bluuebunny/crossref_metadata_2025 huggingface dataset:
Imaging Dose, Cancer Risk and Cost Analysis in Image-guided Radiotherapy of Cancers
Authors: Zhou Li , Bai Sen , Zhang Yibao , Ming Xin , Zhang Ying , Deng Jun
Published: June 2018

The purpose of this retrospective study is to evaluate the cumulative imaging doses, the associated cancer risk and the cost related to the various radiological imaging procedures in image-guided radiotherapy of cancers. Correlations between patients’ size and Monte Carlo simulated organ doses were established and validated for various imaging procedures, and then used for patient-specific organ dose estimation of 4,832 cancer patients. The associated cancer risk was estimated with published models and the cost was calculated based on the standard billing codes. The average (range) cumulative imaging doses to the brain, lungs and red bone marrow were 38.0 (0.5–177.3), 18.8 (0.4–246.5), and 49.1 (0.4–274.4) cGy, respectively. The associated average (range) lifetime attributable risk of cancer incidence per 100,000 persons was 78 (0–2798), 271 (1–8948), and 510 (0–4487) for brain cancer, lung cancer and leukemia, respectively. The median (range) imaging cost was $5256 (4268–15896) for the head scans, $5180 (4268–16274) for the thorax scans, and $7080 (4268–15288) for the pelvic scans, respectively. The image-guidance procedures and the accumulated imaging doses should be incorporated into clinical decision-making to personalize radiotherapy for individual patients.
Unraveling the Mesoscale Evolution of Microstructure during Supersonic Impact of Aluminum Powder Particles
Authors: Suresh Sumit , Lee Seok-Woo , Aindow Mark , Brody Harold D. , Champagne Victor K. , Dongare Avinash M.
Published: June 2018

A critical challenge in the predictive capability of materials deformation behavior under extreme environments is the availability of computational methods to model the microstructural evolution at the mesoscale. The capability of the recently-developed quasi-coarse-grained dynamics (QCGD) method to model mesoscale behavior is demonstrated for the phenomenon of supersonic impact of 20 µm sized Al particles on to an Al substrate at various impact velocities and over time and length scales relevant to cold spray deposition. The QCGD simulations are able to model the kinetics related to heat generation and dissipation, and the pressure evolution and propagation, during single particle impact over the time and length scales that are important experimentally. These simulations are able to unravel the roles of particle and substrate deformation behavior that lead to an outward/upward flow of both the particle and the substrate, which is a likely precursor for the experimentally observed jetting and bonding of the particles during cold spray impact.
Single Walled BiI3 Nanotubes Encapsulated within Carbon Nanotubes
Authors: Ashokkumar Anumol Erumpukuthickal , Enyashin Andrey N. , Deepak Francis Leonard
Published: June 2018

Inorganic nanotubes are morphological counterparts of carbon nanotubes (CNTs). Yet, only graphene-like BN layer has been readily organized into single walled nanotubes so far. In this study, we present a simple route to obtain inorganic single walled nanotubes - a novel ultrathin morphology for bismuth iodide (BiI3), embedded within CNTs. The synthesis involves the capillary filling of BiI3into CNT, which acts as a nanotemplate, by annealing the BiI3-CNT mixture above the melting point of BiI3. Aberration corrected scanning/transmission electron microscopy is used in characterizing the novel morphology of BiI3. A critical diameter which enables the formation of BiI3nanotubes, against BiI3nanorods is identified. The relative stability of these phases is investigated with the density functional theory calculations. Remarkably, the calculations reveal that the single walled BiI3nanotubes are semiconductors with a direct band gap, which remain stable even without the host CNTs.
Mito-TEMPO improves development competence by reducing superoxide in preimplantation porcine embryos
Authors: Yang Seul-Gi , Park Hyo-Jin , Kim Jin-Woo , Jung Jae-Min , Kim Min-Ji , Jegal Ho-Guen , Kim In-Su , Kang Man-Jong , Wee Gabbine , Yang Hee-Young , Lee Yun-Han , Seo Ji-Hae , Kim Sun-Uk , Koo Deog-Bon
Published: June 2018

Mito-TEMPO is a well-known mitochondria-specific superoxide scavenger. However, the effect of Mito-TEMPO on porcine embryo development, to our knowledge, has not been studied yet. In the present study, porcine embryos were classified into two groups (G1 and G2) based on the cytoplasm lipid contents at the zygote stage. The development of blastocysts derived from G2 zygotes was reduced (G2:16.2 ± 7.9% vs G1: 26.5 ± 5.9%; 1.6-fold, p < 0.05) compared to those from G1 zygotes. In G2 embryos, the proportion of TUNEL-positive cells was also higher than that of G1 embryos. Superoxide in G2 embryos was significantly increased compared to that in G1 embryos. Mitochondrial membrane potential and ATP production were lower in G2 embryos than in G1 embryos. Phosphorylation of Drp1 at Ser 616 increased in G1 embryos during the cleavage stages compared to that in the zygote but was not significantly different in G2 embryos. Then, the effects of Mito-TEMPO were investigated in G2 embryos. Blastocyst formation rate (G2: 19.1 ± 5.1% vs G2 + Mito-TEMPO: 28.8 ± 4.0%; 1.5-fold, p < 0.05) and mitochondrial aggregation were recovered after superoxide reduction by Mito-TEMPO treatment. Thus, we showed that Mito-TEMPO improves blastocyst development by superoxide reduction in porcine embryos in vitro.
Analysis of the Gut Microbiome of Rural and Urban Healthy Indians Living in Sea Level and High Altitude Areas
Authors: Das Bhabatosh , Ghosh Tarini Shankar , Kedia Saurabh , Rampal Ritika , Saxena Shruti , Bag Satyabrata , Mitra Ridhima , Dayal Mayanka , Mehta Ojasvi , Surendranath A. , Travis Simon P. L. , Tripathi Prabhanshu , Nair G. Balakrish , Ahuja Vineet
Published: June 2018

