bluuebunny/crossref_metadata_2025 huggingface dataset:
Nrf2 negatively regulates STING indicating a link between antiviral sensing and metabolic reprogramming
Authors: Olagnier David , Brandtoft Aske M. , Gunderstofte Camilla , Villadsen Nikolaj L. , Krapp Christian , Thielke Anne L. , Laustsen Anders , Peri Suraj , Hansen Anne Louise , Bonefeld Lene , Thyrsted Jacob , Bruun Victor , Iversen Marie B. , Lin Lin , Artegoitia Virginia M. , Su Chenhe , Yang Long , Lin Rongtuan , Balachandran Siddharth , Luo Yonglun , Nyegaard Mette , Marrero Bernadette , Goldbach-Mansky Raphaela , Motwani Mona , Ryan Dylan G. , Fitzgerald Katherine A. , O’Neill Luke A. , Hollensen Anne K. , Damgaard Christian K. , de Paoli Frank v. , Bertram Hanne C. , Jakobsen Martin R. , Poulsen Thomas B. , Holm Christian K.
Published: August 2018

The transcription factor Nrf2 is a critical regulator of inflammatory responses. If and how Nrf2 also affects cytosolic nucleic acid sensing is currently unknown. Here we identify Nrf2 as an important negative regulator of STING and suggest a link between metabolic reprogramming and antiviral cytosolic DNA sensing in human cells. Here, Nrf2 activation decreases STING expression and responsiveness to STING agonists while increasing susceptibility to infection with DNA viruses. Mechanistically, Nrf2 regulates STING expression by decreasing STING mRNA stability. Repression of STING by Nrf2 occurs in metabolically reprogrammed cells following TLR4/7 engagement, and is inducible by a cell-permeable derivative of the TCA-cycle-derived metabolite itaconate (4-octyl-itaconate, 4-OI). Additionally, engagement of this pathway by 4-OI or the Nrf2 inducer sulforaphane is sufficient to repress STING expression and type I IFN production in cells from patients with STING-dependent interferonopathies. We propose Nrf2 inducers as a future treatment option in STING-dependent inflammatory diseases.
A feed forward loop enforces YAP/TAZ signaling during tumorigenesis
Authors: Gill Mandeep K. , Christova Tania , Zhang Ying Y. , Gregorieff Alex , Zhang Liang , Narimatsu Masahiro , Song Siyuan , Xiong Shawn , Couzens Amber L. , Tong Jiefei , Krieger Jonathan R. , Moran Michael F. , Zlotta Alexandre R. , van der Kwast Theodorus H. , Gingras Anne-Claude , Sicheri Frank , Wrana Jeffrey L. , Attisano Liliana
Published: August 2018

In most solid tumors, the Hippo pathway is inactivated through poorly understood mechanisms that result in the activation of the transcriptional regulators, YAP and TAZ. Here, we identify NUAK2 as a YAP/TAZ activator that directly inhibits LATS-mediated phosphorylation of YAP/TAZ and show that NUAK2 induction by YAP/TAZ and AP-1 is required for robust YAP/TAZ signaling. Pharmacological inhibition or loss of NUAK2 reduces the growth of cultured cancer cells and mammary tumors in mice. Moreover, in human patient samples, we show that NUAK2 expression is elevated in aggressive, high-grade bladder cancer and strongly correlates with a YAP/TAZ gene signature. These findings identify a positive feed forward loop in the Hippo pathway that establishes a key role for NUAK2 in enforcing the tumor-promoting activities of YAP/TAZ. Our results thus introduce a new opportunity for cancer therapeutics by delineating NUAK2 as a potential target for re-engaging the Hippo pathway.
EMT- and stroma-related gene expression and resistance to PD-1 blockade in urothelial cancer
Authors: Wang Li , Saci Abdel , Szabo Peter M. , Chasalow Scott D. , Castillo-Martin Mireia , Domingo-Domenech Josep , Siefker-Radtke Arlene , Sharma Padmanee , Sfakianos John P. , Gong Yixuan , Dominguez-Andres Ana , Oh William K. , Mulholland David , Azrilevich Alex , Hu Liangyuan , Cordon-Cardo Carlos , Salmon Hélène , Bhardwaj Nina , Zhu Jun , Galsky Matthew D.
Published: August 2018

