bluuebunny/crossref_metadata_2025 huggingface dataset:
Near‐Real‐Time Estimates on Earthquake Rupture Directivity Using Near‐Field Ground Motion Data From a Dense Low‐Cost Seismic Network
Authors: Jan Jyh Cherng , Huang Hsin‐Hua , Wu Yih‐Min , Chen Chien‐Chih , Lin Cheng‐Horng
Published: July 2018

Rupture directivity of earthquakes could amplify ground shaking and cause serious earthquake hazards. Its timely information is therefore of great importance for early shaking alerts and emergency responses. To this end, we test the feasibility of using near‐field (<25 km) ground motion data from a dense low‐cost seismic network in Taiwan to constrain directivity information and provide warning for far‐field areas. The method is simple and robust, based on the real‐time shaking map interpolation and directional attenuation regression analysis. Applications to 16 moderate‐ to large‐magnitude earthquakes in Taiwan and California show that the directivity can be stably obtained within 17 s and agrees well with previous studies when available. An indicator of the strength of directivity amplification is also defined and reveals a prevalence of strong directivity effect for ML ≥ 6.0 earthquakes in Taiwan. Such near‐real‐time directivity information can therefore be useful in earthquake early warning systems for providing more accurate ground shaking alerts.
Gravity‐Independent Grain Size Segregation in Experimental Granular Shear Flows as a Mechanism of Layer Formation
Authors: Siman‐Tov Shalev , Brodsky Emily E.
Published: July 2018

Fine grain bands in faults are normally interpreted as indicative of slip localization. However, grains can migrate systematically during shear resulting in nonintuitive effects on the final structure. Here we report the results of shear experiments performed on natural granular materials and discuss their possible implications for natural shear systems. We sheared dry grains in a rheometer over a range of velocities, followed the structural evolution with video during shear, and characterized the final structures. Fine particles comminuted during high‐velocity shear migrated from the highest shear rate regions to a layer where shear rate is near zero. This migration is an example of shear segregation that is driven by grain‐inertia effects. The segregation forms an apparent shear band displaced from the principal slip surface and has a stabilizing effect on subsequent flow. This shear segregation may result in fine‐particle layers and slip localization in natural shear zones.
Maternal betaine supplementation affects fetal growth and lipid metabolism of high-fat fed mice in a temporal-specific manner
Authors: Joselit Yaelle , Nanobashvili Khatia , Jack-Roberts Chauntelle , Greenwald Esther , Malysheva Olga V , Caudill Marie A , Saxena Anjana , Jiang Xinyin
Published: July 2018

Background/objectives

Maternal obesity increases the risk of gestational diabetes mellitus (GDM), which results in fetal overgrowth and long-lasting metabolic dysfunctioning in the offspring. Previous studies show that maternal choline supplementation normalizes fetal growth and adiposity of progeny from obese mice. This study examines whether supplementation of betaine, a choline derivative, has positive effects on fetal metabolic outcomes in mouse progeny exposed to maternal obesity and GDM.

Methods

C57BL/6J mice were fed either a high-fat (HF) diet or a control (normal-fat, NF) diet and received either 1% betaine (BS) or control untreated (BC) drinking water 4–6 weeks before timed-mating and throughout gestation. Maternal, placental, and fetal samples were collected for metabolite and gene-expression assays.

Results

At E12.5, BS prevented fetal and placental overgrowth and downregulated glucose and fatty acid transporters (Glut1andFatp1) and the growth-promoting insulin-like growth factor 2 (Igf2) and its receptorIgf1rin the placenta of HF, glucose-intolerant dams (P < 0.05). However, these effects disappeared at E17.5. At E17.5, BS reduced fetal adiposity and prevented liver triglyceride overaccumulation in HF versus NF fetuses (P < 0.05). BS fetal livers had enhanced mRNA expression of microsomal triglyceride transfer protein (Mttp) (P < 0.01), which promotes VLDL synthesis and secretion. Although we previously reported that maternal choline supplementation downregulated mRNA expression of genes involved in de novo lipogenesis in fetal livers, such alterations were not observed with BS, suggesting differential effects of betaine and choline on fetal gene expression.

Conclusion

We propose a temporal-specific mechanism by which maternal BS influences fetal growth and lipid metabolic outcomes of HF mice during prenatal development.
Evaluation of thermodynamic equations of state across chemistry and structure in the materials project
Authors: Latimer Katherine , Dwaraknath Shyam , Mathew Kiran , Winston Donald , Persson Kristin A.
Published: July 2018

Thermodynamic equations of state (EOS) for crystalline solids describe material behaviors under changes in pressure, volume, entropy and temperature, making them fundamental to scientific research in a wide range of fields including geophysics, energy storage and development of novel materials. Despite over a century of theoretical development and experimental testing of energy–volume (E–V) EOS for solids, there is still a lack of consensus with regard to which equation is indeed optimal, as well as to what metric is most appropriate for making this judgment. In this study, several metrics were used to evaluate quality of fit for 8 different EOS across 87 elements and over 100 compounds which appear in the literature. Our findings do not indicate a clear “best” EOS, but we identify three which consistently perform well relative to the rest of the set. Furthermore, we find that for the aggregate data set, the RMSrD is not strongly correlated with the nature of the compound, e.g., whether it is a metal, insulator, or semiconductor, nor the bulk modulus for any of the EOS, indicating that a single equation can be used across a broad range of classes of materials.
Toll-Like Receptor 4 (TLR4) Expression Affects Schwann Cell Behavior in vitro
Authors: Zhang Huanhuan , Shao Zhiwei , Zhu Yun , Shi Lingyu , Li Zhihao , Hou Rui , Zhang Chunwang , Yao Dengbing
Published: July 2018

