bluuebunny/crossref_metadata_2025 huggingface dataset:
Genome-wide association study of developmental dysplasia of the hip identifies an association with GDF5
Authors: Hatzikotoulas Konstantinos , Roposch Andreas ,   The DDH Case Control Consortium, Wainwright Andrew , Theologis Tim , Clarke Nicholas M. P. , Dwyer Jonathan S. M. , Hashemi-Nejad Aresh , Kiely Nigel , Katchburian Marcos , Nicolaou Nicolas , Page Johnathan , Gargan Martin , Bruce Colin , Sanghrajka Anish , Marshall Paul , Flowers Mark , Malaga-Shaw Olivia , Mitchell Piers , Ben Holroyd  , Ramachandran Manoj , Shah Karan M. , Clark Matthew J. , Bratherton Selina , Limbani Vasanti , Steinberg Julia , Zengini Eleni , Warsame Kaltuun , Ratnayake Madhushika , Tselepi Maria , Schwartzentruber Jeremy , Loughlin John , Eastwood Deborah M. , Zeggini Eleftheria , Wilkinson J. Mark
Published: May 2018

Developmental dysplasia of the hip (DDH) is the most common skeletal developmental disease. However, its genetic architecture is poorly understood. We conduct the largest DDH genome-wide association study to date and replicate our findings in independent cohorts. We find the heritable component of DDH attributable to common genetic variants to be 55% and distributed equally across the autosomal and X-chromosomes. We identify replicating evidence for association between GDF5 promoter variation and DDH (rs143384, effect allele A, odds ratio 1.44, 95% confidence interval 1.34–1.56, P = 3.55 × 10−22). Gene-based analysis implicates GDF5 (P = 9.24 × 10−12), UQCC1 (P = 1.86 × 10−10), MMP24 (P = 3.18 × 10−9), RETSAT (P = 3.70 × 10−8) and PDRG1 (P = 1.06 × 10−7) in DDH susceptibility. We find shared genetic architecture between DDH and hip osteoarthritis, but no predictive power of osteoarthritis polygenic risk score on DDH status, underscoring the complex nature of the two traits. We report a scalable, time-efficient recruitment strategy and establish for the first time to our knowledge a robust DDH genetic association locus at GDF5.
Molecularly imprinted polymer nanoparticle-based assay (MINA): application for fumonisin B1 determination
Authors: Munawar Hasim , Smolinska-Kempisty Katarzyna , Cruz Alvaro Garcia , Canfarotta Francesco , Piletska Elena , Karim Khalku , Piletsky Sergey A.
Published: May 2018

The enzyme-linked immunosorbent assay (ELISA) has been used as a standard tool for monitoring food and animal feed contamination from the carcinogenic fumonisin B1 (FB1).
Anomalous thermally-activated NIR emission of ESIPT modulated Nd-complexes for optical fiber sensing devices
Authors: Sun Si-Si , Zhang Jian-Hua , Wang Zheng , Yu Yong-Qin , Zhu Cheng-Yi , Pan Mei , Su Cheng-Yong
Published: May 2018

Highly sensitized NIR emission was modulated using an ESIPT ligand in a Nd-complex, to achieve abnormal NIR enhancement with temperature increasing from 77 to 300 K for the first time.
Synthesis of lipid–black phosphorus quantum dot bilayer vesicles for near-infrared-controlled drug release
Authors: Geng Shengyong , Wu Lie , Cui Haodong , Tan Wenyong , Chen Tianfeng , Chu Paul K. , Yu Xue-Feng
Published: May 2018

Black phosphorus quantum dots are incorporated into liposomal bilayers to produce a drug delivery system with excellent near-infrared (NIR) photothermal properties and drug release capability controlled by light.
Insight into the effect of intercalated alkaline cations of layered manganese oxides on the oxygen reduction reaction and oxygen evolution reaction
Authors: Kosasang Soracha , Ma Nattapol , Wuamprakhon Phatsawit , Phattharasupakun Nutthaphon , Maihom Thana , Limtrakul Jumras , Sawangphruk Montree
Published: May 2018

The effect of the intercalated alkaline cations of multilayered manganese oxide (MnOx) towards the oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) was investigated.
Water desalination using graphene nanopores: influence of the water models used in simulations
Authors: K. Vishnu Prasad , Kannam Sridhar Kumar , Hartkamp Remco , Sathian Sarith P.
Published: May 2018

Water desalination using graphene nanopores was studied using different water models. The water permeation was found to be influenced by the bulk transport properties and the hydrogen-bond dynamics of the simulated water.
Solute clustering in undersaturated solutions – systematic dependence on time, temperature and concentration
Authors: Svärd Michael , Renuka Devi K. , Khamar Dikshitkumar , Mealey Donal , Cheuk Dominic , Zeglinski Jacek , Rasmuson Åke C.
Published: May 2018

The appearance, growth and steady-state size distribution of clusters of organic molecules in solution depend on composition, temperature and pre-treatment.
Towards a full quantitative description of single-molecule reaction kinetics in biological cells
Authors: Grebenkov Denis S. , Metzler Ralf , Oshanin Gleb
Published: May 2018

The first-passage time (FPT),i.e., the moment when a stochastic process reaches a given threshold value for the first time, is a fundamental mathematical concept with immediate applications. We present a robust explicit approach for obtaining the full distribution of FPT to a partially reactive target in a cylindrical-annulus domain.
Amine-functionalized Zn(ii) MOF as an efficient multifunctional catalyst for CO2 utilization and sulfoxidation reaction
Authors: Patel Parth , Parmar Bhavesh , Kureshy Rukhsana I. , Khan Noor-ul H. , Suresh Eringathodi
Published: May 2018