Cancers infiltrated with T-cells are associated with a higher likelihood of response to PD-1/PD-L1 blockade. Counterintuitively, a correlation between epithelial–mesenchymal transition (EMT)-related gene expression and T-cell infiltration has been observed across tumor types. Here we demonstrate, using The Cancer Genome Atlas (TCGA) urothelial cancer dataset, that although a gene expression-based measure of infiltrating T-cell abundance and EMT-related gene expression are positively correlated, these signatures convey disparate prognostic information. We further demonstrate that non-hematopoietic stromal cells are a major source of EMT-related gene expression in bulk urothelial cancer transcriptomes. Finally, using a cohort of patients with metastatic urothelial cancer treated with a PD-1 inhibitor, nivolumab, we demonstrate that in patients with T-cell infiltrated tumors, higher EMT/stroma-related gene expression is associated with lower response rates and shorter progression-free and overall survival. Together, our findings suggest a stroma-mediated source of immune resistance in urothelial cancer and provide rationale for co-targeting PD-1 and stromal elements.
Author Correction: Chemical nature of alkaline polyphosphate boundary film at heated rubbing surfaces
Authors: Wan Shanhong , Tieu A. Kiet , Zhu Qiang , Zhu Hongtao , Cui Shaogang , Mitchell David R. G. , Kong Charlie , Cowie Bruce , Denman John A. , Liu Rong
Published: August 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
A novel logistic regression model combining semi-supervised learning and active learning for disease classification
Authors: Chai Hua , Liang Yong , Wang Sai , Shen Hai-wei
Published: August 2018

Traditional supervised learning classifier needs a lot of labeled samples to achieve good performance, however in many biological datasets there is only a small size of labeled samples and the remaining samples are unlabeled. Labeling these unlabeled samples manually is difficult or expensive. Technologies such as active learning and semi-supervised learning have been proposed to utilize the unlabeled samples for improving the model performance. However in active learning the model suffers from being short-sighted or biased and some manual workload is still needed. The semi-supervised learning methods are easy to be affected by the noisy samples. In this paper we propose a novel logistic regression model based on complementarity of active learning and semi-supervised learning, for utilizing the unlabeled samples with least cost to improve the disease classification accuracy. In addition to that, an update pseudo-labeled samples mechanism is designed to reduce the false pseudo-labeled samples. The experiment results show that this new model can achieve better performances compared the widely used semi-supervised learning and active learning methods in disease classification and gene selection.
Optimizing the light delivery of linear-array-based photoacoustic systems by double acoustic reflectors
Authors: Wang Yuehang , Lim Rachel Su Ann , Zhang Huijuan , Nyayapathi Nikhila , Oh Kwang W. , Xia Jun
Published: August 2018

Although linear transducer arrays have been intensely used in photoacoustic imaging, their geometrical shape constrains light illumination. Today, most linear array based photoacoustic systems utilize side-illumination geometry, which consists of two line fiber bundles attached to the side of the probe. The angled light illumination increases the light travel distance in deep tissue, consequently limiting the imaging depth. This issue was partially addressed by adding a right angle prism in front of the transducer. While this design makes the light illumination and acoustic detection co-axial, the transducer and the fiber bundles are orthogonal to each other, making the system inconvenient for handheld use. To overcome this limitation, here we propose a double-reflector design, in which the second reflector redirects the acoustic signals by another 90°, so that the transducer and the fiber bundle are now parallel to each other. In this design, both the transducer and fiber bundle output are fitted into a compact housing for convenient handheld imaging. To evaluate the efficiency of our design, we performed various phantom and humanin vivoexperiments. Our results demonstrate that the double-reflector design indeed provides deeper imaging depth and it also allows for easy imaging of objects with uneven surfaces.
Google searches do not correlate with melanoma incidence in majority English speaking countries
Authors: McDonald Laura , Simpson Alex , Graham Sophie , Schultze Anna , Nordstrom Beth , Durani Piyush , Mehmud Faisal , Ramagopalan Sreeram V.
Published: August 2018

