bluuebunny/crossref_metadata_2025 huggingface dataset:
Adsorption behavior of carboxymethyl guar gum onto quartz sand
Authors: Yin Zichen , Wang Yanling , Zeng Yijin
Published: August 2018

The adsorption of carboxymethyl guar gum on quartz sand was studied quantitatively and the factors influencing adsorption were investigated.
Crystal structural design of exposed planes: express channels, high-rate capability cathodes for lithium-ion batteries
Authors: Zhou Shiyuan , Mei Tao , Wang Xianbao , Qian Yitai
Published: August 2018

The rational design of crystal planes with express channels is an effective approach to develop the high-performance cathodes for lithium ion batteries.
Flexible multi-wavelength photodetector based on porous silicon nanowires
Authors: Kim Do Hoon , Lee Woong , Myoung Jae-Min
Published: August 2018

A flexible multi-wavelength photodetector based on PSi NWs was designed and their fast photoresponse property to all the RGB spectra was confirmed.
Interaction of nanodiamonds with bacteria
Authors: Ong S. Y. , van Harmelen R. J. J. , Norouzi N. , Offens F. , Venema I. M. , Habibi Najafi M. B. , Schirhagl R.
Published: August 2018

Fluorescent nanodiamonds have excellent biocompatibility. For bacteria we find bacteriostatic activity or even promotion of growth depending on the conditions.
Exploring the potential of phosphotriazole 5′ mRNA cap analogues as efficient translation initiators
Authors: Walczak Sylwia , Sikorski Pawel J. , Kasprzyk Renata , Kowalska Joanna , Jemielity Jacek
Published: August 2018

New phosphotriazole cap analogues proved to enhance translationin vitroandin vivomaking them applicable in the design of RNA with increased translational potential.
Phosphine-mediated partial reduction of alkynes to form both (E)- and (Z)-alkenes
Authors: Pierce Brett M. , Simpson Brittany F. , Ferguson Kane H. , Whittaker Rachel E.
Published: August 2018

A mild, tunable method to form both (E)- and (Z)-alkenes from alkynes is reported using PPh3 as a reductant.
Enhancement of intra- and inter-molecular π-conjugated effects for a non-fullerene acceptor to achieve high-efficiency organic solar cells with an extended photoresponse range and optimized morphology
Authors: Wang Ning , Zhan Lingling , Li Shuixing , Shi Minmin , Lau Tsz-Ki , Lu Xinhui , Shikler Rafi , Li Chang-Zhi , Chen Hongzheng
Published: August 2018

The extended π-conjugation of DF-PCNC leads to higher PCE andJSCfor the resultant OSCs.
Janus nanocarriers for magnetically targeted and hyperthermia-enhanced curcumin therapy of liver cancer
Authors: Xing Hao , Wang Zheng , Shao Dan , Chang Zhimin , Ge Mingfeng , Li Li , Wu Mingdi , Yan Zhuangzhi , Dong Wenfei
Published: August 2018

Curcumin is regarded as a promising chemotherapeutic agent due to its anti-cancer activity and excellent biosafety.
Hypoglycemic, hypolipidemic and antioxidant effects of iridoid glycosides extracted from Corni fructus: possible involvement of the PI3K–Akt/PKB signaling pathway
Authors: Kang Jiefang , Guo Chen , Thome Rodolfo , Yang Ning , Zhang Yuan , Li Xing , Cao Xiaoyan
Published: August 2018

Iridoid glycosides (CIG) are the major component of Corni fructus.
Exploring the binding mechanisms of PDE5 with chromeno[2,3-c]pyrrol-9(2H)-one by theoretical approaches
Authors: Huang Xianfeng , Xu Peng , Cao Yijing , Liu Li , Song Guoqiang , Xu Lei
Published: August 2018

Cyclic nucleotide phosphodiesterase type 5 (PDE5) is exclusively specific for the cyclic guanosine monophosphate (cGMP), and PDE5 is an important drug target for the treatment of erectile dysfunction and pulmonary arterial hypertension (PAH).
A chemical reporter facilitates the detection and identification of lysine HMGylation on histones
Authors: Bao Xiucong , Xiong Ying , Li Xin , Li Xiang David
Published: August 2018

Chemical reporter, HMGAM-yne, facilitates the detection and identification of lysine HMGylation on histones.
Copper catalyzed photoredox synthesis of α-keto esters, quinoxaline, and naphthoquinone: controlled oxidation of terminal alkynes to glyoxals
Authors: Das Deb Kumar , Kumar Pampana V. Kishore , Hwang Kuo Chu
Published: August 2018

Controlled oxidation of the terminal CC triple bond using O2 (1 atm) as an oxidant and reagent.
Thermophoretic forces on a mesoscopic scale
Authors: Burelbach Jérôme , Brückner David B. , Frenkel Daan , Eiser Erika
Published: August 2018

We present measurements of thermophoretic forces on a colloid that comply with a hydrodynamic reciprocal approach to thermophoresis.
A vertically channeled lamellar membrane for molecular sieving of water from organic solvents
Authors: Li Xiaoting , Wang Naixin , Huang Zheng , Zhang Lilong , Xie Ya-Bo , An Quan-Fu , Ji Shulan
Published: August 2018

A vertically channeled layered double hydroxides membrane was prepared for molecular sieving.
Crystallographic orientation–surface energy–wetting property relationships of rare earth oxides
Authors: Tam Jason , Feng Bin , Ikuhara Yuichi , Ohta Hiromichi , Erb Uwe
Published: August 2018

Understanding the wettability of rare earth oxide ceramics from crystallographic orientation–surface energy relationships.
NiVO3 fused oxide nanoparticles – an electrochemically stable intercalation anode material for lithium ion batteries
Authors: McNulty David , Collins Gillian , O'Dwyer Colm
Published: August 2018