Zn(ii)-based 3D MOF was used as a heterogenous multifunctional catalyst for the cycloaddition of CO2 with epoxides and sulfoxidation reaction.
Efficient yellow electroluminescence of four iridium(iii) complexes with benzo[d]thiazole derivatives as main ligands
Authors: Niu Zhi-Gang , Chen Jun , Tan Peng , Sun Wei , Zheng You-Xuan , Li Gao-Nan , Zuo Jing-Lin
Published: May 2018

Four yellow iridium(iii) complexes with benzo[d]thiazole derivatives as the main ligands display good device performances with a maximum current efficiency of up to 69.8 cd A−1and a maximum external quantum efficiency of up to 24.3%.
1,3,5-Trimethoxybenzene (TMB) as a new quencher for preserving redox-labile disinfection byproducts and for quantifying free chlorine and free bromine
Authors: Lau Stephanie S. , Dias Ryan P. , Martin-Culet Kayla R. , Race Nicholas A. , Schammel Marella H. , Reber Keith P. , Roberts A. Lynn , Sivey John D.
Published: May 2018

1,3,5-Trimethoxybenzene can be used to quench residual chlorine and bromine without altering disinfection byproducts that are reactive toward traditional quenchers.
Biocatalytic approaches towards the stereoselective synthesis of vicinal amino alcohols
Authors: Gupta Pankaj , Mahajan Neha
Published: May 2018

The global need for clean manufacturing technologies and the management of hazardous chemicals and waste present new research challenges to both chemistry and biotechnology.
The effect of Reynolds number on TiO2 nanosponges doped with Li+ cations
Authors: Blasco-Tamarit Encarna , Muñoz-Portero María-José , Sánchez-Tovar Rita , Fernández-Domene Ramón Manuel , García-Antón José
Published: May 2018

TiO2 nanosponges and nanotubes were doped with Li+, which resulted in higher photocurrent densities, especially in nanosponges.
Design and synthesis of (aza)indolyl maleimide-based covalent inhibitors of glycogen synthase kinase 3β
Authors: Yang Zhimin , Liu Hui , Pan Botao , He Fengli , Pan Zhengying
Published: May 2018

The optimization of both non-covalent interactions and reactive groups led to azaindolyl maleimide compound38bas a selective and covalent inhibitor against GSK3β.
One-step CVD fabrication and optoelectronic properties of SnS2/SnS vertical heterostructures
Authors: Li Mingling , Zhu Yunsong , Li Taishen , Lin Yue , Cai Hongbing , Li Sijia , Ding Huaiyi , Pan Nan , Wang Xiaoping
Published: May 2018

A high-quality vertical SnS2/SnS heterostructure with excellent photoresponse has been fabricated and demonstrated.
Construction of a hierarchical NiFe layered double hydroxide with a 3D mesoporous structure as an advanced electrocatalyst for water oxidation
Authors: Yu Jiahao , Yang Fulin , Cheng Gongzhen , Luo Wei
Published: May 2018

A facile and cost-effective one-step hydrothermal method is used to synthesize NiFe LDH microclusters with a 3D hierarchically mesoporous architecture. This superior electrocatalyst can achieve a current density of 10 mA cm−2 with an ultralow overpotential of 211 mV toward the oxygen evolution reaction.
Simulation of osmotic energy conversion in nanoporous materials: a concise single-pore model
Authors: Xiao Feilong , Ji Danyan , Li Hao , Tang Jialiang , Feng Yaping , Ding Liping , Cao Liuxuan , Li Ning , Jiang Lei , Guo Wei
Published: May 2018

A concise single-pore model with a finite reservoir is sufficiently accurate to simulate osmotic energy conversion in nanoporous materials.
Assembly of fully substituted 2,5-dihydrothiophenes via a novel sequential multicomponent reaction
Authors: Mari Giacomo , Verboni Michele , De Crescentini Lucia , Favi Gianfranco , Santeusanio Stefania , Mantellini Fabio
Published: May 2018

A sequential multicomponent reaction between ketoesters, isothiocyanates and 1,2-diaza-1,3-dienes to create 2,5-dihydrothiophenes that can be converted into thiophenes.
Synthesis and optical properties of lead-free cesium germanium halide perovskite quantum rods
Authors: Chen Lin-Jer
Published: May 2018

Herein, the fabrication of a lead-free cesium germanium halide perovskite produced via a simple solvothermal process is reported for the first time.
Preparation of an octahedral PtNi/CNT catalyst and its application in high durability PEMFC cathodes
Authors: Wang Jue , Li Bing , Yang Daijun , Lv Hong , Zhang Cunman
Published: May 2018

The as-prepared octahedral PtNi/CNT catalyst exhibits enhanced ORR performance and single cell durability under high potential.
Molecular basis of rutin inhibition of protein disulfide isomerase (PDI) by combinedin silicoand experimental methods
Authors: Wang Xu , Xue Guangpu , Song Meiru , Xu Peng , Chen Dan , Yuan Cai , Lin Lin , Flaumenhaft Robert , Li Jinyu , Huang Mingdong
Published: May 2018

Rutin binds and inhibits PDI at b′x domain, H354 is one of the main binding sites.
Impact of bulky phenylalkyl substituents on the air-stable n-channel transistors of birhodanine analogues
Authors: Iijima Kodai , Le Gal Yann , Lorcy Dominique , Mori Takehiko
Published: May 2018

Performance and long-term air stability of birhodanine-based n-channel transistors are improved by introducing phenylethyl moieties.
Undergraduate chemistry students’ misconceptions about reaction coordinate diagrams
Authors: Lamichhane Roshan , Reck Cathrine , Maltese Adam V.
Published: May 2018