Recent reports have suggested that internet search behaviour may be a valuable tool to estimate melanoma incidence and mortality. Previous studies have used incorrect statistical methods, were focussed on the United States and/or did not use non-cancer control search terms to provide a context for interpreting the effects seen with the cancer-related terms. Using more robust statistical methods we found that no cancer search terms were significantly, or strongly correlated with melanoma incidence in 6 countries.
Shape-controlled synthesis of nanostructured Co-doped ZnO thin films and their magnetic properties
Authors: Taher F. A. , Abdeltwab E.
Published: August 2018

Three ferromagnetic complex nanostructures (flower, sheaf, and cactus) of Co-doped ZnO thin films were selectively grown from 1D to 3D.
Isolation, purification and the anti-hypertensive effect of a novel angiotensin I-converting enzyme (ACE) inhibitory peptide from Ruditapes philippinarum fermented with Bacillus natto
Authors: Chen Yingyun , Gao Xiang , Wei Yuxi , Liu Qi , Jiang Yuhong , Zhao Ling , Ulaah Sadeeq
Published: August 2018

A novel ACE inhibitory peptide (Val-Ile-Ser-Asp-Glu-Asp-Gly-Val-Thr-His) with a high anti-hypertensive effect isolated from Ruditapes philippinarum fermented with Bacillus natto.
The architectures of iterative type I PKS and FAS
Authors: Herbst Dominik A. , Townsend Craig A. , Maier Timm
Published: August 2018

The architectures of fatty acid synthases and iterative polyketide synthases are remarkably divergent despite their related biosynthetic logics.
Rare-earth-doped fluoride nanoparticles with engineered long luminescence lifetime for time-gated in vivo optical imaging in the second biological window
Authors: Tan Meiling , del Rosal Blanca , Zhang Yuqi , Martín Rodríguez Emma , Hu Jie , Zhou Zhigang , Fan Rongwei , Ortgies Dirk H. , Fernández Nuria , Chaves-Coira Irene , Núñez Ángel , Jaque Daniel , Chen Guanying
Published: August 2018

We report on rare-earth-doped fluoride nanoparticles with a long lifetime and intense infrared emission in the second biological window for in vivo luminescence lifetime imaging.
How the crystal structure and phase segregation of Au–Fe alloy nanoparticles are ruled by the molar fraction and size
Authors: Tymoczko Anna , Kamp Marius , Prymak Oleg , Rehbock Christoph , Jakobi Jurij , Schürmann Ulrich , Kienle Lorenz , Barcikowski Stephan
Published: August 2018

An ultrastructure of Au–Fe alloy nanoparticles is predefined by the Au : Fe target composition under certain size restrictions as predicted by theoretical modeling.
Nickel catalyzed site selective C–H functionalization of α-aryl-thioamides
Authors: Bandyopadhyay Debashruti , Thirupathi Annaram , Dhage Nagsen Munjaji , Mohanta Nirmala , Peruncheralathan S.
Published: August 2018

A nickel catalyzed C–H bond functionalization reaction has been used for the first time to study an intramolecular site-selective C–S bond formation of arenes.
Attenuation of guanine oxidation via DNA-mediated electron transfer in a crowded environment using small cosolutes
Authors: Tanaka Makiko , Matsumoto Takayuki , Iida Hiroki
Published: August 2018

Guanine oxidation induced by photoirradiation on a pyrene-modified oligonucleotide was investigated under molecular crowding using small cosolutes such as glycerol.
Design and controllable synthesis of ethylenediamine-grafted ion imprinted magnetic polymers for highly selective adsorption to perchlorate
Authors: Shen Haoyu , Sun Meina , Hu Meiqin , Cheng Jinjin
Published: August 2018

A series of ethylenediamine-grafted ion imprinted magnetic polymers (Fe3O4@IIPs) were synthesized via ultrasonic assisted suspension polymerization with perchlorate (ClO4−) as an ion imprinting template.
Gesture‐based registration correction using a mobile augmented reality image‐guided neurosurgery system
Authors: Léger Étienne , Reyes Jonatan , Drouin Simon , Collins D. Louis , Popa Tiberiu , Kersten‐Oertel Marta
Published: August 2018