The diversity and basic functional attributes of the gut microbiome of healthy Indians is not well understood. This study investigated the gut microbiome of three Indian communities: individuals residing in rural and urban (n = 49) sea level Ballabhgarh areas and in rural high altitude areas of Leh, Ladakh in North India (n = 35). Our study revealed that the gut microbiome of Indian communities is dominated by Firmicutes followed by Bacteroidetes, Actinobateria and Proteobacteria. Although, 54 core bacterial genera were detected across the three distinct communities, the gut bacterial composition displayed specific signatures and was observed to be influenced by the topographical location and dietary intake of the individuals. The gut microbiome of individuals living in Leh was observed to be significantly similar with a high representation of Bacteroidetes and low abundance of Proteobacteria. In contrast, the gut microbiome of individuals living in Ballabhgarh areas harbored higher number of Firmicutes and Proteobacteria and is enriched with microbial xenobiotic degradation pathways. The rural community residing in sea level Ballabhgarh areas has unique microbiome characterized not only by a higher diversity, but also a higher degree of interindividual homogeneity.
Searching for nests of the invasive Asian hornet (Vespa velutina) using radio-telemetry
Authors: Kennedy Peter J. , Ford Scott M. , Poidatz Juliette , Thiéry Denis , Osborne Juliet L.
Published: June 2018

Asian hornets (Vespa velutina) are voracious predators of bees, and are the latest emerging threat to managed and wild pollinator populations in Europe. To prevent establishment or reduce the rate of spread of V. velutina, early detection and destruction of nests is considered the only option. Detection is difficult as their nests are well hidden and flying hornets are difficult to follow over long distances. We address this challenge by tracking individual V. velutina workers flying back to their nests using radio telemetry for the first time, finding five previously undiscovered nests, up to 1.33 km from hornet release points. Hornets can fly with 0.28 g tags if the tag:hornet ratio is less than 0.8. This method offers a step-change in options to tackle the spread of this invader, providing an efficient means of finding V. velutina nests in complex environments to manage this emerging threat to pollinators.
A ratiometric fluorescent hydrogen peroxide chemosensor manipulated by an ICT-activated FRET mechanism and its bioimaging application in living cells and zebrafish
Authors: Xu Kaixin , He Longwei , Yang Xueling , Yang Yunzhen , Lin Weiying
Published: June 2018

A ratiometric fluorescent chemosensor manipulated by an ICT-activated FRET mechanism was engineered for monitoring hydrogen peroxide in living cells and zebrafish.
Light-assisted surface reactions on metal nanoparticles
Authors: Kim Chanyeon , Lee Hyunjoo
Published: June 2018

Light-assisted surface reaction can lower reaction temperature, potentially reducing the energy use by providing light together with heat.
First-principles design of bifunctional oxygen reduction and evolution catalysts through bimetallic centers in metal–organic frameworks
Authors: Zhang Peng , Yang Xuejing , Gao Wang , Hou Xiuli , Mi Jianli , Liu Lei , Huang Jun , Dong Mingdong , Stampfl Catherine
Published: June 2018

Bi-metallic FexCo3−x(THT)2 nanosheets exhibit bifunctional catalytic activity for both the ORR and OER. The ORR occurs on the Co atom, while the active site for the OER is the Fe atom.
Cu2O/TiO2 nanoparticles as visible light photocatalysts concerning C(sp2)–P bond formation
Authors: Hosseini-Sarvari Mona , Jafari Fattaneh , Mohajeri Afshan , Hassani Nasim
Published: June 2018

A novel and efficient method has been developed for the construction of an aromatic-phosphorus (Ar-P) bond under visible light irradiation using Cu2O/TiO2 nanoparticles as inexpensive and available photocatalysts.
Incorporation of Sb5+into CeO2: local structural distortion of the fluorite structure from a pentavalent substituent
Authors: Hiley Craig I. , Fisher Janet M. , Kashtiban Reza J. , Cibin Giannantonio , Thompsett David , Walton Richard I.
Published: June 2018

Sb5+-Substituted CeO2crystallises directly from solution: the substituent cation has octahedral coordination, implying local structural distortion of the fluorite structure.
Selective separation of cadmium(ii) from zinc(ii) by a novel hydrophobic ionic liquid including an N,N,N′,N′-tetrakis(2-methylpyridyl)-1,2-phenylenediamine-4-amido structure: a hard–soft donor combined method
Authors: Wu Hao , Zhang Xiaoxia , Yin Xiangbiao , Inaba Yusuke , Miki Harigai , Takeshita Kenji
Published: June 2018

A novel ionic liquid including an N,N,N′,N′-tetrakis(2-methylpyridyl)-1,2-phenylenediamine-4-amido structure ((IL-1,2-tpbd)+NTf2−) was successfully synthesized.
Triazole vs. triazolium carbene ligands in the site-selective cyclometallation of o-carboranes by M(iii) (M = Ir, Rh) complexes
Authors: Frutos María , Gómez-Gallego Mar , Giner Elena A. , Sierra Miguel A. , Ramírez de Arellano Carmen
Published: June 2018

M(iii)-mediated (M = Ir, Rh) site-selective cage B–H and C–H bond activation in o-carboranylmethyl derivatives has been achieved by switching the electron donating properties of the 1,2,3-triazole ligand.
Emerging investigator series: sunlight photolysis of 2,4-D herbicides in systems simulating leaf surfaces
Authors: Su Lei , Sivey John D. , Dai Ning
Published: June 2018

Herbicides in the 2,4-D family were investigated for their direct photolysis under sunlight in organic solvents and on simulated leaf surfaces.
In situ MnOx/N-doped carbon aerogels from cellulose as monolithic and highly efficient catalysts for the upgrading of bioderived aldehydes
Authors: Zhou Shenghui , Chen Guixian , Feng Xiao , Wang Ming , Song Tao , Liu Detao , Lu Fachuang , Qi Haisong
Published: June 2018