Misconceptions are the “the old, the bad, and the ugly” prior knowledge, ideas or conceptions that the learners have that hinder their further learning in science. Several types of misconceptions that undergraduate students hold about reaction coordinate diagrams (from here on we use the term “reaction coordinate diagrams” and “energy diagrams” interchangeably) are described herein. The rationale of 223 students were coded based on their responses to a multiple-choice question on the topic, and interviews (n = 10) were used to delve deeper into the students’ knowledge structures. The results of the open coding of the rationale and the interviews were used in developing an instrument which was administered to 57 students. In this paper, we present the assessment instrument and the alternate conceptions that students have regarding energy diagrams that have not been reported in the literature yet. Implications for instructional approaches particular to the energy diagram topic are discussed.
Correction: K2MnF6 as a precursor for saturated red fluoride phosphors: the struggle for structural stability
Authors: Verstraete Reinert , Sijbom Heleen F. , Korthout Katleen , Poelman Dirk , Detavernier Christophe , Smet Philippe F.
Published: May 2018

Correction for ‘K2MnF6 as a precursor for saturated red fluoride phosphors: the struggle for structural stability’ by Reinert Verstraete et al., J. Mater. Chem. C, 2017, 5, 10761–10769.
SINHCAF/FAM60A and SIN3A specifically repress HIF-2α expression
Authors: Biddlestone John , Batie Michael , Bandarra Daniel , Munoz Ivan , Rocha Sonia
Published: May 2018

The SIN3A–HDAC (histone deacetylase) complex is a master transcriptional repressor, required for development but often deregulated in disease. Here, we report that the recently identified new component of this complex, SINHCAF (SIN3A and HDAC-associated factor)/FAM60A (family of homology 60A), links the SIN3A–HDAC co-repressor complex function to the hypoxia response. We show that SINHCAF specifically represses HIF-2α mRNA and protein expression, via its interaction with the transcription factor SP1 (specificity protein 1) and recruitment of HDAC1 to the HIF-2α promoter. SINHCAF control over HIF-2α results in functional cellular changes in in vitro angiogenesis and viability. Our analysis reveals an unexpected link between SINHCAF and the regulation of the hypoxia response.
Latest developments in MUC1 immunotherapy
Authors: Taylor-Papadimitriou Joyce , Burchell Joy M. , Graham Rosalind , Beatson Richard
Published: May 2018

Currently, there is renewed interest in attempting to recruit the host immune system to eliminate cancers, and within this renewed activity, MUC1 continues to arouse interest. MUC1 has been considered a possible therapeutic target for the past 30 years as it is up-regulated, aberrantly glycosylated and its polarization is lost in many adenocarcinomas. Moreover, MUC1 is expressed by some haematopoietic cancers, including acute myeloid leukaemia and myeloma. Although multiple clinical trials have been initiated and immune responses have been documented, effective clinical benefit worthy of approval for general application has not as yet been achieved. However, this does not appear to have quelled the interest in MUC1 as a therapeutic target, as shown by the increase in the number of MUC1-based clinical trials initiated in 2017 (Figure 1). As with all translational studies, incorporating new relevant research findings into therapeutic strategy is difficult. Decisions are made to commit to a specific strategy based on the information and data available when the trial is initiated. However, the time required for preclinical studies and early trials can render the founding concept not always appropriate for proceeding to a larger definitive trial. Here, we summarize the attempts made, to date, to bring MUC1 into the world of cancer immunotherapy and discuss how research findings regarding MUC1 structure and function together with expanded knowledge of its interactions with the tumour environment and immune effector cells could lead to improved therapeutic approaches.Figure 1.Number of MUC1-targeted trials initiated each year.
Non-coding RNAs and exercise: pathophysiological role and clinical application in the cardiovascular system
Authors: Gomes Clarissa P.C. , de Gonzalo-Calvo David , Toro Rocio , Fernandes Tiago , Theisen Daniel , Wang Da-Zhi , Devaux Yvan ,   on behalf of the Cardiolinc™ network
Published: May 2018

There is overwhelming evidence that regular exercise training is protective against cardiovascular disease (CVD), the main cause of death worldwide. Despite the benefits of exercise, the intricacies of their underlying molecular mechanisms remain largely unknown. Non-coding RNAs (ncRNAs) have been recognized as a major regulatory network governing gene expression in several physiological processes and appeared as pivotal modulators in a myriad of cardiovascular processes under physiological and pathological conditions. However, little is known about ncRNA expression and role in response to exercise. Revealing the molecular components and mechanisms of the link between exercise and health outcomes will catalyse discoveries of new biomarkers and therapeutic targets. Here we review the current understanding of the ncRNA role in exercise-induced adaptations focused on the cardiovascular system and address their potential role in clinical applications for CVD. Finally, considerations and perspectives for future studies will be proposed.
The neutrophil-mobilizing cytokine interleukin-26 in the airways of long-term tobacco smokers
Authors: Che Karlhans Fru , Tufvesson Ellen , Tengvall Sara , Lappi-Blanco Elisa , Kaarteenaho Riitta , Levänen Bettina , Ekberg Marie , Brauner Annelie , Wheelock Åsa M. , Bjermer Leif , Sköld C. Magnus , Lindén Anders
Published: May 2018