In image‐guided neurosurgery, a registration between the patient and their pre‐operative images and the tracking of surgical tools enables GPS‐like guidance to the surgeon. However, factors such as brainshift, image distortion, and registration error cause the patient‐to‐image alignment accuracy to degrade throughout the surgical procedure no longer providing accurate guidance. The authors present a gesture‐based method for manual registration correction to extend the usage of augmented reality (AR) neuronavigation systems. The authors’ method, which makes use of the touchscreen capabilities of a tablet on which the AR navigation view is presented, enables surgeons to compensate for the effects of brainshift, misregistration, or tracking errors. They tested their system in a laboratory user study with ten subjects and found that they were able to achieve a median registration RMS error of 3.51 mm on landmarks around the craniotomy of interest. This is comparable to the level of accuracy attainable with previously proposed methods and currently available commercial systems while being simpler and quicker to use. The method could enable surgeons to quickly and easily compensate for most of the observed shift. Further advantages of their method include its ease of use, its small impact on the surgical workflow and its small‐time requirement.
Virtual interaction and visualisation of 3D medical imaging data with VTK and Unity
Authors: Wheeler Gavin , Deng Shujie , Toussaint Nicolas , Pushparajah Kuberan , Schnabel Julia A. , Simpson John M. , Gomez Alberto
Published: August 2018

The authors present a method to interconnect the Visualisation Toolkit (VTK) and Unity. This integration enables them to exploit the visualisation capabilities of VTK with Unity's widespread support of virtual, augmented, and mixed reality displays, and interaction and manipulation devices, for the development of medical image applications for virtual environments. The proposed method utilises OpenGL context sharing between Unity and VTK to render VTK objects into the Unity scene via a Unity native plugin. The proposed method is demonstrated in a simple Unity application that performs VTK volume rendering to display thoracic computed tomography and cardiac magnetic resonance images. Quantitative measurements of the achieved frame rates show that this approach provides over 90 fps using standard hardware, which is suitable for current augmented reality/virtual reality display devices.
Immer up to date
Authors: Stark Uwe
Published: August 2018

Immer auf dem neusten Informationsstand zu sein, ist für OP-Personal sehr wichtig, da häufig neue Systeme, Techniken oder Geräte zum Einsatz kommen. Doch wie
kann sichergestellt werden, dass tatsächlich alle Mitarbeiter die Infos erhalten? Unser Autor klärt auf.
Morbiditätsorientierter Risikoausgleich in der Schweiz: Wie Kassen sich auf die Einführung vorbereiten – Einige Überlegungen aus
gesundheitsökonomischer Sicht
Authors: Oggier Willy
Published: August 2018

Im Rahmen der sozialen Krankenversicherung in der Schweiz steht der Wechsel auf einen morbiditätsorientierten Risikostrukturausgleich bevor. Mittels einer
Befragung diverser Geschäftsleitungs-Mitglieder von Krankenversicherern wurde der Frage nachgegangen, wie sich diese darauf vorbereiten. Dabei zeigten sich
Unterschiede im Bereich der (Weiter-) Entwicklung integrierter Versorgungsmodelle, um vermehrt chronisch Kranke statt gesunde Versicherte anzulocken.
Stereoretentive Suzuki–Miyaura and Kumada–Tamao–Corriu Cross-Couplings for Preparing (E)- and (Z)-Stereodefined, Fully Substituted α,β-Unsaturated Esters: Application for a Pharmacophore Synthesis
Authors: Tanabe Yoo , Sato Yuka , Ashida Yuichiro , Yoshitake Daisuke , Hoshino Mayuko , Takemoto Taichi
Published: August 2018

Substrate-general stereocomplementary Suzuki–Miyaura (SM) cross-coupling and relevant Kumada–Tamao–Corriu (KTC) cross-coupling reactions for preparing (E)- and (Z)-stereodefined, fully substituted α,β-unsaturated esters are described. The SM cross-coupling reactions were performed under Pd(OAc)2/SPhos/iPr2NEt catalysis (24 examples, 66–99% yield). The KTC cross-coupling reactions were also performed under similar Pd(OAc)2/SPhos conditions (11 examples, 50–98% yield). Application to a useful pharmacophore containing a cyclopropane structure was investigated, wherein distinctive (E)- and (Z)-stereochemical difference between XPhos and SPhos was observed. A plausible mechanism for the stereoretention and stereoinversion cross-coupling reactions is proposed.
Factor-XII Congenital Deficiency. A New Family Study
Authors: Lucia J F , Ercoreca L , Torres M , Giralt M , Raichs A
Published: August 2018

This report describes two people in a family with Hageman trait (homozygotes) (Factor XII = 0.06%). In addition eight family members were studied to evaluate the inheritance of this congenital deficiency. A study of the Kallikrein-Kininogen system induced by the fragments of Factor XII was also carried out.