For oxides, especially as lithium-ion battery anodes, it is important to engineer the material not only to improve the kinetics of reversible lithiation efficiency but also to avoid capacity and voltage fading, and side reactions, from conversion mode processes that can sometimes occur in tandem with intercalation.
Hollow metallic 1T MoS2 arrays grown on carbon cloth: a freestanding electrode for sodium ion batteries
Authors: Tang Wang-jia , Wang Xiu-li , Xie Dong , Xia Xin-hui , Gu Chang-dong , Tu Jiang-ping
Published: August 2018

We have synthesized hollow metallic 1T MoS2 arrays on carbon cloth and tested their electrochemical performance in sodium ion batteries.
Resurgence of DSCs with copper electrolyte: a detailed investigation of interfacial charge dynamics with cobalt and iodine based electrolytes
Authors: Pradhan Sourava C. , Hagfeldt Anders , Soman Suraj
Published: August 2018

Deploying earth abundant copper as a redox mediator in dye-sensitized solar cells (DSCs) has been found to be a very promising strategy to achieve higher photovoltage and power conversion efficiencies in full sun (100 mW cm−2) and in low/diffuse light conditions.
Directly printed wearable electronic sensing textiles towards human–machine interfaces
Authors: Liao Xinqin , Song Weitao , Zhang Xiangyu , Huang Hua , Wang Yongtian , Zheng Yuanjin
Published: August 2018

An intelligent glove assembled with stencil printed and ultrasensitive textile strain sensors was prepared for wireless gesture control.
High triplet energy exciplex host derived from a CN modified carbazole based n-type host for improved efficiency and lifetime in blue phosphorescent organic light-emitting diodes
Authors: Shin Su Kyeong , Han Si Hyun , Lee Jun Yeob
Published: August 2018

High triplet energy exciplexes which can improve the lifetime of blue phosphorescent organic light-emitting diodes were developed by mixing a carbazole based hole transport type host with a CN modified carbazole based electron transport type host.
Cross‐pol long‐cable transponder for bistatic ground‐based synthetic aperture radar
Authors: Pieraccini M. , Miccinesi L.
Published: August 2018

A transponder consisting of two antennas and an amplifier allows a ground‐based synthetic aperture radar to operate as a bistatic system. In such a way, it is able to detect two displacement components of targets in its field of view. An enhanced transponder is proposed. Its special features are (i) cross‐polarised antennas and (ii) antennas separated by a long RF cable (35 m). This transponder is able to provide 82 dB gain without triggering auto‐oscillations. Monostatic and bistatic images have been obtained in an urban scenario.
Fast and accurate vision‐based stereo reconstruction and motion estimation for image‐guided liver surgery
Authors: Speers Andrew D. , Ma Burton , Jarnagin William R. , Himidan Sharifa , Simpson Amber L. , Wildes Richard P.
Published: August 2018

Image‐guided liver surgery aims to enhance the precision of resection and ablation by providing fast localisation of tumours and adjacent complex vasculature to improve oncologic outcome. This Letter presents a novel end‐to‐end solution for fast stereo reconstruction and motion estimation that demonstrates high accuracy with phantom and clinical data. The authors’ computationally efficient coarse‐to‐fine (CTF) stereo approach facilitates liver imaging by accounting for low texture regions, enabling precise three‐dimensional (3D) boundary recovery through the use of adaptive windows and utilising a robust 3D motion estimator to reject spurious data. To the best of their knowledge, theirs is the only adaptive CTF matching approach to reconstruction and motion estimation that registers time series of reconstructions to a single key frame for registration to a volumetric computed tomography scan. The system is evaluated empirically in controlled laboratory experiments with a liver phantom and motorised stages for precise quantitative evaluation. Additional evaluation is provided through testing with patient data during liver resection.
Autonomous‐driving vehicle test technology based on virtual reality
Authors: Yao Shouwen , Zhang Jiahao , Hu Ziran , Wang Yu , Zhou Xilin
Published: August 2018

In order to mitigate risks from road tests for autonomous‐driving vehicles, reduce costs and accelerate development, a virtual reality (VR)‐based test platform for autonomous‐driving vehicles was built combined with the AirSim system and the UE4 engine by establishing a model library which contains the vehicle dynamics model, sensor models and traffic environment model. The controller‐in‐the‐loop simulation method was implemented to complete the simulation test for autonomous vehicles under different driving conditions and the simulation results were used to optimise the autonomous‐driving control system. The actual autonomous driving road test can now be done in an immersive VR simulation environment where autonomous‐driving road‐testing is done safely and cost‐effectively. This plays a significant role in the future development of autonomous‐driving vehicles.
Konservative Therapiemöglichkeiten bei Osteoporose und osteoporosebedingten Gestaltveränderungen
Authors: Regenspurger Katja , Delank Karl-Stefan
Published: August 2018

Osteoporosebedingte Beschwerden resultieren zum einen aus frischen Wirbelkörperfrakturen und zum anderen aus typischen osteoporotischen Gestaltveränderungen mit zunehmender thorakaler Kyphosierung, Körperlotventralisation und Verschlechterung der posturalen Stabilität. Daraus resultieren Gangstörungen und eine erhöhte Sturzgefährdung. Statische Veränderungen bedingen zudem Veränderungen der Muskelaktivierung mit daraus resultierenden Funktionsstörungen. Zusätzlich besteht eine enge altersbedingte Korrelation zwischen dem Auftreten einer Osteoporose und einer Sarkopenie. Im konservativen Management osteoporosebedingter Beschwerden stehen im Falle von frischen Frakturen die rasche Schmerzlinderung und die schnellstmögliche Mobilisation im Fokus der Bemühungen. Das Management chronischer Schmerzen und funktioneller Defizite erfordert eine multimodale Vorgehensweise mit Bewegungstherapie und Krafttraining mit besonderem Fokus auf posturaler Stabilität, auch als Ganzkörpervibrationstraining, manueller Therapie und physikalischen und medikamentösen Maßnahmen der Schmerztherapie unter Beachtung von biopsychosozialen Zusammenhängen.
Ramadan Observance during Pregnancy in Germany: a Challenge for Prenatal Care
Authors: Leimer Birgit , Pradella Fabienne , Fruth Anja , Queißer Annette , van Ewijk Reyn
Published: August 2018

Introduction Fasting during Ramadan while pregnant has been shown to have long-term negative effects on the offspringʼs physical and cognitive health. Even though most Muslims do not believe pregnant women are obligated to fast during Ramadan, fasting rates of up to 87% have been reported for pregnant women. No data exists to date about Ramadan adherence and behavior in Germany.