Long-term tobacco smokers with chronic obstructive pulmonary disease (COPD) or chronic bronchitis display an excessive accumulation of neutrophils in the airways; an inflammation that responds poorly to established therapy. Thus, there is a need to identify new molecular targets for the development of effective therapy. Here, we hypothesized that the neutrophil-mobilizing cytokine interleukin (IL)-26 (IL-26) is involved in airway inflammation amongst long-term tobacco smokers with or without COPD, chronic bronchitis or colonization by pathogenic bacteria. By analyzing bronchoalveolar lavage (BAL), bronchail wash (BW) and induced sputum (IS) samples, we found increased extracellular IL-26 protein in the airways of long-term smokers in vivo without further increase amongst those with clinically stable COPD. In human alveolar macrophages (AM) in vitro, the exposure to water-soluble tobacco smoke components (WTC) enhanced IL-26 gene and protein. In this cell model, the same exposure increased gene expression of the IL-26 receptor complex (IL10R2 and IL20R1) and nuclear factor κ B (NF-κB); a proven regulator of IL-26 production. In the same cell model, recombinant human IL-26 in vitro caused a concentration-dependent increase in the gene expression of NF-κB and several pro-inflammatory cytokines. In the long-term smokers, we also observed that extracellular IL-26 protein in BAL samples correlates with measures of lung function, tobacco load, and several markers of neutrophil accumulation. Extracellular IL-26 was further increased in long-term smokers with exacerbations of COPD (IS samples), with chronic bronchitis (BAL samples ) or with colonization by pathogenic bacteria (IS and BW samples). Thus, IL-26 in the airways emerges as a promising target for improving the understanding of the pathogenic mechanisms behind several pulmonary morbidities in long-term tobacco smokers.
Quantitative spectral classification of Galactic O stars
Authors: Martins F.
Published: May 2018

Our goal is to provide a quantification of several spectral classification criteria for O stars. We collect high-spectral resolution spectra of 105 Galactic O-type stars from various archives. We measured equivalent widths of classification lines. We defined average values of classification criteria for given spectral types and luminosity classes. We find that the ratio He I 4471 to He II 4542 well matches the published ratios for spectral types. We have quantified equivalent width ratios of helium and silicon lines among O8–O9.7 stars to refine spectral class typing in this spectral range. We present quantitative criteria to separate between luminosity class V, IV–III–II (grouped), and I among O3–O8.5 stars, mainly based on the strength of He II 4686. We find that these criteria also define very well the f, (f), and ((f)) classes for O3–O7.5 stars. Among O9–O9.7 stars we quantify the ratios of He II 4686 to He I 4713 and Si IV 4089 to He I 4026 for all luminosity classes. The tabulated values of the classification criteria should help classify any new O-type stars. The final step of the classification process should rely on a direct comparison to standard stars of the assigned spectral type or luminosity class.
Control and stabilization of the periodic fifth order Korteweg-de Vries equation
Authors: Flores Cynthia , Smith Derek L.
Published: May 2018

We establish local exact control and local exponential stability of periodic solutions of fifth order Korteweg-de Vries type equations in Hs(𝕋),s> 2. A dissipative term is incorporated into the control which, along with a propagation of regularity property, yields a smoothing effect permitting the application of the contraction principle.
A theory on the role of π-electrons of docosahexaenoic acid in brain function
Authors: Crawford MA , Thabet M , Wang Y , Broadhurst CL , Schmidt WF
Published: May 2018

Background: Docosahexaenoic acid (DHA) has been the dominant acyl component of the membrane phosphoglycerides in neural signaling systems since the origin of the eukaryotes. In this paper, we propose, this extreme conservation, is explained by its special electrical properties. Based on the Pauli Exclusion Principle we offer an explanation on how its six methylene interrupted double-bonds provide a special arrangement of π-electrons that offer an absolute control for the precision of the energy of the signal. Precision is not explained by standard concepts of ion movement or synaptic strengthening by enhanced protein synthesis. Yet precision is essential to visual acuity, truthful recall and the exercise of a dedicated neural pathway. Concept: Synaptic membranes have been shown to actively incorporate DHA with a high degree of selectivity. During a learning process, this biomagnification will increase the proportion of membrane DHA with two consequential neuronal and synaptic enhancements which build into a David Marr type model of the real world: DHA induced gene expression resulting in enhanced protein synthesis; increased density of π-electrons which could provide memory blocks and provide for the preferential flow of a current in neural pathways. Proposal: Both the above imply memory from synaptic strengthening. We propose memory is achieved by the activation of neuronal synaptic activation with synaptic turnover resulting in enhanced membrane DHA, which in turn induces gene expression, protein synthesis and π-electron density. Repetition amplifies the process activating synapses, which form a matrix representing the memory. The electro-chemical potentials then fire the electrons as electromagnetic waves via the six methylene interrupted double bonds. These allow transmission at a specific energy level based on their quantum mechanical properties providing the precision required for faithful recall. It is difficult to conceive of protein synthesis alone providing for precision. Using the principle of the dual properties of photons and electrons we develop the idea of complex wave patterns representing the visual or auditory fields. These are likely to be non-computable. We suggest that harmonization of the electromagnetic waves can result in cohesion explaining recall and associations. The cohesion of electromagnetic flow leads to a surge above the resting level, which is recognized by the brain as, demonstrated in artificial, electrical stimulus during neurosurgery.
Effect of 4-Hydroxy-2,3-trans-nonenal on Platelet Function
Authors: Selley Michael L , McGuiness Julie A , Jenkin Lynn A , Bartlett Mark R , Ardlie Neville G
Published: May 2018

4-Hydroxy-2,3-trans-nonenal (HNE), an aldehyde end-product of lipid peroxidation, potentiated aggregation and increased thromboxane A2 formation in platelets challenged with ADP, thrombin or the ionophore A23187. These effects were observed at HNE concentrations in the range 10-100 μM. Platelet responses to collagen, epinephrine and arachidonic acid were not affected by PINE. Concentrations of HNE in excess of 100 pM inhibited platelet activation. HNE increased the release of 3H-arachidonic acid from prelabelled platelet phospholipids in response to thrombin or ADR It is proposed that HNE may play an important role in controlling platelet function by regulating the activity of phospholipase A2.
Clinical Experience with a Pasteurised Human Plasma Concentrate in Factor XIII Deficiency
Authors: Daly Helena M , Haddon M E
Published: May 2018