It is concluded that the inheritance is as described by Veltkamp and that the Kallikrein release from the prekallikreinogen (Fletcher factor) “in vitro” is related to the amount of Factor XII procoagulant protein.
Studies on the Thrombogenic Activities in Two Prothrombin Complex Concentrates
Authors: Hedner Ulla , Nilsson Inga Marie , Bergentz Sven-Erik
Published: August 2018

The effect on the coagulation and fibrinolytic systems of various factor IX concentrates after addition of heparin, antithrombin III or Trasylol to the concentrate before infusion into dogs was studied in an attempt to characterize the clot-promoting activity or activities in these concentrates. After infusion of Preconativ (AB Kabi; 100 u factor IX/kg bodyweight) only small decreases of fibrinogen and platelet count in the samples taken 1 and 4 hrs after infusion were found. Addition of heparin (10 u/ml; 5 dogs) or Trasylol (40 u/u factor IX initially followed by 10,000 u/h; 3 dogs) had no effect but addition of antithrombin III (100 u/kg; 3 dogs) prevented all changes. Infusion of Konyne (Cutter Laboratories; 100 u/kg bodyweight) induced marked decreases of both fibrinogen and the platelet count at 1, 4 and 24 hrs after infusion and the ethanol gelation test became positive. Addition of heparin (10 u/ml; 5 dogs) diminished the changes but did not completely counteract them. Antithrombin III (100 u/kg; 3 dogs) added to the concentrate before infusion also reduced the induced changes to about the same extent as heparin. Trasylol (40 u/u factor IX initially followed by 10,000 u/h; 3 dogs) did not seem to have any effect. Addition of both antithrombin III and Trasylol (4 dogs) did, however, prevent almost all changes.

It is thus obvious that the two commercial factor IX concentrates used may contain clot promoting activities and that these activities may differ between various concentrates.
Plasma High Molecular Weight Kininogen Concentration in Health and in Chosen Impairments of Haemostasis. Evidence that Plasmin Uncovers a New Antigenic Site in High Molecular Weight Kininogen
Authors: Kleniewski Józef
Published: August 2018

High molecular weight kininogen (HMW-kininogen) concentration was measured in the plasma of healthy blood donors, patients with haemophilia A, idiopathic thrombocytopoenic purpura, deep vein thrombosis treated with oral anticoagulants and patients treated with streptokinase (SK). The concentration of HMW-kininogen in the plasma of healthy subjects was 92 ± 15 μg/ml. The values obtained in patients’ plasma were not different statistically. In the plasma of patients treated with repeated infusion of SK, a significant increase of HMW-kininogen antigen activity was noted after each injection of the drug. Similar results were obtained when SK was added to plasma “in vitro” or when a purified preparation of HMW-kininogen was treated with plasmin. These and additional data obtained suggest that plasmin uncovers in the HMW-kininogen molecule a new antigenic site(s) common to HMW-kininogen and low molecular weight kininogen and new antigenic site(s) specific only for HMW-kininogen.
Inhibition by N-Acetyl Neuraminic (Sialic) Acid of Platelet Aggregation Induced by Different Stimuli
Authors: Kovács Iren B , Görög P
Published: August 2018

Addition of N-acetyl neuraminic acid (sialic acid, NANA) to citrated rat platelet-rich plasma significantly inhibited aggregation induced by near-threshold concentration of ADP, collagen or thrombin. In heparinized rat platelet-rich plasma aggregation of platelets induced by endotoxin or tumour cells of various origins was also inhibited by sialic acid.