Cellulose-derived monolithic hierarchically porous MnOx/N-doped carbon aerogels exhibited excellent catalytic activity for the upgrading of lignocellulose-derived aldehydes.
Dual-functional cyclic peptide switch on mesoporous nanocontainers for selective CD44 targeting and on–off gatekeeping triggered by conformational transformation
Authors: Lee Jeonghun , Oh Eun-Taex , Choi Min Hyeuk , Kim Ha Gyeong , Park Heon Joo , Kim Chulhee
Published: June 2018

A dual functional cyclic peptide gatekeeper with A6 sequence is designed not only for triggered drug release by conformational transformation of the peptide but also selective targeting of CD44.
Facile fabrication of porous ZnS nanostructures with a controlled amount of S vacancies for enhanced photocatalytic performances
Authors: Lee Jaewon , Ham Sooho , Choi Dayeon , Jang Du-Jeon
Published: June 2018

Barbell-shaped porous and hollow ZnS nanoplates with a controlled amount of S vacancies have been fabricated facilely for enhanced photocatalytic performances.
A two-stage assembly with PEI induced emission enhancement of Au–AgNCs@AMP and the intrinsic mechanism
Authors: Yu Xu , Liu Jiao , Li Hong-Wei , Wu Yuqing
Published: June 2018

The two-stage assembly of Au–AgNCs@AMP and PEI has been carried out with obvious assembly induced emission enhancement (AIEE) properties, which is driven by electrostatic interaction in stage I and micelle formation in stage II, enhancing the quantum yield from 8.64% to 25.02%.
Improved gas sensing properties of silver-functionalized ZnSnO3 hollow nanocubes
Authors: Yin YanYang , Li Feng , Zhang Nan , Ruan Shengping , Zhang Haifeng , Chen Yu
Published: June 2018

Porous silver-functionalized ZnSnO3 hollow nanocubes as a gas sensor with an ultra-fast response and recovery speed for acetone detection.
Highly efficient synthesis of C3-symmetric O-alkyl substituted triphenylenes and related Mannich derivatives
Authors: Berton Giacomo , Borsato Giuseppe , Zangrando Roberta , Gambaro Andrea , Fabris Fabrizio , Scarso Alessandro
Published: June 2018

C3-Symmetric tris-benzyl-O-substituted hexahydroxytriphenylene (HHTP) was prepared through selective ring opening with DIBAL-H in 48% yield (38% from HHTP in a two-step synthesis).
Conductance of ‘bare-bones’ tripodal molecular wires
Authors: Davidson Ross J. , Milan David C. , Al-Owaedi Oday A. , Ismael Ali K. , Nichols Richard J. , Higgins Simon J. , Lambert Colin J. , Yufit Dmitry S. , Beeby Andrew
Published: June 2018

When venturing into the field of tripodal molecular conductors the geometry of the tripod with respect to the surface is a critical factor affecting conductance. Here we examine the behaviour of a tripodal conductor by systematic modifications of a triarylphosphine system.
On the synergy between silver nanoparticles and doxycycline towards the inhibition of Staphylococcus aureus growth
Authors: Silva Heloiza F. O. , de Lima Rayane P. , da Costa Fernanda S. L. , Moraes Edgar P. , Melo Maria C. N. , Sant’Anna Celso , Eugênio Mateus , Gasparotto Luiz H. S.
Published: June 2018

Silver nanoparticles conjugated with doxycycline act synergistically to halt S. aureus growth via inhibition of protein synthesis.
Interconnecting semiconducting molecules with non-conjugated soft linkers: a way to improve film formation quality without sacrifice in charge mobility
Authors: Xiao Wen-Jing , Wang Jiandong , Li Hong-Jiao , Liang Long , Xiang Xuan , Chen Xue-Qiang , Li Jingjing , Lu Zhengquan , Li Wei-Shi
Published: June 2018

For small molecular semiconductors, interconnecting their molecules with non-conjugated soft linkers has been demonstrated to be a good way for improving their film formation quality while keeping their mobility intact for OFETs.
Tribological properties of synthetic base oil containing polyhedral oligomeric silsesquioxane grafted graphene oxide
Authors: Yu Bo , Wang Kai , Hu Yiwen , Nan Feng , Pu Jibin , Zhao Haichao , Ju Pengfei
Published: June 2018

The dispersion of graphene-based materials in lubricating oil is a prerequisite for improving its friction and wear performance.
Synergistic formal ring contraction for the enantioselective synthesis of spiropyrazolones
Authors: Meazza Marta , Kamlar Martin , Jašíková Lucie , Formánek Bedřich , Mazzanti Andrea , Roithová Jana , Veselý Jan , Rios Ramon
Published: June 2018

We report the first ring contraction/formal [6 + 2] cycloaddition using synergistic Pd(0)/secondary amine catalysis, obtaining [5,5]-spiropyrazolone derivatives in excellent yields and stereoselectivities. We detected the key palladium activated intermediate in its protonated form by mass spectrometry and characterized its structure by infrared spectroscopy and DFT calculations, allowing us to propose a conceivable mechanistic pathway for this reaction.
Organic emitter integrating aggregation-induced delayed fluorescence and room-temperature phosphorescence characteristics, and its application in time-resolved luminescence imaging
Authors: Ni Fan , Zhu Zece , Tong Xiao , Xie Mingjuan , Zhao Qiang , Zhong Cheng , Zou Yang , Yang Chuluo
Published: June 2018

A luminophore integrating aggregation-induced delayed fluorescence and room-temperature phosphorescence for time-resolved luminescence imaging.
New enzymatic and mass spectrometric methodology for the selective investigation of gut microbiota-derived metabolites
Authors: Ballet Caroline , Correia Mário S. P. , Conway Louis P. , Locher Theresa L. , Lehmann Laura C. , Garg Neeraj , Vujasinovic Miroslav , Deindl Sebastian , Löhr J.-Matthias , Globisch Daniel
Published: June 2018