Methods The Mainz Study of Ramadan and Pregnancy surveyed pregnant Muslims and new Muslim mothers in Mainz between October 2016 and January 2017 and collected information on Ramadan adherence and behavior. We also collected data on personal characteristics and opinions, to identify determinants of fasting using statistical analysis.

Results We found that 43% of pregnant Muslim women fasted at least one day during Ramadan 2016. Women who fasted were significantly younger and less educated. There was no significant difference in terms of country of origin between those women who fasted and those who did not. Only 49% of women who fasted and 38% of women who did not fast discussed their Ramadan behavior with their doctor. Less than 2% of women reported being proactively approached by their doctor.

Conclusion To ensure that pregnant Muslim women living in Germany can make their fasting decision based on objective information, it is necessary to raise awareness about Ramadan fasting during pregnancy among medical professionals in Germany.
A Novel Technique for Mapping the Vascularity of Labia Minora Prior to Labiaplasty: Cold Light Illumination
Authors: Kaya Aski , Dogan Ozan , Yassa Murat , Basbug Alper , Çalışkan Eray
Published: August 2018

Objective Aim of the study was to assess the feasibility of a novel technique to determine the vascularity of labia minora prior to labiaplasty.

Methods A cold light source employed in laparoscopic procedures was used to illuminate the outer surface of the labia minora as described in this prospective descriptive study.

Results Of the patients, 46.1% (n = 41) had upper third prominence, 36% (n = 32) had middle third prominence, and 18% (n = 16) had lower third prominence according to the Banwell classification of morphologies. Right labia minora width was 0 – 2 cm in 51.7% (n = 46), 2 – 4 cm in 47.2% (n = 42) and > 4 cm in 1.1% (n = 1) of cases. Left labia minora width was 0 – 2 cm in 52.8% (n = 47), 2 – 4 cm in 41.6% (n = 37) and > 4 cm in 5.6% (n = 5) of cases. The incidence of Anterior 2 and Posterior 1 vessels in the different morphologies were statistically significantly different (p = 0.007, p = 0.018). The Anterior 2 vessel was higher in the lower morphology group whereas the Posterior 1 vessel was higher in the upper morphology group. A central vessel was observed in 93.3% (n = 83) of patients in the left labium minus and the right labium minus. The incidence of the Posterior 1 vessel was significantly higher in the left labium minus than in the right labium minus (p = 0.021).

Discussion This novel technique to assess labial vascularity using a cold light source could be very useful to reduce dehiscence by avoiding excessive resection of highly vascularized tissue. Most units can easily access a cold light source, which can be used to assess labial vascularity prior to labiaplasty.
The impact of endoscopic ultrasound-guided fine-needle aspiration of lymph nodes on subsequent positron emission tomography/computed tomography imaging: a prospective study
Authors: Bjerring Ole , Hess Søren , Fristrup Claus , Høilund-Carlsen Poul , Mortensen Michael
Published: August 2018

Background Modern cancer diagnostic work-up is based on multiple modalities within a short
time period. The interplay between these modalities is complex and not well known. Performing biopsy procedures prior to (18)F-2-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography/computed tomography (PET/CT) is considered to pose a risk of false-positive imaging results; however, this is not based on solid scientific evidence. The use of endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA) is commonly used in upper gastrointestinal malignancies, is proven safe, and has very little risk of complications. This study aimed to assess whether EUS-FNA induces inflammation that would increase FDG uptake on subsequent PET/CT.

Methods 27 patients who were referred for upper gastrointestinal EUS for different reasons initially underwent FDG-PET/CT to detect biopsy-eligible lymph nodes with no FDG uptake. Patients then underwent EUS-FNA of the benign lymph nodes, with a minimum of three passes. Patients were re-evaluated with FDG-PET/CT 1 week later, with specific emphasis on the biopsied lymph nodes.

Results None of the biopsied lymph nodes showed increased FDG uptake on follow-up FDG-PET/CT. No adverse events occurred.

Conclusion EUS-FNA prior to FDG-PET/CT did not lead to false-positive FDG uptake. The interpretive impact of minor procedures prior to FDG-PET/CT needs to be re-evaluated.
A 21st Century Embarrassment of Riches: The Balance Between Health Data Access, Usage, and Sharing
Authors: Holmes John , Soualmia Lina , Séroussi Brigitte
Published: August 2018

Objectives: To provide an introduction to the 2018 International Medical Informatics Association (IMIA) Yearbook by the editors.

Methods: This editorial provides an overview and introduction to the 2018 IMIA Yearbook which special topic is: “Between access and privacy: Challenges in sharing health data”. The special topic editors and section are discussed, and the new section of the 2018 Yearbook, Cancer Informatics, is introduced. Changes in the Yearbook editorial team are also described.

Results: With the exponential burgeoning of health-related data, and attendant demands for sharing and using these data, the special topic for 2018 is noteworthy for its timeliness. Data sharing brings responsibility for preservation of data privacy, and for this, patient perspectives are of paramount importance in understanding how patients view their health data and how their privacy should be protected.