It is suggested that exogenous or endogenous sialic acid may act against various aggregating stimuli on the platelet membrane by masking a common factor through which various aggregating agents exert their effect.
Changes in Platelet Aggregability after Ovariectomy
Authors: Yamazaki Hiroh , Motomiya Takeshi , Sonoda Minoru , Miyagawa Noboru
Published: August 2018

Changes in platelets in 48 patients with uterine myoma before and after hysterectomy with and without ovariectomy were examined. Bilateral ovariectomy in 25 cases (ovariec-tomized group) and unilateral or non-ovariectomy in 23 cases (control group) were performed at the hysterectomy. Platelet count and an appearance rate of secondary aggregation decreased at one day after and increased at one week after the operation, similarly in both the ovariectomized and the control group. The appearance rate of secondary aggregation was reflected in an intensity of aggregation at 5 min after the addition of reagent to PRP. At one month after the operation, the appearance rate of secondary aggregation induced by 3 μM ADP showed a statistically significant decrease in comparison with the preoperation value (P <0.05) and the enhancement of 5-min aggregation was still observed in the control group, while ceased in the ovariectomized group. The difference between the two groups was significant (P < 0.05). There was almost no change in the speed and intensity of primary and secondary aggregation during the observation period. No significant differences in collagen-induced aggregation were noted between the two groups. The results suggest that ovarian hormones, mainly estrogen, facilitate platelet activation which is mediated by the so-called secondary aggregation.
“Dirty” Fiber - “Clean” Fiber: A Theory of the Organization of Fibrin from Fibrinogen
Authors: Branson Herman E
Published: August 2018

A theory of fibrin formation is proposed in which gel fiber fabrication is coordinated by two distinct sets of complexing filaments emanating from spherical fibrinogen-derived structural subunits. The formulation is an attempt to correlate the previously reported ultramicroscopic negative-contrast images of fibrinogen and fibrin with a similar but unique spheroidal body observed during the organization of dysfibrin Seattle. This slow clotting dysfibrinogen manifested a predisposition to form aperiodic fibers when thrombic proteolysis and polymerization were curtailed by the progressively earlier application of an acid stain embedment reagent (uranyl acetate). The unstriated fibers were unevenly surrounded by the electron dense stain and manifested a “dirty” appearance. This “primordial” fiber was comprised of linear chains of (10 nm) complexed spheres with (15 nm) lateral filamentous projections. Fibrinogen Seattle consistently generated typically striated (26 nm), “clean”, or “mature” fiber gels when polymerization was allowed to proceed. The proposed role of these lateral filaments is to engage, align, and stabilize similar processes on globular subunits in adjacent linear chains of the “primordial” fiber. The behavior of the negative contrast reagent during the fibrinogen to fibrin conversion is assessed as a reflection of the distribution and orientation of polar residues. The“clean” or striated fiber is depicted as a highly fenestrated hollow cylinder with a hydrophilic interior. The model is fitted to ultrastructural studies on the progression of transamidation of fibrin by factor XIIIa.
A Simple Rapid Method for Isolating Soluble Fibrin Complexes from Fibrinogen by Treatment with Thrombin and t-AMCHA
Authors: Hayashi Shigeru , Yamada Kaneo
Published: August 2018

Using treatment with thrombin associated with trans-aminomethylcyclohexane carboxylic acid (t-AMCHA), a simple and rapid method for isolating soluble fibrin complexes (SFC) from fibrinogen in the plasma was developed. By this procedure, the recovery rates of SFC and early FDP (mainly X) increased according to the concentration of t-AMCHA, reaching a maximum at 286 mM t-AMCHA. On the other hand, the recovery rate of fibrinogen remained below 1.5% and that of late FDP was almost 100% at all concentrations of t- AMCHA. These results suggested that SFC and FDP could be isolated from fibrinogen by thrombin and t-AMCHA (286 mM) treatment. Moreover, it was possible to isolate SFC from FDP using gel filtration after treatment with thrombin and t-AMCHA. The SFC could be quantified by assay of the eluted fractions containing SFC by the staphylococcal clumping test.
Localization of Tissue Fibrinolysis in the Gastrointestinal Tract
Authors: Stenberg Björn , Risberg Bo , Bois Marc , Zettergren Lennart , Peterson Hans-Inge
Published: August 2018