Peripheral nerve injury can result in the decreased quality of life and bring us economic burden on society and individuals. Wallerian degeneration (WD) is critical for nerve degeneration and regeneration, but the mechanisms of WD are still elusive. Here, we report the effect of Toll-like receptor 4 (TLR4) on cultured Schwann cells (SCs) in vitro. The data showed that TLR4 expression was up-regulated after sciatic nerve injury of rat. TLR4 was expressed in cultured SCs. Enhanced or silenced expression of TLR4 affected SC proliferation, migration, apoptosis and relative gene expression. Furthermore, altered expression of TLR4 resulted in expression changes in c-Jun, ERK and catenin but not AKT and c-Fos pathways in SCs. These results suggested that TLR4 may be an important effective target in peripheral nerve degeneration and/or regeneration during WD in future investigations.
Frequency and pattern of exercise and depression after two years in older Japanese adults: the JAGES longitudinal study
Authors: Kanamori Satoru , Takamiya Tomoko , Inoue Shigeru , Kai Yuko , Tsuji Taishi , Kondo Katsunori
Published: July 2018

Few have clarified what exercise frequencies and patterns (e.g. alone or with others) are effective for preventing depression in older adults. We examined the relationship between total frequency and/or pattern of exercise and the risk of depression after two years in older Japanese adults. We used a sub-sample of the Japan Gerontological Evaluation Study (JAGES) performed in 2011 and 2013. The sample for analysis was 1,422 adults aged 65 years or older without depression and low physical strength in 2011. All variables were assessed with a questionnaire including the geriatric depression screening scale (GDS-15). Binomial logistic regression analysis was used to examine the relationships between exercise in 2011 and depression in 2013 (0 = non-depression, 1 = depression). The adjusted odds ratio (OR) for later depression was 0.52 (95% confidence intervals: 0.33–0.81) for exercise two or more times a week compared to non-exercisers. The OR for exercisers who exercise with others even a little (Ewo) was 0.53 (0.34–0.84) compared to non-exercisers. Among combinations of frequency and pattern, the OR for Ewo who exercise two or more times a week was 0.40 (0.24–0.68) compared to non-exercisers. Exercising at least twice a week and/or with others may be useful in preventing depression in older adults.
Sentinel nurseries to assess the phytosanitary risks from insect pests on importations of live plants
Authors: Kenis Marc , Li Hongmei , Fan Jian-ting , Courtial Beatrice , Auger-Rozenberg Marie-Anne , Yart Annie , Eschen René , Roques Alain
Published: July 2018

Ornamental plants represent a major pathway of invasion for alien pests worldwide. Commodity risk analyses are carried out to assess the risk posed by a new trade in a commodity, but they are restricted by our limited knowledge of the pests carried by traded plants. We used the sentinel nursery technique to identify insects attacking woody plants imported into Europe. We established two sentinel nurseries in China, with five traded Asian plants. These nurseries were monitored for two years to obtain lists of insects that can be expected on these commodities. These records were compared with those obtained from literature surveys, which are usually the sources of information available to pest risk assessors. At each site, 105 insect species and host associations were found on sentinel plants and 90% of these associations had not been found in a previous literature survey of insect pests of the five plants. Nearly 80% of these associations were not found in ana posterioriliterature survey. An assessment classified 9%, 7% and 84% of the insect records as presenting a high, moderate and low likelihood of introduction, respectively. These results show the benefit of sentinel nurseries to identify potential infestation of plant commodity imports.
Novel 3D Structure Based Model for Activity Prediction and Design of Antimicrobial Peptides
Authors: Liu Shicai , Bao Jingxiao , Lao Xingzhen , Zheng Heng
Published: July 2018

The emergence and worldwide spread of multi-drug resistant bacteria makes an urgent challenge for the development of novel antibacterial agents. A perspective weapon to fight against severe infections caused by drug-resistant microorganisms is antimicrobial peptides (AMPs). AMPs are a diverse class of naturally occurring molecules that are produced as a first line of defense by all multi-cellular organisms. Limited by the number of experimental determinate 3D structure, most of the prediction or classification methods of AMPs were based on 2D descriptors, including sequence, amino acid composition, peptide net charge, hydrophobicity, amphiphilic, etc. Due to the rapid development of structural simulation methods, predicted models of proteins (or peptides) have been successfully applied in structure based drug design, for example as targets of virtual ligand screening. Here, we establish the activity prediction model based on the predicted 3D structure of AMPs molecule. To our knowledge, it is the first report of prediction method based on 3D descriptors of AMPs. Novel AMPs were designed by using the model, and their antibacterial effect was measured by in vitro experiments.
Surface plasmon resonance based sensor for the detection of glycopeptide antibiotics in milk using rationally designed nanoMIPs
Authors: Altintas Zeynep
Published: July 2018

Glycopeptide antibiotics are known as the last resort for the treatment of serious infections caused by Gram-positive bacteria. The use of milk products contaminated with these antibiotic residues leads to allergic reactions and sensitivity in human. Also, long-term consumption of milk products containing low levels of these antibiotics may cause the relevant bacteria to build up resistance to these last resort antibiotics. Sensitive, rapid and effective quantification and monitoring systems play a key role for their determination in milk products. Hence, molecularly imprinted nanostructures were rationally designed in this work to produce high affinity synthetic receptors to be coupled with a surface plasmon resonance sensor for the analysis of glycopeptide antibiotics in milk samples. The nanoMIP-SPR sensor enabled vancomycin quantification with the LODs of 4.1 ng mL−1 and 17.7 ng mL−1 using direct and competitive assays, respectively. The recoveries rates for two sensor methods ranged in 85–110% with RSDs below 7%. The affinity between the nanoMIP receptors and the target molecule (dissociation constant: 1.8 × 10−9 M) is mostly superior to natural receptors and other synthetic receptors. Unlike other methods commonly employed for the detection of milk contaminants this approach is extremely simple, fast and robust, and do not require pre-sample treatment.
Effects of Threat Conditioning on the Negative Valanced Systems and Cognitive Systems
Authors: Fernández Rodrigo S. , Picco Soledad , Messore Fernando , Pedreira María E.
Published: July 2018