Conclusion: With the increase in availability of health-related data from many different sources and contexts, there is an urgent need for informaticians to become aware of their role in maintaining the balance between data sharing and privacy.
Visions for IAHSI, the International Academy of Health Sciences Informatics
Authors: Haux Reinhold
Published: August 2018

These visions for IAHSI, the newly founded International Academy of Health Sciences Informatics (“the Academy”), include the following principles, in order of descending priority: (1) The Academy should attempt to contribute to the health of the people in our world, (2) the Academy should be engaged in advising governments and organizations on developing health and science through informatics, (3) the Academy should stimulate progress in informatics research, education, and practice, (4) Academy members should share and exchange knowledge, (5) the Academy's structure and organization should follow the tradition of scientific societies, (6) Academy membership is one of the highest honors in informatics internationally, (7) the Academy should meet where the International Medical Informatics Association meets, and (8) the Academy's structure and organization should be lean and unbiased. These visions have been put forward for discussion specifically but not exclusively to the inaugural class of the Academy, organized at the 2018 Medical Informatics Europe conference, with its distinguished members.
Consumer Health Informatics Adoption among Underserved Populations: Thinking beyond the Digital Divide
Authors: Huh Jina , Koola Jejo , Contreras Alejandro , Castillo Alanah , Ruiz Melissa , Tedone Keely , Yakuta Melissa , Schiaffino Melody
Published: August 2018

Objectives: Underserved populations can benefit from consumer health informatics (CHI) that promotes self-management at a lower cost. However, prior literature suggested that the digital divide and low motivation constituted barriers to CHI adoption. Despite increased Internet use, underserved populations continue to show slow CHI uptake. The aim of the paper is to revisit barriers and facilitators that may impact CHI adoption among underserved populations.

Methods: We surveyed the past five years of literature. We searched PubMed for articles published between 2012 and 2017 that describe empirical evaluations involving CHI use by underserved populations. We abstracted and summarized data about facilitators and barriers impacting CHI adoption.

Results: From 645 search results, after abstract and full-text screening, 13 publications met the inclusion criteria of identifying barriers to and facilitators of underserved populations' CHI adoption. Contrary to earlier literature, the studies suggested that the motivation to improve health literacy and adopt technology was high among studied populations. Beyond the digital divide, barriers included: low health and computer literacy, challenges in accepting the presented information, poor usability, and unclear content. Factors associated with increased use were: user needs for information, user-access mediated by a proxy person, and early user engagement in system design.

Conclusions: While the digital divide remains a barrier, newer studies show that high motivation for CHI use exists. However, simply gaining access to technology is not sufficient to improve adoption unless CHI technology is tailored to address user needs. Future interventions should consider building larger empirical evidence on identifying CHI barriers and facilitators.
ISOLATION AND FUNCTIONAL PROPERTIES OF MONOMERIC BLOOD COAGULATION FACTOR XI
Authors: Berrettini M , Heeb M J , Griffin J H
Published: August 2018

To evaluate the significance of the normal dimeric structure (160,000 MW) of blood coagulation Factor XI (F.XI), a monomeric form (80,000 MW) was produced by mild reduction and alkylation of native F.XI. Since initial efforts to reduce and alkylate F.XI in solution inactivated the molecule, F.XI was bound to high MW kininogen (HMWK) to stabilize the native structure. Purified F.XI was bound to HMWK-Sepharose, and the column was washed for 2 h with 40 μM dithiothreitol in 4mM acetate buffer, 2mM EDTA, 1mM benzamidine, pH 7.8, and then for 2 h with 50 μM iodoacetamide in the same buffer. Elution with 0.5 M NaCl gave a preparation containing ∼ 85% F.XI monomer and ∼ 15% dimer, as judged by nonreduced SDS-PAGE and by gel filtration of the radiolabeled preparation. The monomeric F.XI preparation had only 10% of the clotting activity of dimeric F.XI (per mole of enzymatic site) as measured in APTT clotting assays using F.XI deficient plasma. After activation with β-Factor XIIa in solution, the monomer F.XIa preparation exhibited 85% of the clotting activity of native F.XIa in unactivated PTT assays using F.XI deficient plasma. In addition, when compared to native F.XIa, monomeric F.XIa gave 65% amidolytic activity against the substrate, S-2366, and 75% activity against Factor IX in assays of the release of the activation peptide from 3H-Factor IX. Polystyrene tubes were coated with HMWK then blocked with 1% BSA to study the binding of 125I-F.XI to HWMK. When the binding of the 125I-labeled preparations of monomeric and dimeric forms of F.XI to HMWK was studied, two distinct components were identified in the association of dimeric F.XI, one with high affinity (Kd ∼ 2.5 X 10-9M) and one with less affinity (Kd ∼ 1.7 X 10-8M), while the binding of monomeric F.XI occurred with a single low affinity component (Kd ∼ 1.1 X 10-8M). These observations suggest that the dimeric structure of F.XI is required for efficient binding of the molecule to HMWK and for normal activation by the contact activation system in plasma, but that the dimeric structure of F.XIa does not play a role in the expression of the enzymatic activity against Factor IX in fluid phase.
THE REGULATION OF FACTOR XIa ACTIVITY BY PLATELETS AND ALPHA-1-PROTEASE INHIBITOR
Authors: Walsh P N , Sinha D , Kueppers F , Seaman F S , Blanketein K B
Published: August 2018