Tissue fibrinolysis in the stomach and intestine of the rat was studied with a histochemical technique. After perfusion of blood vessels to reduce the influence of circulating plasminogen activator and inhibitor fibrinolysis was localized mainly to submucosal arteries and to the serosa of the gastrointestinal tract. This is opposite to previous observations, in which tissue fibrinolysis in the gastrointestinal tract was suggested to be mainly localized to veins. A method for semiquantitative analysis of tissue fibrinolysis in the rat stomach is described.
Tranexamic Acid and Gastric Fibrinolysis in the Rat
Authors: Stenberg Björn , Risberg Bo , Peterson Hans-Inge
Published: August 2018

An optimal inhibition of tissue fibrinolysis, studied by a histochemical fibrin slide technique in the rat stomach, was obtained by administration of tranexamic acid in a dose of 60 mg/100 g body weight. A significant fibrinolysis inhibition was found within 5 min, when tranexamic acid in this dose was given either intravenously or intragastrically. A prolonged duration of fibrinolysis inhibition was observed after intragastric administration. After 4 hr no inhibitory effect of tranexamic acid could be recorded, irrespective of the route of administration.
Changes in Platelet Functions, Coagulation and Fibrinolysis in Uncomplicated Cases of Acute Myocardial Infarction
Authors: Knudsen J Bjerre , Gormsen J , Skagen K , Amtorp O
Published: August 2018

Platelet aggregation and serotonin-release in vitro and some coagulation and fibrinolysis parameters were studied closely in 12 patients with non-complicated acute transmural myocardial infarction from the very beginning, for 3 weeks.

The aggregability with ADP, epinephrine and collagen and the serotonin-release was significantly reduced the first days. Significantly increased aggregability and serotoninrelease developed after a week, with peak activity on days 14-16. Most patients still exhibited increased activity at the discharge on days 21-22.

Positive ethanol gelation tests developed after day 1 in most patients with a peak at day 5, contemporary with peak activities of factor VIII and negatively correlated to factor XIII activity, quantitated biologically. These values were normalized on discharge. Antithrombin III (Xa) remained unchanged, normal to slightly elevated.

The fibrinolytic activity decreased after day 1 with lowest activity on day 5, contemporary with peak activity of antiplasmin. Around 50% of the patients showed decreased activity on discharge.
Acquired von Willebrand’s Syndrome during Autoimmune Disorder
Authors: Pizzuto Javier , Ambriz Raul , de la Paz Reyna Maria , Monrroy Luis M , Morales Manuel R , Aviles Agustin , Conte Guillermo , Enriquez Ruben
Published: August 2018

A case with evidence of acquired von Willebrand’s syndrome associated with systemic lupus erythmatosus and Sjögren’s syndrome is described. The patient, who had no family history of bleeding, presented a haemorrhagic diathesis of recent origin, the bleeding time was prolonged, procoagulant Factor-VIII and von Willebrand factor levels were low and platelet aggregation was decreased with different concentrations of Ristocetin®.

No improvement was seen after the tranfusion of cryoprecipitates, and there was no increase in procoagulant Factor-VIII.

Clinical improvement resulted after treatment with corticosteroids, and later, the laboratory abnormalities characteristic of von Willebrand’s disease became normal. The level of procoagulant factor-VIII reached the very high level of 810%.
The Turnover in Normal Dogs of Prothrombin and Its Fragments; Effect of Induced Intravascular Coagulation
Authors: Owen Charles A , Mann Kenneth G , McDuffie Frederic C
Published: August 2018

When 125I-labeled canine prothrombin was given to normal adult dogs intravenously, it was calculated that 240% of the plasma prothrombin crossed the capillary barrier per day, 410% of the interstitial prothrombin returned to the blood stream daily, and 79% of the plasmatic prothrombin was catabolized per day. These data are in close agreement with those observed for bovine prothrombin in calves by Takeda (1970).

When derived from normal dog prothrombin, prethrombin-1 is a mixture of 2 polypeptides, one larger than the other, and both present in about equal amounts. The longer peptide, “prethrombin-1-long,” was catabolized twice as fast as prothrombin, and the shorter, “prethrombin-1-short,” 4 times faster. Prothrombin fragment-1 was catabolized by the normal dog still more rapidly.