Threat conditioning is held as a model of anxiety disorders. However, this approach is focused on implicit responses evaluated in a single day. Here, we evaluated negative-valence, positive-valence and cognitive-systems in order to evaluate the extent to which threat conditioning models anxiety disorders. Subjects underwent threat conditioning and five-minutes (Short-term evaluation) or 48 hs (Long-term evaluation) later, both groups performed several tasks targeting cognitive-systems and valenced-systems. In the short-term evaluation, successful conditioning maintained state-anxiety and increased the aversiveness representation of the CS+ and the valuation for negative events. Reaction-times for the CS+ were faster, reflecting an attentional bias toward threat. In the long-term evaluation, participants represented the CS+ as more aversive and generalized to all stimuli. Reaction-times showed a more restricted attentional bias. Threat conditioning alters the negative-valence systems and creates a cognitive bias, which is transformed by memory consolidation, suggesting that this protocol could be a useful resource to understand the deficits associated with anxiety disorders.
Diversity among endothelial cell lines revealed by Raman and Fourier-transform infrared spectroscopic imaging
Authors: Szafraniec Ewelina , Wiercigroch Ewelina , Czamara Krzysztof , Majzner Katarzyna , Staniszewska-Slezak Emilia , Marzec Katarzyna M. , Malek Kamilla , Kaczor Agnieszka , Baranska Malgorzata
Published: July 2018

A methodology of examination and characterization of popular human endothelial cells lines.
Luminescent switch sensors for the detection of biomolecules based on metal–organic frameworks
Authors: Zhang Qi , Wang Chen-Feng , Lv Yun-Kai
Published: July 2018

The applications of MOFs-based luminescent sensors for biomolecules sensing via a “turn on” or “turn off” response have been reviewed.
Targetable, two-photon fluorescent probes for local nitric oxide capture in the plasma membranes of live cells and brain tissues
Authors: Zhang Xinfu , Wang Benlei , Xiao Yi , Wang Chao , He Ling
Published: July 2018

A plasma membrane-targetable two-photon fluorescent probe for capturing nitric oxide in cells and brain tissues.
Multi-pesticide residue analysis by high resolution mass spectrometry in complementary matrices: wheat flour, lettuce and apple samples
Authors: Chiarello Marilda , Moura Sidnei
Published: July 2018

Nowadays, food contamination with pesticide residues is prevalent, which can cause problems to human health.
Fluorescent chemodosimeter for quantification of cystathionine-γ-synthase activity in plant extracts and imaging of endogenous biothiols
Authors: Agarwalla Hridesh , Anila H. A. , Ali Firoj , Pradhan Swaraj Rashmi , Ganguly Bishwajit , Pramanik Sumit Kumar , Das Amitava
Published: July 2018

Chemodosimetric reagent for quantification of cystathionine-γ-synthase and mapping endogenous biothiols with luminescence ON response.
A novel exonuclease-assisted isothermal nucleic acid amplification with ultrahigh specificity mediated by full-length Bst DNA polymerase
Authors: Ye Xin , Li Yang , Wang Lijuan , Fang Xueen , Kong Jilie
Published: July 2018

A novel exonuclease-assisted isothermal amplification to amplify and determine nucleic acids very sensitively and with ultrahigh specificity.
Experimental and computational studies on H2O-promoted, Rh-catalyzed transient-ligand-free ortho-C(sp2)–H amidation of benzaldehydes with dioxazolones
Authors: Ding Jun , Jiang Wei , Bai He-Yuan , Ding Tong-Mei , Gao Dafang , Bao Xiaoguang , Zhang Shu-Yu
Published: July 2018

We develop an efficient and convenient ligand-free, rhodium-catalyzed ortho-C(sp2)–H amidation of benzaldehydes with dioxazolones using H2O as the key promoter.
A photocaged fluorescent probe for imaging hypochlorous acid in lysosomes
Authors: Ren Mingguang , Li Zihong , Nie Jing , Wang Li , Lin Weiying
Published: July 2018

By combining the advantages of the photocaging technology and traditional analyte-responsive fluorescent probes, we designed and synthesized the first photocaged lysosomal-targeted fluorescent HOCl probe (PL-HA), which is capable of remote light-controlled intracellular target recognition of HOCl in lysosomes.
A highly GSH-sensitive SN-38 prodrug with an “OFF-to-ON” fluorescence switch as a bifunctional anticancer agent
Authors: Whang Chang-Hee , Yoo Eunsoo , Hur Seong Kwon , Kim Kyeong Soo , Kim Dongin , Jo Seongbong
Published: July 2018

A DNS-SN38 prodrug that is capable of GSH-sensitive activation of quenched fluorescence for bifunctional application.
Theoretical investigation on the interaction between RhIII octaethylporphyrin and a graphite basal surface: a comparison study of DFT, DFT-D, and AFM
Authors: Tada Kohei , Maeda Yasushi , Ozaki Hiroyuki , Tanaka Shingo , Yamazaki Shin-ichi
Published: July 2018

Using density functional theory based calculations and atomic-force-microscopy observations, we investigated the interaction between [RhIII(OEP)(Cl)] (OEP = octaethylporphyrin) and a graphite basal surface, and the electronic structure of [RhIII(OEP)(Cl)]/graphite.
Observation of an electric field-induced interface redox reaction and magnetic modification in GdOx/Co thin film by means of depth-resolved X-ray absorption spectroscopy
Authors: Sakamaki Masako , Amemiya Kenta
Published: July 2018