A three-day-old infant presented with umbilical haemorrhage. Factor XIII deficiency was diagnosed. When one month old she commenced prophylactic injections of pasteurised factor XIII concentrate of human plasma origin. During two and a half years treatment there were no haemorrhagic episodes and factor XIII concentrate was well tolerated. Satisfactory post infusion factor XIII levels were achieved. Three transient elevations of aspartate transaminase occurred, the cause of which has not been established. There was no evidence of transmission of hepatitis or H.I.V. infection. A brother, born one year later, is also affected and commenced prophylactic therapy with the same factor XIII concentrate. Experience in these two infants suggests the product is efficacious.
Potentiation by Adrenaline of Ca2+ Influx and Mobilization in Stimulated Human Platelets: Dissociation from Thromboxane Generation and Aggregation
Authors: Powling M J , Hardisty R M
Published: May 2018

In a medium containing 1 mM extracellular Ca2+ (Ca2+o), the prior addition of 0.5 pM adrenaline to quin 2-loaded human platelets increased both the rate and amplitude of the rise in cytosolic free Ca2+ (Ca2+i) in response to sub-threshold concentrations of thrombin and PAF and these effects were not prevented by blocking either fibrinogen binding and aggregation or cyclo-oxygenase. In the presence of 2 mM EGTA ([Ca2+o] >100 nM), the rate, but not the extent of rise of [Ca2+i] was enhanced by adrenaline, and this was also unaffected by blockade of cyclo-oxygenase. Addition of adrenaline 1 min after the other agonist in the presence of 1 mM Ca2+o resulted in aggregation without further elevation of [Ca2+i]. Adrenaline thus enhances both influx and intracellular mobilization of Ca2+ by a mechanism independent of both fibrinogen binding and thromboxane production, but these effects do not fully explain its potentiation of aggregation by other agonists
Monocytes of Patients Congenitally Deficient in Plasma Factor XIII Lack Factor XIII Subunit A Antigen and Transglutaminase Activity
Authors: Muszbek László , Ádány Roza , Kávai Mária , Boda Zoltán , Lopaciuk Stanislaw
Published: May 2018

Monocytes isolated from patients with severe deficiency in plasma Factor XIII of blood coagulation (FXIII) were tested for FXIII antigen and transglutaminase activity. By immunoperoxi- dase method the patients’ monocytes, in contrast to normal controls, showed no reaction with a monospecific antibody against FXIII subunit ª.This result was confirmed by immuno- blotting technique, as well. In addition, tissue macrophages tested in one of the patients were also exempt of FXIII subunit ª antigen. The transglutaminase activity in FXIII deficient monocytes was below the limit of the detection of the dansylcadaverine incorporation assay. The results suggest that FXIII subunitªof monocytes/macrophages and its plasma and platelet counterparts are closely related or identical proteins and demonstrate that the transglutaminase activity in monocytes is of FXIII origin and tissue transglutaminase is present, if at all, only in insignificant amount.
Low Molecular Weight Heparin in Haemodialysis for Chronic Renal Failure: Dose Finding Study of CY222
Authors: Ireland H , Lane D A , Flynn A , Pegrum A C , Curtis J R
Published: May 2018

A dose finding study of the very low molecular weight heparin CY222 (MW 2500) in patients (n = 8) with chronic renal failure undergoing dialysis has been carried out to (i) establish an effective dose and (ii) determine the relationship between ex vivo anti-factor Xa levels in plasma and the anticoagulant effect (in vivo suppression of FPA levels). Doses of CY222 were compared to a dose (5000 iu bolus + 1500 iu/hr) of unfractionated heparin (UFH) that has been shown to suppress FPA levels during prolonged (>5 hr) dialysis (Ireland et ah, J Lab Clin Med 103, 643, 1984). CY222 given iv in increasing doses produced a dose related increase in anti-factor Xa levels (measured as Institute Choay u/ml, with CY222 itself as standard) and suppression of FPA levels. When given in its highest dose, 20,000 Institute Choay u bolus + 1500 Institute Choay u/hr, there was little effect upon KCCT, FPA levels were statistically indistinguishable from those of the UFH regime (indicating comparable anticoagulant effect), but anti-factor Xa levels (expressed in Institute Choay u/ ml) were 2-3 times those of UFH (expressed in iu/ml). All samples were also assayed for anti-factor Xa level against the proposed low MW Heparin Standard. Plasma levels of CY222 were then found to be 2.78 times lower, so that the anti-factor Xa levels of CY222 required to produce comparable anticoagulant effect were then indistinguishable from those of UFH. Clinically, doses of CY222 exceeding 10,000 Institute Choay u bolus were effective, although increasing amounts of fibrin were visible in the drip chamber of the dialyser circuit with decreasing dose. These results indicate that CY222 is an effective anticoagulant for haemodialysis that can be monitored by its anti-factor Xa level in plasma (in conjunction with the appropriate standard). For prolonged dialysis a dose of 20,000 Institute Choay u bolus + 1500 Institute Choay u/hr is effective at suppressing fibrin formation, while the maintenance infusion may be unnecessary for short frequent dialyses.
The Application of the Biotin/Avidin System to the von Willebrand Factor Antigen Immunoassay
Authors: Taylor L D
Published: May 2018

A vWf: Ag ELISA which uses biotinylated anti-vWf: Ag IgG and an avidin/biotinylated peroxidase (ABP) complex detection system has been developed. The sensitivity of the ELISA for vWf: Ag was 4 × 10-5 U/ml which is approximately 10-fold lower than previously reported vWf: Ag ELISA’s. The avidin used for the preparation of the ABP complex was glutaraldehyde-treated. This treatment increased the reactivity 2-3-fold as compared to ABP complex prepared using untreated avidin. The reactivity of two commercial detection reagents was also tested.