New sulfatase-based assay for the selective identification of sulfate esters in human urine and fecal samples.
Catalytic asymmetric synthesis of geminal-dicarboxylates
Authors: Mistry Nisha , Fletcher Stephen P.
Published: June 2018

Here we report a rhodium-catalyzed asymmetric carboxylation of ester-containing allylic bromides to form stereogenic carbon centers bearing two different carboxylates with high yields and enantioselectivities.
Diverse secondary C(sp3)–H bond functionalization via site-selective trifluoroacetoxylation of aliphatic amines
Authors: Tang Yongzhen , Qin Yuman , Meng Dongmei , Li Chaoqun , Wei Junfa , Yang Mingyu
Published: June 2018

A coinage-metal-catalyzed site-selective trifluoroacetoxylation of remote secondary C(sp3)–H bonds for aliphatic amine substrates was developed.
Lipids as integral components in mussel adhesion
Authors: He Yunhong , Sun Chengjun , Jiang Fenghua , Yang Bo , Li Jingxi , Zhong Chao , Zheng Li , Ding Haibing
Published: June 2018

The involvement of lipids in mussel adhesion was demonstrated for the first time in this paper.
Change in collective motion of colloidal particles driven by an optical vortex with driving force and spatial confinement
Authors: Saito Keita , Okubo Shogo , Kimura Yasuyuki
Published: June 2018

Optically driven particles exhibit characteristic collective motions depending on the strength of the driving force and spatial confinement.
Excellent ZT achieved in Cu1.8S thermoelectric alloys through introducing rare-earth trichlorides
Authors: Ge Zhen-Hua , Zhang Yi-Xin , Song Dongsheng , Chong Xiaoyu , Qin Peng , Zheng Fengshan , Feng Jing , Zhao Li-Dong
Published: June 2018

Digenite (Cu1.8S) as a potential p-type thermoelectric (TE) material has attracted extensive attention due to its environmental-friendliness and low toxicity.
Solvent-induced surface hydroxylation of a layered perovskite Sr3FeCoO7−δ for enhanced oxygen evolution catalysis
Authors: Xu Kongliang , Song Fang , Gu Jun , Xu Xiang , Liu Zhenning , Hu Xile
Published: June 2018

Surface hydroxylation significantly improves the catalytic activity of a layered perovskite, Sr3FeCoO7−δ.
Molecular evolution of host materials by regular tuning of n/p ratio for high-performance phosphorescent organic light-emitting diodes
Authors: Liu Di , Wang Fang , Yao Ruijuan
Published: June 2018

By gradually increasing the n/p molar ratio to 2 : 1, the obtained bipolar host material exhibits a turn-on voltage of 2.6 V and an efficiency of 48.1 lm W−1, which is the lowest turn-on voltage and one of the highest power efficiencies ever reported for FIrpic devices containing a single host.
Unidentified quasars among stationary objects from Gaia DR2
Authors: Heintz K. E. , Fynbo J. P. U. , Høg E. , Møller P. , Krogager J.-K. , Geier S. , Jakobsson P. , Christensen L.
Published: June 2018

Here we apply a technique selecting quasar candidates purely as sources with zero proper motions in the Gaia data release 2 (DR2). We demonstrate that this approach is highly efficient toward high Galactic latitudes with ≲25% contamination from stellar sources. Such a selection technique offers very pure sample completeness, since all cosmological point sources are selected regardless of their intrinsic spectral properties within the limiting magnitude of Gaia. We carry out a pilot-study, defining a sample compiled by including all Gaia-DR2 sources within one degree of the north Galactic pole (NGP) selected to have proper motions consistent with zero within 2σ uncertainty. By cross-matching the sample to the optical Sloan Digital Sky Survey (SDSS) and the mid-infrared (MIR) AllWISE photometric catalogues, we investigate the colours of each of our sources. We determine the efficiency of our selection by comparison with previously spectroscopically confirmed quasars. The majority of the zero-proper-motion sources selected here have optical to MIR colours consistent with known quasars. The remaining population may be contaminating stellar sources, but some may also be quasars with colours similar to stars. Spectroscopic follow-up of the zero-proper-motion sources is needed to unveil such a hitherto hidden quasar population. This approach has the potential to allow substantial progress on many important questions concerning quasars, such as determining the fraction of dust-obscured quasars, the fraction of broad absorption line (BAL) quasars, and the metallicity distribution of damped Lyman-α absorbers. The technique could also potentially reveal new types of quasars or even new classes of cosmological point sources.
Purification of Biodiesel Using Activated Carbon Produced from Cocoa Pod Husk
Authors: Rachmat Devita , Agustin Aprillia D. , Risanti Doty D.
Published: June 2018

The purity level of waste cooking oil that use as raw material for biodiesel production has a strong influence on its fuel properties. In this study, activated carbon from cocoa pod husk activated with was used for purification in pre-treatment process of biodiesel production. The result showed that the activated carbon can decrease the water content and FFA and produce well-characterized biodiesel correspond to the Indonesian National Standard requirement.
Longitudinal and Shear Wave Velocities Measurement in Compacted Bentonite for Water Content
Authors: Kimura Shun , Kitayama Kazumi , Takahashi Hideharu , Kimoto Kazushi , Kawamura Katsuyuki , Kikura Hiroshige
Published: June 2018

Bentonite is a good candidate of buffer material for disposal repository of high-level radioactive waste. Understanding groundwater behavior in bentonite buffer material is important in order to evaluate the bentonite buffer performance and guarantee long-term safety. Elastic constants of the bentonite buffer material are important parameters for the long-term safety. Water content in buffer material may have an influence on its elastic properties. For this reason, the monitoring system of the water saturation level in compacted bentonite is required. In this study, the ultrasonic velocity measurement method for evaluation of water content in compacted bentonite was proposed. At first, the effect of a degree of saturation in compacted bentonite on the longitudinal and shear wave velocities was investigated experimentally. In addition, the elastic property, bulk modulus, in unsaturated compacted bentonite were evaluated by ultrasonic velocities. As a result, it can be confirmed that ultrasonic velocities can evaluate a degree of saturation and bulk modulus of compacted bentonite.
ω-3-Fettsäuren und chronische Erkrankungen
Authors: Bayer Wolfgang , Schmidt Karlheinz
Published: June 2018