Since activated platelets bind factor XI (FXI), FXIa and high molecular weight kininogen (HMWK), promote the proteolytic activation of FXI, release an inhibitor of FXIa, and may protect FXIa from inactivation by plasma protease inhibitors, we have studied the complex interrelationships between platelets, FXIa, alpha-l-protease inhibitor (α1PI) and F-IX activation. Purified FXIa was incubated in the presence or absence of thrombin-treated gel-filtered platelets (GFP) or a platelet releasate and FXIa activity assayed by the release of a H-labeled activation peptide from H-FIX. Our results confirm the report of Soons et al (Blood 68:140, 1986) that platelets secrete an inhibitor of FXIa (PXIaI). The presence of intact GFP partially protected FXIa from inactivation by the PXIaI. The presence of GFP also partially protected FXIa from inactivation in the presence of both α1PI and the PXIaI. Purified HMWK had no effect on FXIa inactivation by α1PI or by the PXIaI. Both platelet-bound FXIa and unbound FXIa in the presence of thrombin-activated platelets were protected from inactivation by α1PI. Thrombin-treated GFP had no effect on the capacity of cxjPI to inactivate trypsin or elastase. Thus the protection of FXIa from inactivation by α1PI and/or the PXIaI did not arise from a) the binding of FXIa to platelets, b) the presence of HMWK, or c) the inactivation of α1PI by platelets. When 125I-labeled FXIa was incubated with α1PI and examined by autoradiography of SDS polyacrylamide gels a complex (Mr 85,000) was observed between the active-site-containing FXIa light chain (Mr 30,000) and α1PI (Mr 54,000). The formation of this complex was inhibited in the presence of activated platelets or platelet releaseates, but was not affected by HMWK. These results support the hypothesis that platelets can regulate FXIa catalyzed F-IX activation by secreting an inhibitor of FXIa that may act primarily outside the platelet microenvironment and by protecting FXIa from inhibition, thereby localizing F-IX activation to the platelet plug.
PURIFICATION AND CHARACTERIZATION OF REACTIVE AND NON-REACTIVE PLASMINOGEN ACTIVATOR INHIBITOR-1 (PAI-1) FROM HUMAN PLACENTA
Authors: Philips M , Juul A G , Thorsen S , Selmer J , Thim L
Published: August 2018

Reactive and non-reactive forms of PAI-1 have been identified in various biological materials. The structural differences between these forms remain to be determined.

A monoclonal antibody specific for a non-reactive PAI-1 and a monoclonal antibody reacting with both the reactive and nonreactive form of the inhibitor were obtained by immunization with a tissue-type plasminogen activator (t-PA)-PAI-1 complex (Philips et al., Thromb Haemostas 1986; 55:213-7). These antibodies were used for the isolation of reactive and non-reactive PAI-1 by solid-phase immunoadsorption from extracts of human placenta. The inhibitor preparations were further purified by HPLC. Reactive and non-reactive PAI-1 both migrated with a Mr ∼ 52,000 when analyzed by SDS-PAGE. Furthermore, the two inhibitor forms were indistinguishable by N-terminal sequence analysis. Two N-terminal sequences were found in about equal ammounts for both the reactive and non-reactive PAI-1. They were Ser-Ala-Val-His-His-Pro-Pro- and a two residues shorter sequence (Val-His-His-Pro-Pro-). These sequences are in agreement with the published cDNA sequence of PAI-1 and shows that the inhibitor is N-terminally heterogeneously processed. The second order rate constant (ki) for the reaction between reactive PAI-1 and single-chain t-PA was about 6 106 M-1s-1. Treatment with 4 M guanidinium-HCl partially converted the non-reactive PAI-1 to a reactive form exhibiting a similar k1 for inhibition of single-chain t-PA. SDS-PAGE showed that the t-PA-PAI-1 complex could be dissociated by 1,5 M NH4OH/ 39 mM SDS resulting in the release of a PAI-1 with approximately the same Mr as native PAI-1. This indicates either that t-PA does not cleave the inhibitor or that it cleaves a peptide bond close to the C-terminus.

In conclusion a non-reactive and a reactive form of PAI-1 can be purified from placenta. The two forms are distinguishable by monoclonal antibodies but they show similar Mr′ls and the same N-terminal sequences.
DETERMINATION OF INTERMEDIATES, PRODUCTS AND CLEAVAGE SITE IN THE REACTION BETWEEN PLASMINOGEN ACTIVATOR INHIBITOR 2 (PAI 2) AND UROKINASES
Authors: Kiso U , Kaudewitz H , Henschen A , Åstedt B , Kruithof E K O , Bachmann F
Published: August 2018

Several specific inhibitors for both urokinase-type and tissue-type plasminogen activators have in recent years been isolated from various organs and cell lines. The inhibitors isolated from human placenta and from the human histiocytic lymphoma cell line U-937 have been shown to be immunologically related.They are denoted as plasminogen activator inhibitor type 2 (PAI 2). It has earlier been demonstrated by gel electrophoresis that during the inhibition reaction at first complexes are formed between activator and inhibitor and then the inhibitor is cleaved and the complex can be dissociated.

In the present study the reactions between urokinase aijd PAI 2 were analysed by means of reversed-phase high-performance liquid chromatography (HPLC) and SDS-polyacrylamide gelelectrophoresis (PAGE). Both high-molecular-weight (54 kDa) and low-molecular weight (33 kDa) urokinase (UK) were used. The PAI 2 was derived from placenta and from U-937 cells. It has a molecular size of L5 kDa. Equimolar amounts of UK and PAI 2 were incubated for 15 min at room temperature. On HPLC and SDS-PAGE analysis new components, corresponding to the UK-PAI 2-complexes, appeared and both UK and PAI 2 disappeared. The apparent sizes of the complexes were approx. 82 kDa and 62 kDa, depending on the type of UK used. The HPLC retention times of the complexes were higher than those of UK or PAI 2. The complexes were stable under the conditions employed for the analyses, but could be completely dissociated by incubation for 1 h at pH 10 and 37°. The released UK behaved identical with the UK starting material. However, the released PAI 2 had decreased in molecular size according to the PAGE analysis, and on HPLC an additional component appeared. As PAI 2 has a blocked N-terminus and the new component shows an N-terminal sequence it must correspond to the C-terminal part of PAI 2. The sequence defines thus the reactive site for the cleavage by the plasminogen activator.
PLASMINOGEN ACTIVATOR INHIBITOR TYPE 1: STUDIES ON STRUCTURE AND REGULATION
Authors: Andreasen P A , Riccio A , Lund L R , Welinder K G , Blasi F , Danø K
Published: August 2018