We study an electric field-induced redox reaction at the interface of GdOx/Co thin film, by means of soft X-ray absorption spectroscopy.
Emerging photonic architectures in two-dimensional opto-electronics
Authors: Brar Victor W. , Sherrott Michelle C. , Jariwala Deep
Published: July 2018

This review summarizes recent developments in opto-electronic device architectures comprising van der Waals two-dimensional materials for enhanced light–matter interactions.
Effect of the cation sublattice composition of tin-based type-I clathrates on their low-temperature thermal properties
Authors: Novikov V. V. , Pilipenko K. S. , Matovnikov A. V. , Mitroshenkov N. V. , Likhanov M. S. , Tyablikov A. S. , Shevelkov A. V.
Published: July 2018

We performed an experimental study on thermal properties of the Sn18In6As21.5I8 clathrate by measuring temperature dependencies of its heat capacity (2–300 K) and thermal expansion (5–300 K).
Phenylacetylene polymerisation mediated by cationic cyclometallated palladium(ii) complexes bearing benzylidene 2,6-diisopropylphenylamine and its derivatives as ligands
Authors: Joseph M. Cassiem. , Swarts Andrew J. , Mapolie Selwyn F.
Published: July 2018

Novel cationic palladacycle complexes of benzylidene-2,6-diisopropylphenylamine were found to be efficient catalyst precursors in the polymerization of phenylacetylene.
Adverse effects of interlayer-gliding in layered transition-metal oxides on electrochemical sodium-ion storage
Authors: Sun Yang , Guo Shaohua , Zhou Haoshen
Published: July 2018

The gliding of transition-metal slabs in layered Na containing oxides would limit the battery performance in several crucial aspects.
Life cycle assessment of adipic acid production from lignin
Authors: Corona Andrea , Biddy Mary J. , Vardon Derek R. , Birkved Morten , Hauschild Michael Z. , Beckham Gregg T.
Published: July 2018

In this study, we performed a life cycle assessment (LCA) on an emerging lignin upgrading process, namely the production of biobased adipic acid.
Oxidant-free oxidation of C–H bonds by cathodic hydrogen evolution: a phosphonic Kolbe oxidation/cyclization process
Authors: Zhang Lei , Zhang Zhenxing , Zhang Jianning , Li Kangle , Mo Fanyang
Published: July 2018

An anodic oxidation/cyclization of 2-(aryl)aryl phosphonic acid monoesters for ethoxy dibenzooxaphosphorin oxide synthesis has been developed.
ICP-MS for the analysis at the nanoscale – a tutorial review
Authors: Meermann Björn , Nischwitz Volker
Published: July 2018

The scope of this tutorial review is (i) to provide an overview on ICP-MS based techniques for the analysis of ENPs and natural nanoparticles/colloids by (a) “stand alone” ICP-MS and (b) hyphenated techniques; (ii) highlighting the benefits and pitfalls of each technique as well as providing practical advice regarding method development; (iii) illustrating the possibilities and limitations of each technique by practical applications from the recent literature.
Polysaccharides fromBurkholderiaspecies as targets for vaccine development, immunomodulation and chemical synthesis
Authors: Cloutier Maude , Muru Kevin , Ravicoularamin Gokulakrishnan , Gauthier Charles
Published: July 2018

This review focuses on the structural elucidation and biological activities of polysaccharides produced byBurkholderiaspecies and on the synthesis of their oligosaccharide mimics.
Three-dimensional graphene-based polymer nanocomposites: preparation, properties and applications
Authors: Guan Li-Zhi , Zhao Li , Wan Yan-Jun , Tang Long-Cheng
Published: July 2018

A schematic illustration of the fabrication strategies and applications of 3D-GPNCs is shown.
Highly crumpled nanocarbons as efficient metal-free electrocatalysts for zinc–air batteries
Authors: Xiao Yukun , Cheng Zhihua , Zhao Yang , Qu Liangti
Published: July 2018

A highly nanocrumpled and nitrogen, phosphorus-codoped nanocarbon for efficient zinc–air batteries is fabricated through a one-step and facile pyrolysis strategy.
MoS2-modified porous gas diffusion layer with air–solid–liquid interface for efficient electrocatalytic water splitting
Authors: Sui Chenxi , Chen Kai , Zhao Liming , Zhou Li , Wang Qu-Quan
Published: July 2018

The formation and adsorption of bubbles on electrodes weaken the efficiency of gas evolution reactions such as the hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) by hindering proton transfer and consuming nucleation energy.
A simple, label-free, electrochemical DNA parity generator/checker for error detection during data transmission based on “aptamer-nanoclaw”-modulated protein steric hindrance
Authors: Fan Daoqing , Fan Yongchao , Wang Erkang , Dong Shaojun
Published: July 2018

The first electrochemical DNA parity generator/checker system for error detection during data transmission was constructed based on “aptamer-nanoclaw”-modulated protein steric hindrance.
Mitochondrial abnormalities in Parkinson's disease and Alzheimer's disease: can mitochondria be targeted therapeutically?
Authors: Macdonald Ruby , Barnes Katy , Hastings Christopher , Mortiboys Heather
Published: July 2018