Fettsäuren werden im menschlichen Organismus nur in begrenztem Umfang synthetisiert, die mehrfach ungesättigten ω-3- und ω-6-Fettsäuren müssen mit der Nahrung aufgenommen werden. Aus Arachidonsäure (AA) entstehen im Stoffwechsel Eicosanoide mit proinflammatorischer Wirkung, aus Eicosapentaensäure (EPA) wenig- bis antiinflammatorische wirkende Eicosanoide. Der AA / EPA-Quotient ist ein Biomarker der Entzündungsbereitschaft. Eine erhöhte Zufuhr von EPA bei gleichzeitiger Einschränkung von AA führt zu antiinflammatorischen Effekten, die sich z. B. bei Morbus Crohn und rheumatoider Arthritis positiv auswirken.
ω-3-Fettsäuren in der Ernährungsmedizin
Authors: Schmiedel Volker
Published: June 2018

Gesundheitlich relevante Effekte von ω-3-Fettsäuren sind fast ausschließlich für die maritimen Fettsäuren Eicospentaensäure und Docosahexaensäure nachgewiesen und nicht für den pflanzlichen Präkursor α-Linolensäure, der nur in geringem Umfang zu EPA und DHA umgewandelt wird. Die beiden Fettsäuren spielen eine bes. Rolle in der Therapie von entzündlichen Erkrankungen und Krankheiten des Nervensystems. Studien belegen positive Wirkungen bei Morbus Crohn, Rheuma, Multipler Sklerose, Migräne und postpartaler Depression.
A Metal-Free Approach for the Synthesis of 2-Tetralones via
Carbanion-Induced Ring Transformation of 2H-Pyran-2-ones
Authors: Singh Fateh , Shetgaonkar Samata
Published: June 2018

A metal-free, ultrasound-assisted approach for the synthesis of highly functionalized 2-tetralones in high yields is described. The process involves ring transformation of 2H-pyran-2-ones with the spirocyclic ketone 1,4-cyclohexandione monoethylene ketal to yield spiro­cyclic ketals and subsequent acid-mediated hydrolysis. This protocol is free from any organometallic reagents, is economical and tolerates a wide range of functional groups.
Monitoring of Heparin Therapy with the Activated Partial Thromboplastin Time and Chromogenic Substrate Assays
Authors: Fey Martin F , Lang Mathis , Furlan Miha , Beck Eugen A
Published: June 2018

Heparin therapy was monitored with the activated partial thromboplastin time (APTT) and with chromogenic substrate assays (factor Xa and factor Ha inhibition) in 100 plasma samples from 47 patients. Heparin concentrations were classified as being below, within or above a defined therapeutic range (TR; 0.2-0.55 units heparin/ml). In a first group of patients (A), all three assays allocated the plasma heparin levels to the same concentration interval with respect to the TR. The most frequent diagnoses in group A were uncomplicated arterial or venous thromboembolism, myocardial infarction with limited tissue necrosis, cardiac surgery without major complications and successfully treated infectious disease. In a second group of patients (B), the results of APTT suggested higher heparin concentrations with respect to the TR than the chromogenic assays. Predominant diagnoses were severe infectious diseases, severe liver disorders, extensive myocardial infarction and postoperative complications after cardiac surgery. The discrepancy between heparin concentrations determined by either APTT or the chromogenic substrate assays is most likely due to a non-heparin related prolongation of APTT caused by the underlying disease.
Concentrated DDAVP: Further Improvement in the Management of Mild Factor VIII Deficiencies
Authors: Ghirardini A , Mariani G , lacopino G , Tirindelli M C , Solinas S , Moretti T
Published: June 2018

This study was carried out to evaluate the pharmacological efficacy of a new concentrated 1 Deamino - (8-D-arginine) - vasopressin (DDAVP) preparation. Concentrated DDAVP (C- DDAVP), (40 μg/mL) was given subcutaneously (s.c.) in hemophilia and von Willebrand Disease (vWD), and the response was evaluated in terms of factor VIII/vWF (VUI/von Willebrand Factor) complex response. This response was also compared to that obtained using the currently available commercial preparation (4 μg/mL) given either s.c. or intravenously (i. v.). The maximal f. VIII response after s.c. C-DDAVP was reached one hour after the injection (x:3.6 times the resting values) with an average decline of 15% at two hours. The response to s.c. C- DDAVP in patients with hemophilia was slightly better than thut obtained with the diluted brand, but the difference did not reach any statistical significance even when the schedules were compared in the same patients. In type I (placed normal subtype) vWD, a higher response in terms of factor VIII :C increase in comparison with hemophiliacs was obtained. Doth Ristocetin cofactor activity (RiCof) and bleeding time responded to this vasopressin analogue, when administered subcutaneously.
Oral Anticoagulant Therapy Control: Evidence that INR Expression Improves the Inter-Laboratory Comparability of Results - The Bologna Oral Anticoagulant Control Exercise
Authors: Palareti G , Coccheri S , Poggi M , Bonetti M , Cervi V , Mazzuca A , Savoia M , Veri L , Fiori F , Gaspari G , Palareti A ,   The Bologna oral anticoagulant control study group
Published: June 2018