Human plasminogen activator inhibitor type-1 is an Mr∼54,000 protein which specifically inhibits urokinase-type (u-PA) and tissue-type (t-PA) plasminogen activators. During inhibition, u-PA and t-PA convert PAI-1 to an inactive form with Mr∼50,000. We have determined the amino-terminal amino acid sequence of native and converted PAI-1, and isolated and partly sequenced PAI-1 cDNA. The data show that the conversion of PAI-1 consists of cleavage of an Arg-Met bond 33 residues from the carboxy-terminus, thus localizing the reactive center of the inhibitor to that position, and identifying PAI-1 as an "arg-serpin". PAI-1 activity is known to be influenced by a number of agents; we have studied the mechanisms of the stimulation of PAI-1 activity by transforming growth factor-β (TGF-β) and the synthetic glucocorticoid dexame-thasone in human WI-38 lung fibroblasts and HT-1080 fibrosarcoma cells. Bytheuse of PAI-1 cDNA, TGF-β was found to course a rapid increase in PAI-1 mRNA level in WI-38 cells, reaching a maximal 50-fold enhancement after 8 hours. Dexamethasone caused a 10-fold increase in PAI-1 mRNA in HT-1080 cells, which was detectable after 4 hours and became maximal after 16 hours. In both cases, the 3.4 as well as the 2.4 Kb-PAI-1-mRNA species were increased. Quantitative studies on the effect of these agents on PAI-1 protein levels in cell extracts and culture media by ELISA gave results consistent with the effects on PAI-1 mRNA. These studies suggest that TGF-β and glucocorticoids may exert important controls over plasminogen activation-mediated extracellular proteolysis through an enhancement of PAI-1 gene transcription.
PLASMINOGEN ACTIVATOR INHIBITOR (PAI) ACTIVITY AS WELL AS PAI-1 AND PAI-2 ANTIGEN IN HEALTHY INDIVIDUALS AND HOSPITALIZED PATIENTS
Authors: Kruithof E K O , Nicoloso G , Gudinchet A , Bachmann F
Published: August 2018

The activity of plasminogen activators (PA) is regulated in part by PA-inhibitors. Two distinct PAIs have been identified: PAI-1 and PAI-2. To be able to measure these proteins specifically we have purified PAI-1 and PAI-2, raised antisera and developed specific radioimmunoassays (RIAs), with detection limits in plasma of 10 and 15 ng/ml, respectively.

In a population of over 350 individuals, PAI activity correlated well with PAI-1 :Ag (r=0.699), but not with PAI-2:Ag (r=0.070). In healthy individuals PAI-1 concentrations varied considerably (between 10 and 85 ng/ml, median 29 ng/ml). During venous occlusion (VO) applied in 40 healthy individuals, average PAI-1 in plasma increased fran 27 before, to 43 and 59 ng/ml after 10 and 20 min VO (p <0.001, Wilcoxon test). Overall fibrinolytic activity increased 15 fold, and t-PA:Ag levels eightfold. Increased PAI activity and PAI-1 antigen levels with respect to controls were found in patients with cardiovascular or thromboembolic disease, malignancies, hepatic insufficiency, after major trauma and in the postoperative period. This wide spectrum of pathologies with increased PAI-1 levels supports previous suggestions that PAI-1 behaves as an acute phase reactant. In patients undergoing extracorporeal circulation PAI activity and PAI-1 antigen were measured before and 1 h, 1 d and 7 d after the operation. Highest values of activity and antigen were observed 1 h postoperatively. These values remained elevated the day after the operation, but returned to preoperative levels within 7 days.

PAI-2 antigen concentrations were at or below the detection limit in all controls and the majority of patients. Very high levels of PAI-2 (above 30 ng/ml) were only observed in pregnant women and in patients with hepatocellular carcinoma.

The specific measurement of PAIs thus show increased levels in a variety of clinical conditions. The availability of specific RIAs permits to conduct prospective studies and to evaluate to what degree elevated PAI-1 and PAI-2 concentrations are correlated with the stage of the disease, its prognosis and the risk to develop thromboembolic complications.
THE PLATELET ALLOANTIGEN Zwa (P1A1) IS EXPRESSED BY CULTURED ENDOTHELIAL CELLS
Authors: Giltay J C , Leeksma O C , Borne A E G Kr v d , van Mourik J A
Published: August 2018

Zwa (P1A1) is a platelet specific alloantigen, located on glycoprotein (GP) IIIa, and is of pathogenic importance in alloimmunologic disorders such as neonatal alloimmune thrombocytopenia and post transfusion purpura. As endothelial cells synthesize a plasma membrane protein complex which is structurally closely related to the platelet membrane GP IIb/IIIa complex, we examined whether these cells also express Zwa. Employing a variety of immunochemical techniques, our studies show that endothelial cells indeed can express this antigen at the plasma membrane surface.

We also compared the expression of Zwa on platelets, isolated from umbilical cord blood, with the expression of Zwa on cultured endothelial cells, isolated from the same umbilical cord, of a number of neonates. Both platelets and endothelial cells obtained from the same individual, either expressed Zwa (Zwa positive individuals) or lacked expression of Zwa (Zwa negative individuals). These findings strongly suggest that endothelial-and platelet Zwa are encoded by the same genes.

Thus, Zwa is not exclusively expressed by platelets, also endothelial cells express this alloantigen.