Mitochondrial abnormalities have been identified as a central mechanism in multiple neurodegenerative diseases and, therefore, the mitochondria have been explored as a therapeutic target. This review will focus on the evidence for mitochondrial abnormalities in the two most common neurodegenerative diseases, Parkinson's disease and Alzheimer's disease. In addition, we discuss the main strategies which have been explored in these diseases to target the mitochondria for therapeutic purposes, focusing on mitochondrially targeted antioxidants, peptides, modulators of mitochondrial dynamics and phenotypic screening outcomes.
Experimental and numerical thermal analysis of open-cell metal foams developed through a topological optimization and 3D printing process
Authors: Merabtine Abdelatif , Gardan Nicolas , Gardan Julien , Badreddine Houssem , Zhang Chuan , Zhu Feng , Gong Xiao-Lu
Published: July 2018

This study focuses on the thermal analysis and comparing a lattice model and an optimized model of open-cell metal foams manufactured thanks to a metal casting process. The topological optimization defines the complex geometry through thermal criteria and a plaster mold reproduces it in 3D printing to be used in casting. The study of the thermal behavior conducted on the two open foam metal structures is performed based on several measurements, as well as numerical simulations. It is observed that the optimized metal foam presented less and non-homogenous local temperature than the lattice model with the gap of about 10 °C between both models. The pore size and porosity significantly affect the heat transfer through the metal foam. The comparison between numerical simulations and experimental results regarding the temperature fields shows a good agreement allowing the validation of the developed three-dimensional model based on the finite element method.
Innovative Lehrmethoden: Einsatz eines ophthalmochirurgischen Wetlabs im Studentenunterricht
Authors: Enders Christian , Schneider Achim , Keis Oliver , Grab-Kroll Claudia , Loidl Max , Kampmeier Jürgen , Lang Gerhard K. , Werner Jens Ulrich
Published: July 2018

Hintergrund Ein erhöhter Bedarf an ärztlichem Nachwuchs in Deutschland führt dazu, dass der Wettbewerb um die besten Köpfe schon während des Studiums beginnt. Daher ist es Aufgabe der Universitätskliniken, ihren Studierenden bestmögliche Lehrveranstaltungen anzubieten, um Interesse am jeweiligen Fachgebiet zu wecken. Wir überprüften deshalb den Einfluss eines ophthalmochirurgischen Wetlabs auf die Lehre im Rahmen des klinischen Studienabschnitts.

Material/Methoden Im Rahmen der Intensivwoche Augenheilkunde an unserer Universitätsklinik wurde den Studierenden die freiwillige Teilnahme an dem ophthalmochirurgischen Wetlab angeboten. Zu Beginn und am Ende der Intensivwoche sowie am Ende des Wetlabs beantworteten die Studierenden Fragebögen mit Fragen zum Interesse an dem Fachgebiet Augenheilkunde sowie der konkreten Bewertung des Wetlabs.

Ergebnisse Das Interesse der Studierenden an der Augenheilkunde konnte durch die Intensivwoche und zusätzlich durch das Wetlab gesteigert werden. Das Wetlab bereicherte die Intensivwoche und wurde von den Teilnehmenden mit der Schulnote 1,12 bewertet. Die Gesamtbewertung der Intensivwoche war unter Teilnehmenden des Wetlabs signifikant besser als in der Gruppe ohne Wetlab-Teilnahme. Das Wetlab bereitete den Studierenden große Freude, ermöglichte das Anwenden des theoretisch erworbenen Wissens, erlaubte wertvolle Einblicke in das Fach Augenheilkunde und war problemlos umsetzbar.

Schlussfolgerung Die Integration eines Wetlabs in die Lehre im klinischen Studienabschnitt wird von den Studierenden sehr positiv bewertet und ermöglicht diesen einen wertvollen Einblick in das Fachgebiet Augenheilkunde sowie in das Berufsfeld des Augenarztes.
Radical-type Reactions Controlled by Cobalt: From Carbene Radical Reactivity to the Catalytic Intermediacy of Reactive o-Quinodimethanes
Authors: de Bruin Bas , te Grotenhuis Colet
Published: July 2018

In this account, we summarize our recent efforts in the fields of ‘open-shell organometallic chemistry’ and ‘metalloradical catalysis’. We focus in particular on the use of so-called ‘carbene radicals’ for the synthesis of a variety of useful synthons for organic chemistry. We further show that unexpected reactivity arises from catalytic synthesis of unusual o-quinone methide and o-quinodimethane intermediates that undergo subsequent rearrangements to uncommon products.

1 Introduction

2 General (Fischer-Type) Carbene and Nitrene Reactivity and Their Relation to Carbene and Nitrene Radical Reactivity

3 Carbene and Nitrene (Radical) Precursors

4 Formation and Intrinsic Radical-Type Reactivity of Carbene and Nitrene Radicals

5 Types of Cobalt Catalysts Used in Reactions Involving Carbene and Nitrene Radicals

6 Applications of Cobalt-Catalyzed Ring-Closure Reactions via ­Carbene Radicals

7 Intermediacy of o-Quinone Methide and o-Quidodimethanes in Carbene Ring-Closing Reactions

8 Conclusion
Diversity of Glycoprotein Deficiencies in Glanzmann’s Thrombasthenia
Authors: Meyer M , Herrmann F H
Published: July 2018

The platelet proteins of 9 thrombasthenic patients from 7 families were analysed by high resolution two-dimensional gel electrophoresis (HR-2DE) and crossed immunoelectrophoresis (CIE). In 7 patients both glycoproteins (GPs) IIb and Ilia were absent or reduced to roughly the same extent. In two related patients only a trace of GP Ilb-IIIa complex was detected in CIE, but HR-2DE revealed a glycopeptide in the position of GP Ilia in an amount comparable to type II thrombasthenia. This GP Ilia-like component was neither recognized normally by anti-GP Ilb-IIIa antibodies nor labeled by surface iodination. In unreduced-reduced two-dimensional gel electrophoresis two components were observed in the region of GP Ilia. The assumption of a structural variant of GP Ilia in the two related patients is discussed.
Turnover Study of Heparin Cofactor II in Healthy Man
Authors: Sié P , Dopouy D , Pichon J , Boneu B
Published: July 2018

Heparin cofactor II (HC II) is a heparin-dependent inhibitor of thrombin, distinct from antithrombin III (AT III). This study was designed to evaluate its metabolism in healthy subjects. Purified HC II was labelled with 125I by the lactoperoxidase-glucose oxidase technique. The biological activity of the HC II was unchanged after labelling as was its migratory pattern by crossed immunoelectrophoresis in the presence of heparin or dermatan sulfate.