The aims of the present study were: l) interlaboratory normalization of prothrombin time (PT) testing for anticoagulant therapy control through calibration of customary thromboplastins against international reference materials, and 2) “on field” validation of the advantages offered by expression of results as International Normalized Ratio (INR) as opposedto percentage activity. PT tests were carried out over 8 days on the same normal subjects (16) and patients on oral an ticoagulants (48) in the 9 laboratories of the Bologna area. The use of customary thromboplastins and coagulometers was maintained in all labs throughout the study. The main results were: 1) the interlaboratory CV of the prothrombin ratios obtained for each sample with all customary thromboplastins (5 different brands) was 15%, but was reduced to levels of 5.8 to 8.9 when using constant thromboplastin brands and batches; 2) the International Sensitivity Index (ISI) values obtained in the different labs were only slightly influenced by the use of different coagulometers; 3) comparable ISI values were obtained through direct calibration with the international reference material and through intermediate calibration with a locally selected standard; 4) use of INR values instead of percentage activity greatly reduced interlaboratory variability and significantly improved uniformity of anticoagulation level measurements. thus reducing the possibility of erroneous prescriptions. The Bologna exercise is therefore of educational value for laboratory and community doctors of the area in understanding and accepting the INR system.
Early Alpha Chain Crosslinking in Human Fibrin Preparations
Authors: Sobel Joan H , Thibodeau Christiane A , Canfield Robert E
Published: June 2018

Purified fibrinogen preparations were clotted under crosslinking conditions and the evolution of α polymers was examined by Western blotting (SDS-PAGE). Monoclonal antibodies that bind to two localized regions within the COOH-terminal portion of the (A)α chains of fibrinogen (F-103, Aα #259-276; F-102, Aα #540-554) were used for immunodetection. Three crosslinked components (100K, 168K, 210K) that each exhibited coincident F-102 and F-103 immunoreactivities were evident as early as γ dimer formation under the in vitro conditions employed. Initial events in the a chain crosslinking process appeared to include interactions between relatively intact chains and a variety of degraded ones that shared the structure Aα #1-276, but differed in the extent to which regions between residues — #276 and — #539 were preserved. Degraded fibrinogen molecules whose Aα chains all terminated before Aα #540-554 were isolated from purified fibrinogen preparations by immunoaffinity chromatography on F-102 Sepharose. Immunoblotting data obtained for the crosslinking capacity of these degraded molecules indicated that early crosslinked components (95 K, 205 K) could form even in the absence of intact a chain partners. This crosslinking, moreover, could progress to the polymer stage. These findings demonstrate that some early crosslinking activity is localized exclusively within regions NH2-terminal to Aα — #540-554 and suggest that fibrinogen molecules with partially degraded Aα chains, which are likely to be circulating under many pathophysiologic conditions, can undergo fibrin stabilization through crosslinking despite a loss of at least 70 COOH-terminal Aα chain residues.
Evidence for an Increased Generation of Prostacyclin in the Microvasculature and an Impairment of the Platelet α-Granule Release in Chronic Renal Failure
Authors: Kyrle Paul A , Stockenhuber Felix , Brenner Brigitte , Gössinger Heinz , Korninger Christian , Pabinger Ingrid , Sunder-Plassmann Gere , Balcke Peter , Lechner Klaus
Published: June 2018

The formation of prostacyclin (PGI2) and thromboxane A2 and the release of beta-thromboglobulin (beta-TG) at the site of platelet-vessel wall interaction, i.e. in blood emerging from a standardized injury of the micro vasculature made to determine bleeding time, was studied in patients with end-stage chronic renal failure undergoing regular haemodialysis and in normal subjects. In the uraemic patients, levels of 6-keto-prostaglandin F1α (6-keto-PGF1α) were 1.3-fold to 6.3-fold higher than the corresponding values in the control subjects indicating an increased PGI2 formation in chronic uraemia. Formation of thromboxane B2 (TxB2) at the site of plug formation in vivo and during whole blood clotting in vitro was similar in the uraemic subjects and in the normals excluding a major defect in platelet prostaglandin metabolism in chronic renal failure. Significantly smaller amounts of beta-TG were found in blood obtained from the site of vascular injury as well as after in vitro blood clotting in patients with chronic renal failure indicating an impairment of the a-granule release in chronic uraemia. We therefore conclude that the haemorrhagic diathesis commonly seen in patients with chronic renal failure is - at least partially - due to an acquired defect of the platelet a-granule release and an increased generation of PGI2 in the micro vasculature.
Inhibition in Purified Systems and in Human Plasma of Chimaeric Plasminogen Activators Consisting of the NH2-Terminal Region of Tissue-Type Plasminogen Activator and the COOH-Terminal Region of UrokinaseType Plasminogen Activator
Authors: Lijnen H R , Nelles L , Van Hoef B , De Cock F , Collen D
Published: June 2018

Recombinant chimaeric molecules between tissue-type plasminogen activator (t-PA) and single chain urokinase-type plasminogen activator (scu-PA) or two chain urokinase-type plasminogen activator (tcu-PA) have intact enzymatic properties of scu-PA or tcu-PA towards natural and synthetic substrates (Nelles et al., J Biol Chem 1987; 262: 10855-10862). In the present study, we have compared the reactivity with inhibitors of both the single chain and two chain variants of recombinant u-PA and two recombinant chimaeric molecules between t-PA and scu-PA (t-PA/u-PA-s: amino acids 1-263 of t-PA and 144-411 of u-PA; t-PA/u-PA-e: amino acids 1-274 of t-PA and 138-411 of u-PA). Incubation with human plasma in the absence of a fibrin clot for 3 h at 37° C at equipotent concentrations (50% clot lysis in 2 h), resulted in significant fibrinogen breakdown (to about 40% of the normal value) for all two chain molecules, but not for their single chain counterparts. Preincubation of the plasminogen activators with plasma for 3 h at 37° C, resulted in complete inhibition of the fibrinolytic potency of the two chain molecules but did not alter the potency of the single chain molecules. Inhibition of the two chain molecules occurred with a t½ of approximately 45 min. The two chain variants were inhibited by the synthetic urokinase inhibitor Glu-Gly-Arg-CH2CCl with apparent second-order rate constants of 8,000-10,000 M−1s−1, by purified α2-antiplasmin with second-order rate constants of about 300 M−1s−1, and by plasminogen activator inhibitor-1 (PAI-1) with second-order rate constants of approximately 2 × 107 M−1s−1.

