antibodies against human β2GPI (anti-β2GPI moabs), a phospholipid-binding protein directly involved in the interaction between certain lupus anticoagulants and phospholipids. In this study we report on the use of LA positive anti-β2GPI moabs as easy to handle reference and control material. The relative LA responsiveness of various phospholipid-dependent clotting assays was determined on plasmas spiked with such moabs and compared well with that determined on LA positive plasma samples. Plasmas spiked with LA positive anti-β2GPI moabs were also used as control specimens to study the interlaboratory precision of LA testing. With these control specimens, low interassay coefficients of variation were obtained. Our results indicate that LA positive anti-β2GPI moabs have potential for the production of control specimens that could be made available to routine hemostasis laboratories to assess intra-laboratory precision of LA testing and to manufacturers to control batch-to-batch variability of their reagents.
Antibodies against Fibrinogen in Pregnant Women, in Post Delivery Women and in the Newborns
Authors: Kondera-Anasz Zdzislawa 
Published: May 2019

SummaryPregnancy and delivery have measurable effects on haemostatic and immunological changes. Degradation of fibrinogen induces significant structural and conformational modulation and leads to the progressive loss of antigenic sites present on the parent molecule but also exposes some new sites. These neoantigens may be recognized by the immune system and may be elicited by the autologous host manifested by the production of autoantibodies. Therefore in the present study, in pregnant and post delivery women and in the newborns, levels of antibodies against fibrinogen, fibrin(ogen) degradation products (FDP) and fibrin degradation products (D-dimer) were examined.Enzyme immunoassay (ELISA) was used to detect and quantitate autoantibodies against fibrinogen (class G immunoglobulin) in human sera. In all sera there were found varying concentrations of autoantibodies and their levels were significantly higher in all pregnant women in comparison with non-pregnant ones. Significantly higher levels were found in Rh immunized and clinically complicated pregnancies.The level of autoantibodies, coagulation and fibrinolytic system components were higher in post delivery women than in normal pregnant women. Also antibodies to fibrinogen were studied in cord serum of newborns in different terms of delivery. The low levels of antibodies in all newborns raise questions of possible foetal-maternal immunologic interactions. Positive correlation between mothers and newborns was demonstrated after delivery at gestational age from 34th to 41st week, and negative in 42nd and more week. There were no significant differences in antibody level among the newborns delivered by the same mothers.It was found that autoantibodies bind selectively to the fibrinogen and fibrinogen fragments X, Y and D. These autoantibodies may represent a new interface between the coagulation and the immune systems which may be significant in controlling the pathologic activities of the cleavage fragments.
Adhesion of ADP-activated Platelets to Intact Endothelium under Stagnation Point Flow In Vitro Is Mediated by the Integrin αIIbβ3
Authors: Reininger Armin J. , Korndörfer Markus A. , Wurzinger Laurenz J. 
Published: May 2019

SummaryAs we demonstrated earlier, platelets adhere to intact endothelium provided they are activated and convectively transported against the endothelial surface. To identify the platelet receptors involved we superfused cultured endothelium with activated platelet rich plasma (PRP) by means of the Stagnation Point Flow Adhesio- Aggregometer while blocking various platelet receptors. Inhibition was performed with the tetrapeptide RGDS, the non-peptide Ro-43-8857, or a monoclonal antibody directed against integrin αIIbβ3. Platelet deposition was video-recorded and quantified by image analysis. Infusion of RGDS or Ro-43-8857 into ADP-stimulated PRP completely prevented adhesion as well as subsequent aggregation. Interrupting the inhibitor infusion while ADP stimulation persisted, prompted adhesion and aggregation, demonstrating the reversibility of the inhibition. Platelet adhesion was irreversibly blocked by preincubation of the PRP with the moab against αIIbβ3. Its specific binding was confirmed by immuno-electron microscopy. Our results suggest that platelet adhesion to intact endothelium is mediated via platelet integrin αIIbβ3.
Morphological and Biochemical Features Affecting the Antithrombotic Properties of the Aorta in Adult Rabbits and Rabbit Pups
Authors: Nitschmann E. , Berry L. , Bridge S. , Hatton M. W. C. , Richardson M. , Monagle P. , Chan A. K. C. , Andrew M. 
Published: May 2019

SummaryWe hypothesised that there are important physiologic differences in arterial wall structure and function with respect to antithrombotic activity in the very young (pre-puberty) compared to adults. Electron microscopy, gel electrophoresis, and activity assays were used to examine differences in aorta structure and function comparing prepubertal rabbits (pups) to adult rabbits. Differences in endothelial function, extracellular matrix structure, proteoglycan (PG) distribution and glycosaminoglycan (GAG) content and function were shown. In both intima and media, total PG, chondroitin sulfate (CS) PG and heparan sulfate (HS) PG content were significantly increased in pups compared to adult rabbits. These findings corresponded to increased concentrations by mass analyses of CS GAG and DS GAG in aortas from pups. There was also a significant increase in antithrombin activity in pups due to HS GAG. In conclusion, differences in both structure and antithrombin activity of aortas from pups compared to adult rabbits suggest that young arteries may have greater antithrombotic potential that is, at least in part, related to increased HS GAG.
Ancylostoma caninum Anticoagulant Peptide Blocks Metastasis In Vivo and Inhibits Factor Xa Binding to Melanoma Cells In Vitro
Authors: Donnelly Kathleen M. , Bromberg Michael E. , Milstone Aaron , McNiff Jennifer Madison , Terwilliger Gordon , Konigsberg William H. , Cappello Michael 
Published: May 2019

SummaryWe evaluated the in vivo anti-metastatic activity of recombinant Ancylostoma caninum Anticoagulant Peptide (rAcAP), a potent (Ki
= 265 pM) and specific active site inhibitor of human coagulation factor Xa originally isolated from bloodfeeding hookworms. Subcutaneous injection of SCID mice with rAcAP (0.01-0.2 mg/mouse) prior to tail vein injection of LOX human melanoma cells resulted in a dose dependent reduction in pulmonary metastases. In order to elucidate potential mechanisms of rAcAP’s anti-metastatic activity, experiments were carried out to identify specific interactions between factor Xa and LOX. Binding of biotinylated factor Xa to LOX monolayers was both specific and saturable (Kd
= 15 nM). Competition experiments using antibodies to previously identified factor Xa binding proteins, including factor V/Va, effector cell protease receptor-1, and tissue factor pathway inhibitor failed to implicate any of these molecules as significant binding sites for Factor Xa. Functional prothrombinase activity was also supported by LOX, with a half maximal rate of thrombin generation detected at a factor Xa concentration of 2.4 nM. Additional competition experiments using an excess of either rAcAP or active site blocked factor Xa (EGR-Xa) revealed that most of the total factor Xa binding to LOX is mediated via interaction with the enzyme’s active site, predicting that the vast majority of cell-associated factor Xa does not participate directly in thrombin generation. In addition to establishing two distinct mechanisms of factor Xa binding to melanoma, these data raise the possibility that rAcAP’s antimetastatic effect in vivo might involve novel non-coagulant pathways, perhaps via inhibition of active-site mediated interactions between factor Xa and tumor cells.