The effect of the reduction of the total assay time to 3.5 h is also described. In this form the detection limit for vWf: Ag was 2 × 10-4 U/ml, the intra-assay precision at vWf: Ag concentrations of 0.01 and 0.0025 U/ml was 3.8% and 4.9% respectively and ELISA results for normal individuals still correlated well with those obtained using electro-immunodiffusion (r = 0.93).
Pharmacokinetics of Dermatan Sulfate in the Rabbit After Intravenous Injection
Authors: Dol F , Houin G , Dupouy D , Cadroy Y , Caranobe C , Gabaig A M , Mardiguian J , Sie P , Boneu B
Published: May 2018

To investigate the pharmacokinetic properties of dermatan sulfate (DS), a new potential antithrombotic agent, two different approaches were used. In the first one, DS was derivatized with 3-4 hydroxyphenyl propionic acid N hydroxysuccinimide ester (SHPP) and iodinated. The labelled derivative was injected by IV route to rabbits with increasing doses of unlabelled compound ranging from 20 to 4000 μg/kg. The disappearance of DS from plasma was characterized by measuring both the circulating radioactivity and the biological activity using an original assay based upon the catalysis of heparin cofactor II – thrombin formation. The radioactivity data indicated that the volume of distribution, the clearance and the half life of the tracer were independent of the dose of DS injected. DS concentrations measured by the bioassay indicated that more than 90% were cleared with half lives close to those calculated from the radioactivity data; the remaining biological activity was cleared at a slower rate. Experiments performed with bi-nephrectomized animals indicated that the kidneys play a major role in the elimination of DS or of its metabolites which may have a residual biological activity. In the second set of experiments, unlabelled DS was delivered under continuous intravenous infusion for 5 hours at 5 increasing doses ranging from 160 to 4200 μg/kg/h. The biological activities were used to measure the plateau concentration of DS: there was a linear relationship between the dose delivered and the plasma concentration. These data indicate that the pharmacokinetic profile of DS is very close to that of low molecular weight heparin, and quite different from that of SH.
Cytomegalovirus Alters the von Willebrand Factor Content in Human Endothelial Cells
Authors: Bruggeman C A , Debie W H M , Muller A D , Schutte B , Dam-Mieras M CE van
Published: May 2018

Cultured human endothelial cells were infected with human cytomegalovirus AD 169 and Kerr. The infection resulted in the appearance of viral antigens in the nuclei of about 10% of the endothelial cells and in the concomittant disappearance of vWF from the infected cells. No differences were observed between endothelial cells from different sources (umbilical cord veins or arteries, adult veins).
Standard Heparin Enhances the Antithrombotic Activity of Dermatan Sulfate in the Rabbit but CY 216 Does Not
Authors: Cadroy Y , Dol F , Caranobe C , Petitou M , Lormeau J C , Sié P , Choay J , Boneu B
Published: May 2018

Standard heparin (SH) and dermatan sulfate (DS) two gly- cosaminoglycans with different pharmacological targets are effective antithrombotic agents in the rabbit. We have investigated the antithrombotic activity of the association DS plus SH. It was found that doses as low as 25 µg/kg for DS and 10 µg/kg for SH were ineffective when injected separately but generated a high and significant antithrombotic activity when injected together. These results were confirmed when higher doses of each compound were delivered in association. Further experiments were performed to determine if the enhancement of the antithrombotic activity of DS by HS resulted from its anti-factor Ha or antifactor Xa activity or from its moiety without affinity to AT III. A low molecular weight heparin (CY 216) with an anti-factor Xa/ anti-factor Ha ratio of 5, the synthetic pentasaccharide bearing the minimum binding sequence to antithrombin III, and a low affinity fraction of SH to AT III did not increase the antithrombotic activity of DS; in contrast a high affinity fraction of SH to AT III had the same effect than SH. We conclude that the enhancement of the antithrombotic activity of DS by SH mainly results from its anti-factor IIa activity.
Fibrinolysis in Normal Subjects - Comparison Between Plasminogen Activator Inhibitor and Other Components of the Fibrinolytic System
Authors: Nicoloso Grazia , Hauert Jacques , Kruithof Egbert K O , Melle Guy Van , Bachmann Fedor
Published: May 2018

We analyzed fibrinolytic parameters in 20 healthy men and 20 healthy women, aged from 25 to 59, before and after 10 and 20 min venous occlusion. The 10 min post-occlusion fibrinolytic activity measured directly in diluted unfractionated plasma by a highly sensitive 125I-fibrin plate assay correlated well with the activity of euglobulins determined by the classical fibrin plate assay (r = 0.729), but pre-stasis activities determined with these two methods did not correlate (r = 0.084). The enhancement of fibrinolytic activity after venous occlusion was mainly due to an increase of t-PA in the occluded vessels (4-fold increase t-PA antigen after 10 min and 8-fold after 20 min venous occlusion). Plasminogen activator inhibitor (PAI) activity and plasminogen activator inhibitor 1 (PAI-1)1 antigen levels at rest showed considerable dispersion ranging from 1.9 to 12.4 U/ml, respectively 6.9 to 77 ng/ml. A significant increase of PAI-1 antigen levels was observed after 10 and 20 min venous occlusion. At rest no correlation was found between PAI activity or PAI-1 antigen levels and the fibrinolytic activity measured by 125I-FPA. However, a high level of PAI-1 at rest was associated with a high prestasis antigen level of t-PA and a low fibrinolytic response after 10 min of venous stasis. Since the fibrinolytic response inversely correlated with PAI activity at rest, we conclude that its degree depends mainly on the presence of free PAI.
Comparison of the Platelet Aggregation Induced by Three Thrombin-Like Enzymes of Snake Venoms and Thrombin
Authors: Teng Che-Ming , Ko Feng-Nien
Published: May 2018