It is concluded that the reactivity of single chain and two chain forms of t-PA/u-PA chimaers with inhibitors is very similar to that of the single and two chain forms of intact u-PA.
Antithrombotic Properties of Heparin in a Neonatal Piglet Model of Thrombin-Induced Thrombosis
Authors: Schmidt B , Buchanan M R , Ofosu F , Brooker L , Hirsh J , Andrew M
Published: June 2018

The relative deficiency of antithrombin III (AT III) in neonatal plasma results in lower recovery of heparin in some assay systems. It is uncertain whether low AT III levels also limit the antithrombotic effects of heparin in this age group. We therefore compared the antithrombotic properties of heparin in mature pigs and newborn piglets, whose coagulation and inhibitor system closely resembles that of the human neonate. Animals were pretreated with saline, 10 or 25 U/kg heparin (n ≥16 per age group and dose). Following an injection of 100 U/kg thrombin, systemic 125I-fibrinogen consumption and local 125I-fibrinogen incorporation into jugular venous stasis thrombi were measured. Significantly more 125I-fibrinogen was consumed in piglets than in pigs systemically (p <0.0001), as well as within the occluded vein segment (p = 0.0112), largely because heparin was less effective in piglets than in pigs. This neonatal resistance to heparin could not be explained by lower heparin levels in the newborn animals. However, pretreatment with AT III concentrate significantly improved the antithrombotic properties of heparin in this age group (p <0.0001). We conclude that physiologically low AT III levels reduce the efficacy of heparin in neutralizing thrombin activity in newborn piglets. We speculate that AT III deficiency may also limit the antithrombotic properties of heparin in newborn infants with thrombotic disease.
Isolation of Fibrinogen Aα-Chain by Affinity Chromatography on Concanavalin A-Sepharose
Authors: Bögli Christa , Hofer Anita , Furlan Miha
Published: June 2018

A method was developed for isolation of the Aa-chain from S-carboxamidomethylated fibrinogen. A mixture of the three constituent polypeptide chains of human fibrinogen was applied onto a column of concanavalin A-Sepharose. While the carbohydrate-free Aα-chain was not delayed on the affinity chromatography column, both glycosylated subunit chains, Bβ- and γ-chain, were adsorbed to the insolubilized lectin and were quantitatively eluted from the column with 0.2 M methyl-α-D-mannoside. SDS- electrophoresis on polyacrylamide gel was employed for analysis of chromatographic fractions. Complete recovery of the Aα-chain was observed. The described procedure is very simple and permits isolation of large amounts of pure Aα-chain from S-carboxamidomethylated fibrinogen.
Autoradiographic Observation of Platelets in Cerebrovascular Injuries Induced by Arachidonic Acid and its Prevention by Ticlopidine
Authors: Fujimoto Tsukasa , Suzuki Hidenori , Tanoue Kenjiro , Fukushima Yoshiharu , Yamazaki Hiroh
Published: June 2018

The behavior of circulating 111In-labeled platelets in cerebrovascular injuries induced by arachidonic acid injection was studied. Fourteen rabbits were pretreated with the antiplatelet agent ticlopidine, and 10 rabbits were used for controls. Arachidonic acid (AA, 0.7 mg/kg) was injected into the internal carotid artery. Prior to the injection, platelets labeled with 111In- oxine were injected for autoradiography of the brain. Evans blue was injected as an indicator of blood-brain barrier disturbance. Nine control animals showed marked blue staining, and one showed slight blue staining. Seven out of the 14 pretreated animals showed slight or no staining, while 7 showed intensive staining. The distributions of the blue staining and the radioactivity showed high correlation. In the rabbits whose platelet aggrega- bility was depressed by ticlopidine, lower blue staining as well as lower radioactivity was observed. Our findings suggest that activated platelets have an important role in the genesis of cerebrovascular injuries.
Detection and Quantitative Evaluation of Lupus Circulating Anticoagulant Activity
Authors: Rosner Esther , Pauzner Rachel , Lusky Ayala , Modan Michaela , Many Amira
Published: June 2018

Sixty-six SLE patients were studied for the presence of lupus type circulating anticoagulant. Forty-nine percent of them showed activity of this anticoagulant. The sensitivity of various coagulation tests was compared. Recalcification time was found to be the most sensitive screening test and the kaolin clotting time mixture test, the best for determining the presence of the anticoagulant.

Tissue thromboplastin inhibition test detected only half of the patients in whom the anticoagulant was found by recalcification time and kaolin clotting time mixture test.

APTT, using 2 different reagents, resulted in 73% and 52% false negatives. A numerical index for determining the presence of the anticoagulant and its quantitative evaluation is suggested.

The association between thromboembolic events, recurrent abortions and the different coagulation tests is shown.
Effect of a Synthetic Thrombin Inhibitor MCI-9038 on Experimental Models of Disseminated Intravascular Coagulation in Rabbits
Authors: Hara H , Tamao Y , Kikumoto R , Okamoto S
Published: June 2018

We examined the effect of a synthetic thrombin inhibitor, MCI-9038, on two experimental animal models of disseminated intravascular coagulation (DIC).

In a model that DIC induced by the intravenous infusion of thrombin, MCI-9038 suppressed the decrease of platelet count by about 50% at a dose of 0.2 μg/kg/min and almost completely at 2 μg/kg/min. When MCI-9038 was administered orally, the suppressive effect was also observed. Heparin suppressed the platelet count decrease by about 50% at 1 unit/kg/min.

In another model of DIC induced by lactic acid and tissue thromboplastin infusion, MCI-9038 prevented the decrease of platelet count and the consumption of coagulation factors. The suppression effect by about 50% on these changes was observed at a dose of 3.16 μg/kg/min. Thromboelastogram pattern indicating the consumption coagulopathy in control experiments was normalized by the MCI-9038 administration. Heparin suppressed the decrease of fibrinogen content as effectively as MCI-9038, but it was less effective on the platelet count decrease.