An important consequence could be, that in alloimmunologic disorders in which the Zwa antigen is implicated, not only the platelets, but also the vessel wall is involved.
REGULATION OF CYCLIC NUCLEOTIDE PHOSPHODIESTERASE ACTIVITY IN PLATELETS BY PHOSPHORYLATION
Authors: Grant P G , Mannarino A F , Colman R W
Published: August 2018

Cyclic nucleotide phosphodiesterases (PDE) provide the only known pathway for the hydrolysis of cyclic nucleotides in cells and thus have the potential for modulating the effects of cAMP and cGMP on cells. In platelets a rise in intracellular cAMP levels inhibits platelet aggregation and secretion. Since cAMP exerts many of its effects through a cAMP-dependent kinase we questioned whether phosphorylation of cAMP PDE might be a mode for regulation of PDE activity in platelets. When platelets were incubated for 10 min with forskolin (100 μM) the level of cAMP rose at least 10-fold.

When the low Km cyclic nucleotide PDE was isolated from freeze-thaw lysates of forskolin treated platelets by chromatography on blue dextran-Sepharose, the specific activity of this enzyme was increased 3 to 13-fold over similarly processed control platelets. The specific activity of a second PDE, the cGMP-stimulated cAMP PDE, was increased 1.5 to 3-fold by forskolin treatment of platelets. Forskolin had no direct effect on either purified PDE. The stimulation of the low Km cAMP PDE activity by exposure of platelets to forskolin was blocked when the platelets were simultaneously treated with the protein kinase inhibitor H-8 (100 μM) which is most potent toward cAMP dependent protein kinase indicating that this kinase may be responsible for the stimulation. When platelets which had been prelabeled with 32P inorganic phosphate were treated with forskolin and the low Km cAMP PDE isolated by blue dextran-Sepharose chromatography, a protein migrating in SDS gels at Mr=110,000, the molecular weight of the low Km cAMP PDE, was labeled indicating that phosphorylation of the PDE occurred coincident with stimulation of activity. These results suggest that phosphorylation of the low Km cAMP PDE by protein kinase may be an important regulatory mechanism for cAMP PDE activity and cyclic nucleotide levels in platelets.
THE EFFECTS OF SULFATED POLYSACCHARIDES ON INHIBITION OF THROMBOSIS INDUCED BY DIFFERENT STIMULI
Authors: Van Ryn-McKenna J , Gray E , Weber E , Ofosu F A , Buchanan M R
Published: August 2018

Higher doses of heparin are usually required to achieve a therapeutic effect in patients undergoing elective hip surgery than in patients with idiopathic deep vein thrombosis (DVT). One explanation for this difference is that more heparin is required to prevent thrombosis in hip surgery them recurrent thrombosis in DVT, because the stimulus initiating thrombus formation in each situation is different. This suggests that different procoagulant stimuli may be more or less sensitive to inhibition by heparin. To test this possibility, we measured the effects of heparin (SH), pentosan polysulfate (SP54), and dermatan sulfate (DS) on inhibition of thrombus formation induced by tissue thromboplastin (TTP, 1 mgAg), thrombin (Ha, 1 UAg)/ or Factor Xa (Xa, 20 μt/kg) using a jugular vein/hypercoagulation/stasis ipggel in rabbits. Thrombus size was measured as the amount of 125I-fibrin incorporated into a thrombus formed in jugular veins of rabbits, treated with varying concentrations of SH, SP54 or DS. First, we established the dose of each sulfated polysaccharide (SPS) that was required to inhibit thrombus formation induced by TTP by ∼75%. We then used these doses to assess their ability to inhibit thrombus formation induced by Ha or Xa. SH and SP54 were less effective in inhibiting Ila-induced thrombus formation (<62%), while DS was more effective and inhibited thrombus formation by 95%. In contrast, the doses of SP54 and DS which inhibited TTP-induced thrombosis by ∼75%, inhibited Xa-induced thrombus formation by 60 and 71% respectively, while SH inhibited Xa-induced thrombus formation by 98%. We conclude that sensitivity to inhibition of the 3 different procoagulant stimuli by the various SPS, differs significantly. The choice of SPS as an antithrombotic agent should take into consideration the stimulus initiating thrombosis in each clinical situation.
PLATELET ALTERATIONS IN RESPONSE TO REPETITIVE, SHORT-DURATION LAMINAR SHEAR STRESS
Authors: Joist J H , Bauman J E , Sutera S P
Published: August 2018

We examined platelet aggregation (PAG = loss of single platelets), platelet dense granule release, and platelet injury (LDH loss) in normal human citrated platelet-rich plasma subjected to biologically more relevant repetitive, laminar shear stress of 25 and 50 dyn/cm2 in a computer-controlled cone-plate viscometer. Shear pulse duration (1-3 sec), shear pulse ramp function (rate of shear stress increase and decrease per pulse, 0.6-4 sec), number of shear pulses (1-20) and pauses between shear pulses (0-5 sec) were varied in different combinations to assess the effects of each variable on platelet alterations. Maximum PAG (92±8%) was observed with three 1 sec shear pulses, 0.6 sec ramp function and 1 sec between shear pause. PAG decreased with increasing ramp function, increasing number of shear pulses (>10), and increasing pause duration. Rapid platelet deaggregation (starting at 5 sec) was observed after a single 1 sec shear exposure. The rate of deaggregation decreased with increasing shear pulse number, increasing shear pulse amplitude, and increasing shear pulse duration. In contrast to PAG, dense granule release increased progressively with increasing shear pulse number, duration, and amplitude. No appreciable platelet injury (LDH loss) was observed under the conditions used. The findings indicate that massive reversible PAG can be induced by a single 1 sec shear pulse and that the extent of PAG with more prolonged, repetitive shear exposure is largely a function of platelet deaggregation rather than PAG. Thus, data previously reported from our laboratory and other investigators using prolonged (>5 sec) exposure of platelets to shear stress may require reevaluation.
IDENTIFICATION OF A NEW HUMAN KININ, ILE-SER-BRADYKININ, BY HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY AND SEQUENCE ANALYSIS IN OVARIAN CARCINOMA ASCITES
Authors: Müller E , Henschen A , Wunderer G
Published: August 2018

Human blood has been shown to contain two different kinin precursors, i.e0 the high and the low molecular mass kininogen0 These two kininogens release the same kinins, with the starting sequences Met-Lys-Arg-Pro-, Lys-Arg-Pro- or just Arg-Pro-depending on the releasing enzyme. The kinin starting with Arg-Pro- is denoted as bradykinin. In rats a different kininogen, called T-kininogen, is also present, especially as the major acute-phase protein in this species. The corresponding kinin, T-kinin, has the starting sequence Ile-Ser-Arg-Pro-. This type of kininogen or kinin has previously never been detected in human tissues. However, during the course of the present study evidence for existance of a third human kininogen, giving rise to human T-kinin, was obtained.