Platelet aggregation induced by three thrombin-like enzymes of snake venoms was compared with that by thrombin. Acutin was isolated from Agkistrodon acutus venom and thrombocytin and batroxobin were from Bothrops atrox venom. The fibrinogenclotting activities were 700,170 and 7 U/mg for batroxobin, acutin and thrombocytin, respectively. They induced aggregation and ATP release of washed rabbit platelets. The aggregating activity of thrombin was 102, 104 and 105 times more potent than those of thrombocytin, acutin and batroxobin, respectively. Plateletactivating potency of the thrombin-like enzymes was correlated with their effectiveness on the retractility and elasticity of the clots. Platelet aggregation induced by thrombin or thrombocytin could be inhibited by heparin with antithrombin III while that by acutin or batroxobin could not. Indomethacin showed weak inhibition on the aggregation while the ADP-scavenging system, creatine phosphate/creatine phosphokinase, inhibited the aggregation induced by the three thrombin-like enzymes but not that by thrombin. Platelet aggregation induced by the thrombin-like enzymes could not be inhibited by PAF antagonists-BN 52021, kadsurenone or L-652,731. In the presence of EGTA, only thrombin could induce ATP release from platelets. Thrombin-like enzymes and low concentration of thrombin did not form thromboxane B2. Nitroprusside and prostaglandin E1 completely inhibited the aggregation, mepacrine and imipramine showed marked inhibition while verapamil had only weak inhibition. It is concluded that the aggregation induced by the thrombin-like enzymes is different from that of thrombin and mainly due to ADP released from platelets.
A Monoclonal Antibody-Based Enzyme Immunoassay for Fibrin Degradation Products in Plasma
Authors: Koppert P W , Hoegee-de Nobel E , Nieuwenhuizen W
Published: May 2018

We have developed a sandwich-type enzyme immunoassay (EIA) for the quantitation of fibrin degradation products (FbDP) in plasma with a time-to-result of only 45 minutes.* The assay is based on the combination of the specificities of two monoclonal antibodies (FDP-14 and DD-13), developed in our institute. FDP-14, the capture antibody, binds both fibrinogen degradation products (FbgDP) and FbDP, but does not react with the parent fibrin(ogen) molecules. It has its epitope in the E-domain of the fibrinogen molecule on the Bβ-chain between amino acids 54-118. Antibody DD-13 was raised using D-dimer as antigen and is used as a tagging antibody, conjugated with horse-radish peroxidase. A strong positive reaction is obtained with a whole blood clot lysate (lysis induced by tissue-type plasminogen activator) which is used as a standard. The EIA does virtually not detect FbgDP i. e. purified fragments X, Y, or FbgDP generated in vitro in plasma by streptokinase treatment. This indicates that the assay is specific for fibrin degradation products.

We have successfully applied this assay to the plasma of patients with a variety of diseased states. In combination with the assay previously developed by us for FbgDP and for the total amount of FbgDP + FbDP (TDP) in plasma, we are now able to study the composition of TDP in patients plasma in terms of FbgDP and FbDP.
Mid-Term Clinical Outcome and Reconstruction of Posterior Tibial Slope after UKA
Authors: Franz Alois , Boese Christoph , Matthies Andrej , Leffler Jörg , Ries Christian
Published: May 2018

Unicompartmental knee arthroplasty (UKA) has gained growing popularity over the last decades. The posterior tibial slope (PTS) has been shown to play a significant role for knee biomechanics and is thought to be crucial for clinical function of the UKA. We evaluated the clinical outcome at mid-term follow-up after UKA. Furthermore, the reconstruction of the individual PTS was analyzed. A total of 91 consecutive patients undergoing medial UKA for osteoarthritis were included. Patients were contacted by telephone for a survival analysis at a minimum of 30 months after surgery. Patient-oriented questionnaires and Knee Osteoarthritis Outcome Score (KOOS) were obtained. A retrospective chart review and radiological analysis of component alignment were performed for all patients before and at 6 weeks after surgery. Of 91 patients (93 knees) undergoing UKA, 69 patients (70 knees) were available for clinical follow-up after a mean of 56.0 (range 31–81) months post-surgery. The clinical results of the examined patients in the present study showed mean subscale scores of the KOOS and Western Ontario and McMaster Universities Osteoarthritis Index between 71 and 91%. Overall 7 of 91 patients were revised during the course of follow-up period and underwent total knee arthroplasty. A Kaplan–Meier analysis showed a survival rate for UKA of 90.5% after 48 months. Calculated implant survival was 75.9 months (95% confidence interval 72.3–79.6) at the mean. The radiographic analysis of pre- and postoperative PTS showed no differences (p = 0.113).UKA for osteoarthritis of the medial knee compartment shows encouraging clinical results at mid-term follow-up. The individual PTS could be reconstructed within acceptable ranges. This is a retrospective therapeutic study with Level IV.
Prevotella melaninogenica Meningitis and Abscess: A Complication of the Removal of a Midline Dermoid Cyst
Authors: Garcia Megan B. , Kunz Anjali N.
Published: May 2018

Prevotella species are gram-negative anaerobic commensal bacteria of the oropharynx, which frequently cause periodontal disease but are otherwise rarely implicated in serious bacterial infections. Cranial dermoid cysts are benign neoplasms that grow along the planes of the embryonic neural tube closure. In infants, they most commonly present in frontal locations, including periorbital, nasal, and within the anterior fontanelle. Although dermoid cysts are slow growing, usually uncomplicated, and easily treated definitively with surgical excision, cranial cysts located on the midline are associated with a higher risk for persistent dermal sinus tract with intracranial extension of the tumor. We describe a case of a 10-month-old male patient with an occipital midline dermoid cyst with intracranial extension, infected with Prevotella melaninogenica, and complicated by intracranial abscess formation and meningitis.