From these results, it was concluded that MCI-9038 might be useful for the treatment of DIC.
Hereditary Heparin Cofactor II Deficiency and the Risk of Development of Thrombosis
Authors: Bertina R M , van der Linden I K , Engesser L , Muller H P , Brommer E J P
Published: June 2018

Heparin cofactor II (HC II) levels were measured by electroimmunoassay in healthy volunteers, and patients with liver disease, DIC, proteinuria or a history of venous thrombosis. Analysis of the data in 107 healthy volunteers revealed that plasma HC II increases with age (at least between 20 and 50 years). HC II was found to be decreased in most patients with liver disease (mean value: 43%) and only in some patients with DIC. Elevated levels were found in patients with proteinuria (mean value 145%). In 277 patients with a history of unexplained venous thrombosis three patients were identified with a HC II below the lower limit of the normal range (60%). Family studies demonstrated hereditary HC II deficiency in two cases. Among the 9 heterozygotes for HC II deficiency only one patient had a well documented history of unexplained thrombosis. Therefore the question was raised whether heterozygotes for HC II deficiency can also be found among healthy volunteers. When defining a group of individuals suspected of HC II deficiency as those who have a 90% probability that their plasma HC II is below the 95% tolerance limits of the normal distribution in the relevant age group, 2 suspected HC II deficiencies were identified among the healthy volunteers. In one case the hereditary nature of the defect could be established.

It is concluded that hereditary HC II deficiency is as prevalent among healthy volunteers as in patients with thrombotic disease. Further it is unlikely that heterozygosity for HC II deficiency in itself is a risk factor for the development of venous thrombosis.
A Sensitive Solid-Phase Immunosorbent Assay for Tissue-Type Plasminogen Activator Activity in Plasma Using Trinitrobenzoylated Poly-D-Lysine as a Stimulator for Plasminogen Activation
Authors: Petersen Lars Christian , Handest Peter , Brender Jytte , Selmer Johan , Jørgensen Maja , Thorsen Sixtus
Published: June 2018

A sensitive, specific and precise immunosorbent assay for tissue-type plasminogen activator (t-PA) activity in plasma was developed. It measured the single-chain and the two-chain forms of t-PA with equal sensitivity. The assay involved (I) coating of wells in microtiter plates with a monoclonal antibody directed towards an epitope on t-PA apart from the catalytic active site, (II) binding of t-PA to the solid-phase antibody, (III) activation of plasminogen by antibody-bound t-PA in the presence of a new potent stimulator, trinitrobenzyl alkylated poly-D-lysine (TNB-poly-D-Lysine) and measurement of plasmin activity with D-Val-Leu-Lys-pNA. Plasma samples were acid-treated and diluted 80 times in order to minimize the inhibitory effect of plasma on the assays. The assay could be performed within one working day with precoated microtiter plates.

The sensitivity of the assay for t-PA in plasma was 1 pM (~70 ng/1). The recoveries of single-chain and two-chain t-PA added to plasma was 97-104%. The intraassay coefficient of variation was 3.4-5.1% and the interassay coefficient of variation was 7.8-18%. Resting values of t-PA in plasma for 42 healthy subjects ranged between 0 and 30 pM (median: 4.1 pM). The values after 10 min venous occlusion ranged between 1.2 and 520 pM (median: 100 pM). The t-PA concentrations determined by the immunosorbent assay correlated well with euglobulin clot lysis time measurements (r = 0.940).
The Use of Labelled Fibrinogen in the Diagnosis of Venous Thrombosis
Authors: van der Maas A. P. C , Teulings F. A. G , den Ottolander G. J. H
Published: June 2018

In 16 normal test persons and 18 patients with venous thrombosis a comparing study with 131I-fibrinogen was made between scintillation counting and measuring the t1/2 in the circulating blood.

With both techniques the difference in regard to normals was significant.

Measuring the t1/2, however, is more sensitive and is to be prefered.
Enhanced Blood Coagulation and Fibrinolysis in a Patient with Primary Amyloidosis
Authors: Perlin E , Brakman P , Berg H. S , Kirchner P. T , Moquin R. B , Astrup T
Published: June 2018

A case of primary amyloidosis associated with blood coagulation abnormalities is presented. Enhancement of coagulation, suspected because of acceleration of the thromboplastin activation test and of abnormal thrombelastography patterns, was confirmed by the presence of thrombi observed at necropsy. Increased systemic fibrinolysis was evidenced by accelerated clot lysis, increased euglobulin activity, and decreased plasminogen. The presence of fragmented red cells in the peripheral blood smear was consistent with a microangiopathic process. Despite these abnormalities, there were no major changes in levels of coagulation factors. Episodes of massive bleeding occurred when major changes in coagulation or fibrinolysis were absent, supporting the suggestion that vascular infiltration by amyloid is a major cause of hemorrhage.
Experimentelle Immunhämolyse und Blutgerinnung
Authors: Janzarik Hilde , Köppler E , Lasch H. G
Published: June 2018

Serum von Enten, die gegen gewaschene Kaninchen-Erythrozyten immunisiert worden waren, wurde Kaninchen injiziert und dadurch eine Hämolyse ausgelöst. Als Kontrolle dienten Kaninchen, die normales Entenserum erhielten. Bei den meisten Hämolysetieren trat ein Schockzustand auf. Es wurden Fibrinogen, Thrombozytenzahl, die Faktoren II, V und VII sowie R-Zeit, K-Zeit und maximale Festigkeit im Thrombelastogramm bestimmt und ein Abfall der einzelnen Faktoren beobachtet, der als Verbrauchskoagulopathie auf gef aßt werden muß. Das Thrombelastogramm läßt eine Kompensation dieser Vorgänge innerhalb der Globalgerinnung erkennen. Bei den Kontrollieren trat kein Schock auf, der Fibrinogenspiegel, die Aktivität der Faktoren II und VII und die maximale Amplitude zeigten keine oder nur unwesentliche Veränderungen. Dagegen fiel die Thrombozytenzahl und die Faktor-V-Aktivität in demselben Maße ab wie bei den Hämolysetieren.