Three healthy volunteers were injected with 10 uCi and the plasma radioactivity was measured daily. The data were approximated by a sum of two exponential terms and the metabolism of HC II was described by a two compartment mamillary system.

The mean values of fractional catabolic rate, intravascular fraction and half-life of the elimination phase were respectively: 0.44 d-1, 0.60 and 2.53 d. These parameters are of the same order of magnitude as those reported in the literature for AT III. The plasma HC II concentration in the 3 subjects ranged from 61 to 82 ug/ml as estimated using our purified preparation. Accordingly, the absolute catabolic rate ranged from 1.17 to 1.36 mg · kg-1 · d-1.
Effect of Dextran on Factor Vlll/von Willebrand Factor Structure and Function
Authors: Batlle J , del Río F , López Fernández M F , Martín R , López Borrasca A
Published: July 2018

Factor VIII/von Willebrand factor was analyzed before and after the infusion of 500 ml of Dextran 70 to normal volunteers. Factor VIII procoagulant activity, factor VIII related antigen and ristocetin cofactor activity showed a significant decrease, reaching after six hours the minimum level, which did not correlate with the hemodilution effect caused by dextran. Ristocetin-induced platelet agglutination (RIPA) in volunteers’ platelet-rich plasma (PRP) did not show any significant change between preinfusion time and six hours after the infusion. Multimeric analysis of von Willebrand factor (vWF) showed a progressive decrease of all the multimers which was more pronounced in the largest multimers. No change was seen in the “triplet” structure of vWF. No effect was noticed when dextran was incubated “in vitro” either with PRP or platelet-poor plasma. The modification induced by dextran is close to the pattern seen in subtype Ib von Willebrand’s disease.
The Dilute Phospholipid APTT: A Sensitive Assay for Verification of Lupus Anticoagulants
Authors: Alving Barbara M , Baldwin Phillip E , Richards Roberta L , Jackson Beverly J
Published: July 2018

A simple sensitive method for verification of lupus anticoagulants utilizing dilution of phospholipid in the activated partial thromboplastin time (APTT) system is described. Patient plasma, mixed with an equal volume of normal plasma, is activated with micronized silica. To this mixture are added different dilutions of Thrombofax® and then calcium chloride. Clotting times are plotted linearly against the logarithm of the phospholipid dilutions and slopes are calculated by regression analysis. In this assay the mean negative slope of 19 plasmas that contained antiphospholipid activity was five times greater than those of normal plasma or those obtained from patients having single or multiple coagulation factor deficiencies such as those induced by warfarin. The assay can be modified to test heparinized plasmas. Thus, it is a sensitive means by which to verify the presence of lupus anticoagulants in patients who have congenital or acquired factor deficiencies or who are receiving anticoagulant therapy.
Management of Haemophilia A with Antibodies - The Effect of Combined Treatment with Factor VIII, Hydrocortisone and Cyclophosphamide
Authors: Hedner U , Tengborn L
Published: July 2018

Immune tolerance has by several methods been induced in
haemophiliacs with antibodies. A conversion of “high responders” into “low responders” was previously reported after repeated moderate factor IX doses over periods of 7-10 days in
combination with cyclophosphamide and steroids in two patients with haemophilia B and inhibitors. This paper reports similar results in a heamophilia A patient by giving factor VIII, cyclophosphamide, and steroids during relatively short periods of time (7-8 days). The anamnestic response markedly decreased already following the first treatment and never exceeded a level of 1 u/ml (˜ 3 BU/ml) even when boosted with ordinary factor VIII doses for only 3 days. It is concluded that the markedly decreased secondary antibody response is most probably the result of factor VIII given at short intervals (twice a day) for periods of up to about one week when given in combination with cyclophosphamide and steroids. The same effect may be achieved by other methods. The treatment schedule suggested in the present paper is, however, simple and avoids long periods of high antibody levels. Furthermore, the total factor VIII dose used is lower than suggested in most other treatment schedules, which makes the treatment substantially less expensive.
Effect of Imidazoline Drugs on Human Blood Platelet Aggregation
Authors: Petrusewicz Jacek , Kaliszan Roman
Published: July 2018

The effect of seven commonly used in therapy imidazoline derivatives on human blood platelet aggregation was studied. Three of the agents, i.e. clonidine, antazoline and tetryzoline were classified as partial agonists of the receptor responsible for aggregation. Two other drugs, i.e. phentolamine and tolazoline act as competitive antagonists of relatively high receptor affinity. The remaining imidazolines: xylometazoline and naphazoline effectively inhibit the platelet receptor in a non-competitive manner. The last two compounds seem to be selective alpha2-adrenoceptor antagonists.
Effects of Ticlopidine of Platelet Function in Men with Stable Angina Pectoris
Authors: Berglund Ulf , Schenck Henning von , Wallentin Lars
Published: July 2018