This case highlights two unusual disease entities: the uncommon occipital location of a dermoid cyst, and complications of that cyst caused by a serious bacterial infection with a normal oral flora. We discuss the recommendation for neuroimaging prior to surgical excision of a midline dermoid cyst, given the risk for dermal sinus tract with intracranial communication. We also discuss potential mechanisms for bacterial inoculation of this cyst with Prevotella melaninogenica. This pathogen has not previously been reported as a complication of dermoid cysts.
An 18-ps TDC using timing adjustment and bin realignment methods in a Cyclone-IV FPGA
Authors: Cao Guiping , Xia Haojie , Dong Ning
Published: May 2018

The method commonly used to produce a field-programmable gate array (FPGA)-based time-to-digital converter (TDC) creates a tapped delay line (TDL) for time interpolation to yield high time precision. We conduct timing adjustment and bin realignment to implement a TDC in the Altera Cyclone-IV FPGA. The former tunes the carry look-up table (LUT) cell delay by changing the LUT’s function through low-level primitives according to timing analysis results, while the latter realigns bins according to the timing result obtained by timing adjustment so as to create a uniform TDL with bins of equivalent width. The differential nonlinearity and time resolution can be improved by realigning the bins. After calibration, the TDC has a 18 ps root-mean-square timing resolution and a 45 ps least-significant bit resolution.
Interaction of an electron with coherent dipole radiation: Role of convergence and anti-dephasing
Authors: Robinson A. P. L. , Arefiev A. V.
Published: May 2018

The impact of longitudinal electric fields that are present in intense focusing and defocusing electromagnetic pulses on electron acceleration is investigated. These fields are typically much weaker than the transverse fields, but it is shown that they can have a profound effect on electron energy gain. It is shown that the longitudinal electric field of a defocusing pulse is directed backward along the trajectory of an accelerated electron, which leads to a continuous net energy gain. At the same time, the effect of the transverse oscillating electric field in a defocusing pulse is to reduce the electron energy over multiple oscillations. In contrast to a well-known interaction with a plane wave, the electron is able to retain a substantial amount of energy following its interaction with a defocusing pulse. The roles of the transverse and longitudinal electric fields are reversed in a focusing pulse, which leads to a reduction in the energy retention. The present analysis underscores the importance of relatively weak oscillating electric fields in focusing and defocusing pulses.
A multimodal and multidirectional vibrational energy harvester using a double-branched beam
Authors: Deng Huaxia , Du Yu , Wang Zhemin , Zhang Jin , Ma Mengchao , Zhong Xiang
Published: May 2018

Vibrational energy harvesters, which are generally based on a single cantilever beam, are mainly effective for excitations perpendicular to the beam. However, typical ambient vibrations are of multifrequency and are multidirectional. To achieve full harvesting of multifrequency vibrational energy in multiple directions, this letter proposes a multidirectional vibrational energy harvester utilizing multimodal vibrations of a double-branched beam that has four natural frequencies below 22 Hz. Comparison experiments in different directions demonstrate an improvement of energy harvesting when this double-branched beam is used. Under horizontal excitation, the maximum open-circuit voltage is increased to 1845%. Under vertical excitation, the average power density is increased over 3800 times. The experimental results indicate that this structural design significantly improves the energy collection efficiency in both horizontal and vertical directions, even with a lighter structural weight.
Non-linear instability analysis of the two-dimensional Navier-Stokes equation: The Taylor-Green vortex problem
Authors: Sengupta Tapan K. , Sharma Nidhi , Sengupta Aditi
Published: May 2018

An enstrophy-based non-linear instability analysis of the Navier-Stokes equation for two-dimensional (2D) flows is presented here, using the Taylor-Green vortex (TGV) problem as an example. This problem admits a time-dependent analytical solution as the base flow, whose instability is traced here. The numerical study of the evolution of the Taylor-Green vortices shows that the flow becomes turbulent, but an explanation for this transition has not been advanced so far. The deviation of the numerical solution from the analytical solution is studied here using a high accuracy compact scheme on a non-uniform grid (NUC6), with the fourth-order Runge-Kutta method. The stream function-vorticity (ψ, ω) formulation of the governing equations is solved here in a periodic square domain with four vortices at t = 0. Simulations performed at different Reynolds numbers reveal that numerical errors in computations induce a breakdown of symmetry and simultaneous fragmentation of vortices. It is shown that the actual physical instability is triggered by the growth of disturbances and is explained by the evolution of disturbance mechanical energy and enstrophy. The disturbance evolution equations have been traced by looking at (a) disturbance mechanical energy of the Navier-Stokes equation, as described in the work of Sengupta et al., “Vortex-induced instability of an incompressible wall-bounded shear layer,” J. Fluid Mech. 493, 277–286 (2003), and (b) the creation of rotationality via the enstrophy transport equation in the work of Sengupta et al., “Diffusion in inhomogeneous flows: Unique equilibrium state in an internal flow,” Comput. Fluids 88, 440–451 (2013).