Ascites from patients with metastatic ovarian carcinoma has been shown to contain high amounts of vascular permeability-increasing activity as determined by a rat skin-Evans blue test. When the ascites was fractionated by gel filtration followed by reversed-phase high-performance liquid chromatography (HPLC) a component could be isolated which by its total sequence and amino acid composition was identified as Ile-Ser-bradykinin. Several degradation products of this kinin were also detected as separate components in the chromatographies. The human Ile-Ser-bradykinin appeared on reversed-phase HPLC in the same position as synthetic T-kinin. It could be differentiated in this chromatography system from Met-Lys-bradykinin, Lys-bradykinin and bradykinin. It may be assumed that human Ile-Ser-bradykinin is released_ from a third, so far unidentified human kininogen which is only or predominantly expressed under certain pathophysiological conditions, and that therefore this new kinin might be employed as a tumor marker.
KINETIC EFFECTS OF HIGH MOLECULAR WEIGHT KININOGEN AND ZINC ON CONTACT ACTIVATION
Authors: Shore J D , Day D E , Olson S T
Published: August 2018

Previous work in our laboratory showed that Zn2+ enhanced the rate of kallikrein generation by dextran sulfate (DxSO4) in dialyzed normal plasma, but not in Fitzgerald or Hageman prismas. This could be partially explained by a marked effect of Zn2+ on factor XII autoactivation, and our present work involves zinc effects on other reactions of contact activation. At physiological ionic strength (0.15 μ), the kcat/Km for Xlla activation of prekallikrein (PK) was 0.62 μM™1 s™1 which was increased to 4.35 μM™1 s™1 by the presence of 25μg/ml DxSO4. High molecular weight kininogen (HMK) at 40 nM further increased this to 10.8 μM™1 s™1 , and 5 ¼M Zn2+ had no effect. To determine whether these cofactors promote a surface-dependent activation of PK by XIIa under conditions which weaken the protein-surface interactions, the kinetics were examined at 0.3μ. At this ionic strength, kcat/Km was 0.18 μM™1 s™1 and was unchanged by 25μg/ml DxSO4. This was increased to .805 μM™1 s™1 by 150 nM HMK and further increased 10-fold to 8.35 μM™1 s™1 by 10 μM™1 Zn2+ . Qualitative results were obtained at 0.3 μ for the other reciprocal reaction, XII activation by kallikrein (K). To observe XII activation within 2 hours, both 10 μM Zn2+ and 25 μM HMK were essential, indicating that these cofactors have a very large enhancing effect on the kinetics of this reaction. Chromatography of HMWK on DxSO4-agarose ^ljiowed elution of the protein at 0.42 M NaCl in the absence of Zn2+ ,but at 0.88M in its presence, providing evidence that Zn+ markedly increases the affinity of HMK for DxSO4. Our results are consistent with the increased activation rates observed in the presence of Zn2+ and HMK due to enhanced binding affinity of the reacting proteins to surfaces. This is likely to be essential for proper function of the contact system in blood, where many other proteins compete for surface. Supported by USPHS grant HL-25670
ENDOTHELIAL CELLS PRODUCE PLATELET ACTIVATING FACTOR WHICH PRIMES NEUTROPHILS TO RELEASE OXIDANT PRODUCTS
Authors: Wickham N W R , Vercellotti G M , Yin H Q , Jacob H S , Moldow C F
Published: August 2018

Thrombin (THR) is generated during ARDS, sepsis and DIC. We wondered whether it might augment PMN/endothelial cell (EC) interaction and hence amplify EC damage by inducing platelet activating factor (PAF) (JCI 76:2235-2246;1985). To examine further this premise and the mechanisms involved, we measured intracel1ular calcium (Ca1) in human EC (grown on glass cover slips), in a scanning spectrof1uorometer at 37°C after loading with FURA 2 (4μM). Resting Ca1 was 148±22 nM (Mean±SEM) which increased following THR 0.5u/ml to 458±160 nM at 30s, peaking after 1 min at 559±176 nM, and returning to 273±42 nM by 5 min. Phosphatidyl inositol (PI) turnover was assessed in 3H-myoinositol-loaded EC using water-soluble extracts separated by Dowex anion exchange chromatography. Within 30s of THR (lu/ml) stimulation, PI turnover markedly increased, with production of inositol bi- and tri-phosphates showing a >5 fold rise. Associated with these perturbations, THR-treated EC monolayers enhanced O2- generation by FMLP(10™7)-stimulated PMNs (basal levels of 5.73±0.68 O2-/15 min/106 PMN rising to 8.01±0.85 nM (p<0.05)); moreover this enhancement could be completely inhibited with a newly described PAF antagonist BN 52021. PAF production is dependent upon phosphorylation of an acetyl transferase, and Ca1 flux and PI hydrolysis are events known to be associated with protein kinase activation. THR-EC stimulation would seem, therefore, to initiate a sequence of events involving PMN/EC 'cross-talk' leading to contact activation of marginated PMNs by EC-derived PAF. This is an example of a novel paracrine response, and is consistent with our data showing the potent priming effect of PAF on PMN oxidant responses (Blood 68:88A; 1986) and provides evidence for a previously unsuspected pathway that promotes PMN oxidant-mediated EC injury during sepsis or other THR-generating disorders.