The effects of ticlopidine (T) (500 mg daily) on platelet function were investigated in a double-blind placebo-controlled study in 38 middle-aged men with stable incapacitating angina pectoris. The in vitro platelet reactivity to aggregating agents, the platelet sensitivity to prostacyclin and the plasma levels of platelet specific proteins and fibrinogen were determined before and after 4 and 8 weeks of treatment. T exerted a potent inhibitory effect on ADP- and collagen-induced platelet aggregation. The effect of T was proportional to the pretreatment reactivity to ADP and collagen. The inhibitory effect of T on the epinephrine response was less pronounced. The plasma levels of beta-thromboglobulin, platelet factor 4 and fibrinogen were not influenced by T. The platelet inhibition of prostacyclin was potentiated by T, and it was demonstrated that T and prostacyclin had synergistic inhibitory effects on platelet aggregation.
The Effect of Pentosan Polysulphate (SP54) on the Fibrinolytic Enzyme System - A Human Volunteer and Experimental Animal Study
Authors: Marsh N A , Peyser P M , Creighton L J , Mahmoud M , Gaffney P J
Published: July 2018

Pentosan polysulphate causes an increase in plasminogen activator activity in plasma both after oral ingestion and after subcutaneous injection. The effect is greatest after 3 h and has disappeared by 6 h. Repeat doses by mouth over 5 days elicit a similar response. The recorded increase in activity is due largely to the release of tissue-type plasminogen activator (tPA) from the endothelium according to the antigen assay although there could be a small contribution from Factor XH-related “intrinsic” fibrinolysis induced in vitro. SP54 enhances activity ex vivo by a non-specific surface effect, and this phenomenon may contribute the increased levels of activity seen in vitro. Administration of SP54 to animals elicits a similar increase in activator activity, the intramuscular route being slightly more effective. Results with an inferior vena cava thrombosis model in the rat suggest that pentosan polysulphate may induce a thrombolytic effect.
Heparin Small Pool High Yield Purified Factor VIII: In Vivo Recovery and Half-Life of Routinely Produced Freeze-Dried Concentrate
Authors: Sibinga C T Smit , Daenen S M G J , Imhoff G W van , Maas A , Das P C
Published: July 2018

New approaches and techniques for improving source material collection and Factor VIII production at Blood Bank level have been reported recently.

Heparin has been shown to be of importance in increasing yields and stability of FVIII in the purification and concentration process. Work has been done to develop on a routine scale the heparin double cold precipitation technique for the production of a freeze-dried high yield purified FVIII concentrate.

The product has been tested clinically in 4 severe hemophilia A patients for recovery, half-life and acute side-effects, using two dosages over 8 infusions. There was no significant difference between the two dosages. Mean recovery 99.1% and mean halflife 8 hr, ranging from 6.5 to 10.3 hr.

No side-effects were observed.

These results justify further exploration of the potential of heparin for high yield purified FVIII production.
The Interaction of Immobilized Thrombin with Human Antithrombin III
Authors: Marciniak E , Gora-Maslak G
Published: July 2018

Interaction of human antithrombin III (AT III) with human α-thrombin coupled to Sepharose 4B was investigated. Despite markedly reduced esterolytic, amidolytic and especially coagulant activity, more than 90% of immobilized thrombin formed stable complexes with purified AT III. Presence of high affinity heparin did not facilitate the inhibition to the degree seen in reactions conducted with soluble thrombin. Instead, heparin induced proteolysis of up to 66% of the inhibitor that remained in solution. This led to the isolation of a homogeneous protein fragment which migrated in SDS-gel electrophoresis as a band of 50,000 Mr, cross-reacted with antibodies to human AT III but showed no biologic activity nor sufficient affinity for heparin. Out of the three major inhibitors capable of binding soluble thrombin in human plasma, only AT III reacted with immobilized thrombin. However, Sepharose-coupled thrombin mixed with plasma in the presence of heparin produced outstanding quantities of residual immunoreactive AT III devoid of inhibitory activity. These data suggest that presence of high affinity heparin in the environment of thrombin attached to a solid support may dramatically decrease the efficiency of enzyme inhibition.
Dysfunctional Plasminogen in Full Term Newborn - Study of Active Site of Plasmin
Authors: Benavent A , Estellés A , Aznar J , Martinez-Sales V , Gilabert J , Fornas E
Published: July 2018

The functional activity and active site of plasmin in full-term newborns have been studied and compared to those in adults in order to investigate the nature of the abnormality found in newborn plasminogen descried in a previous paper.

The functional activity of newborn plasminogen measured on chromogenic substrate was approximately 18% that of adult plasminogen when streptokinase was used as an activator and 12% when urokinase was used.

Proteolysis of newborn plasminogen by urokinase yielding a two-chain plasmin form occurred normally, but the incorporation of diisopropylphosphorofluoridate into the light chain of newborn plasmin was approximately 23% of that observed in the light chain of adult plasmin.

These observations suggest that the abnormality of full-term newborn plasminogen is located in the active site of the molecule.
Stanozolol-Induced Changes in Fibrinolysis and Coagulation in Healthy Adults
Authors: Kluft C , Preston F E , Malia R G , Bertina R M , Wijngaards G , Greaves M , Verheijen J H , Dooijewaard G
Published: July 2018

The effects of orally-administered stanozolol, 5 mg b. d. on fibrinolysis, coagulation and on various haematological and biochemical parameters have been studied in 16 healthy adults, 8 males and 8 females. Statistically significant enhancement of extrinsic (tissue-type) plasminogen activator activity was detected in all subjects studied. This was associated with significant increases in plasma plasminogen and a concomitant reduction in histidine-rich glycoprotein. There were no changes in plasma urokinase activity. Changes in the coagulation system included significant reduction in plasma fibrinogen and elevation of protein C and anti thrombin III. Changes in plasma lipids included significant reduction of HDL cholesterol associated with an increase in LDL triglycerides. No change occurred in total cholesterol. There were no major differences between the sexes, nor were there serious side effects.

The effects of stanozolol on extrinsic (tissue-type) plasminogen activator activity, “free” plasminogen, protein C and antithrombin III, argue strongly in favour of its therapeutic potential.
The Importance of Corticoids Added to Continued Treatment with Factor VIII Concentrates in the Suppression of Inhibitors in Haemophilia A
Authors: Aznar J A , Jorquera J I , Peiró A , Garcia I
Published: July 2018

A protocol is presented to suppress inhibitors in haemophilia A using continued treatment with f. VIII (50 U/kg b.w./day) and fluprednisolone (0.5 mg/kg b.w., for 21 days) until reaching correct in vivo recovery after therapeutic administration.

5 high responder patients were treated whose inhibitors were detected at least 2 years before beginning the treatment. The inhibitors were eradicated in 4 patients using continued treatment for between 4 and 24 months. Patient 1 was treated exclusively with factor and the others also with corticoids when the level was 0 B.U. (or 20 B.U., patient 4). The patients began tri-weekly prophylactic treatment and rehabilitation exercises after recovery test normalization. After progressive reduction of the prophylactic treatment they started on demand treatment. After more than 5 months of this treatment no anamnestic response has been detected in any patient, in spite of several factor VIII administrations.
Evidence that von Willebrand Factor is Not Required for the Clotting of Plasma in the Presence of Platelets and Kaolin (Hardisty-Hutton Test)
Authors: McPherson Jean , Soberano Mercedes E , Macdonald Cheryl , Zucker Marjorie B
Published: July 2018

Antihemophilic factor (AHF) essentially free of von Willebrand factor (vWF) was used to determine whether vWF affected the coagulant activity of AHF in a kaolin-activated system using platelet-rich plasma. The AHF was prepared by sequential chromatography on solid-phase polyelectrolyte (PE E-5), and on Sepharose CL-4B in the presence of a high concentration of CaCl2. Residual traces of vWF antigen were removed by affinity chromatography with immobilized anti-vWF IgG. The essentially vWF-free AHF corrected the clotting defect of plasma from three patients with severe von Willebrand’s disease (vWD) as measured by the kaolin-activated clotting time in the presence of normal or vWD platelets (Hardisty-Hutton test). Addition of hemophilic plasma as a source of vWF did not cause additional improvement, nor did a potent antibody to vWF raised in rabbits inhibit the ability of AHF to shorten the clotting time of vWD plasma. Thus we found no evidence that vWF is necessary for AHF to function in the coagulation of recalcified kaolin-activated vWF-deficient platelet-rich plasma.
A Double-Blind Trial of Ticlopidine in Sickle Cell Disease
Authors: Semple M J , Al-Hasani S F , Kioy P , Savidge G F
Published: July 2018

Baseline studies of 111indium oxine labelled platelet life-span, platelet α-granule release products, β-thromboglobulin (βTG) and platelet factor 4 (PF4), and factor VIII related activities were performed on 9 asymptomatic patients with sickle cell disease, who were subsequently randomised in a prospective double-blind trial of ticlopidine (250 mg. b. d.) or placebo for one month and the investigations repeated. Control studies indicated that 5 of the 9 patients had shortened platelet survivals: mean βTG (50.8 ng/ ml) and PF4 (19.5 ng/ml), factor VIII: C (283.4 i. u./dl) and factor VIIIR: AG (168.7 u/dl) levels were raised. Ticlopidine treatment did not significantly improve platelet life-span or factor VIII levels, though it was associated with reduced values of βTG and PF4. One patient taking ticlopidine developed an infarctive sickle crisis. Although ticlopidine blocked platelet activation, this alone did not improve platelet survival or prevent sickle crisis: in view of evidence of platelet activation in sickle cell disease, however, a longer trial of prophylactic antiplatelet drugs might be warranted.
Effect of Vitamin E on Platelet Aggregation in Diabetes Mellitus
Authors: Watanabe J , Umeda F , Wakasugi H , Ibayashi H
Published: July 2018

Vitamin E is known to be an inhibitor of platelet prostaglandin production and aggregation. The rate of platelet aggregation induced by adenosine diphosphate was significantly increased in diabetics with proliferative retinopathy and the enhanced production of thromboxane B2, a stable metabolite of thromboxane A2, was demonstrated in those patients. On the other hand, vitamin E in platelets was significantly reduced in diabetics compared with age matched controls. In addition, it was shown that vitamin E content in platelets examined in diabetic and control subjects inversely correlated with both the rate of platelet aggregation and thromboxane B2 production during aggregation. It is suggested that the reduced vitamin E levels in diabetic platelets can contribute to the mechanisms of the enhanced platelet thromboxane production and aggregation which relate to the development of vascular complications.
Correction of Clotting Factor “Deficiencies” in Plasma from Patients with Lupus-Like Anticoagulants
Authors: Clyne Lionel P , Honig Christine L , Dainiak Nicholas
Published: July 2018

Identification of spurious coagulation factor deficiencies that are known to occur in association with lupus-like anticoagulants (LLACs) requires the use of cumbersome laboratory procedures. To determine whether single-stage assays employing the APTT system may be used to identify such artifacts, we measured multiple clotting factor levels by several techniques in plasma of six patients with typical LLACs. While normal activities of factors VIII, IX, XI and XII were measured in only 4/24 APTT assays (17%) employing human plasma substrate, normal factor activities were present in all 24 APTT assays employing bovine, canine or rabbit plasma substrate. Normal factor II, V and X activities were recorded in all but one case in assays that utilized a modified Stypven time, while normal factor VIII levels were determined in 5/6 plasmas when the thromboplastin generation test was employed. These results indicate that the use of heterologous plasma substrates in the APTT system may provide a simple method to identify such coagulation factor “deficiencies”.