The catabolism of prothrombin was not accelerated in 3 dogs receiving continuous infusions of a thromboplastic emulsion of dog brain. Nor was the level of prothrombin in their plasma remarkably altered.
The Plasminogen Content of Commercial Preparations and of Normal Donor Plasma in Relation to the Plasmin Content ot the 1st International Plasmin Reference Preparation
Authors: Wolf Peter
Published: August 2018

Kabi human plasminogen and plasmin and two Behringwerke preparations of human plasminogen were examined for antigen content, purity and specific activity with the 1st International W.H.O. human plasmin reference preparation and with the plasminogen content of an 8 donor normal plasma pool. In relation to the plasminogen content of the preparation with the highest specific activity, the 8 donor plasma pool contained 0.186 mg/ ml of plasminogen. This plasminogen on complete conversion to plasmin by streptokinase or urokinase corresponded to 4.35 International units/ml of plasmin as defined by the International reference preparation.

Protein adsorption from highly purified plasminogens of low protein content induced variable underestimates of antigen and of biological activity. To prevent this it is recommended to issue these purified preparations in an inert carrier medium or alternatively to release these preparations with data pertaining to salt content and optical measurement prior to lyophilisation. When standards of high purity and low protein content are being examined for antigen and enzyme, it is recommended likewise that an inert protein carrier should be present in the diluent. Measurement of proactivator was considered to be unsuitable in reference to proactivator content of highly purified plasmin and plasminogen.
Potentiating Effect of Adrenaline on Adenosine Diphosphate - Induced Reduction in Rabbit Circulating Platelet Count: Inhibition by Dihydroergotoxine
Authors: Holmes Ian B
Published: August 2018

The number of circulating platelets was monitored in anaesthetized rabbits by a contiuous flow technique, using a Technicon Autocounter®. Transient reductions in circulating platelet count induced by a submaximal dose of adenosine diphosphate (ADP) were potentiated by concomitant infusion of adrenaline at doses (1-25 μg/kg i.v.) which did not influence platelet count when infused alone. The adrenaline effect was dose-dependent. Repeated infusions of adrenaline at 15 min intervals resulted in reproducible reductions in circulating platelet count during an observation period of at least 105 min.

Dihydroergotoxine (DHET), administered either i.v. (2.5 - 10 μg/kg) or intraduodenally (i.d.; 25 - 100 μg/kg), inhibited adrenaline-induced potentiation dose-dependently; ADP- induced effects were not influenced. Duration of action was relatively long, and significant inhibitory activity was still apparent 50 (i.v.) and 115 (i.d.) min after drug administration.

DHET doses inhibiting adrenaline-induced potentiation of platelet aggregation in the rabbit are similar to doses used in the treatment of impaired human cerebral function. It is conceivable that DHET could prevent activitation of human platelets by catecholamines released into the blood stream in clinical stress situations.
Differential Contribution of Oxidative and Glycolytic Energy to Thrombin-Induced Platelet Functions
Authors: Kobayashi Bonro , Watanabe Yasuko , Takasugi Naoyuki , Kurita Makiko
Published: August 2018

When washed rabbit-blood platelets were preincubated in an artificial medium in the absence of external substrates, they aggregated in response to a low concentration of thrombin. The aggregation was completely inhibited after the preincubation with respiratory inhibitors. When glucose together with the respiratory inhibitors was added during the incubation, the aggregation was accelerated, whilst it was counteracted when Krebs-cycle substrates were added.

ATP was generated actively during the incubation in the absence of external substrates, as well as in the presence of succinate. The ATP-generation was extremely inhibited by oligomycin. When glucose was added during the incubation with the respiratory inhibitor, the comparable amount of ATP with those in the oxidative systems was generated. Metabolic ADP was accumulated in the oxidative systems, particularly in the presence of succinate, in contrast to its low level in the glucose + oligomycin system. The results suggest that the counteraction of the aggregation by the Krebs-cycle substrate is attributed to the low adenylate energy charge. It is suggested that anaerobic glycolysis creates favorable energy condition for aggregation as compared with oxidative phosphorylation, although the washed platelets can be energized to a level above threshold of the aggregation when either one of the two energy generating systems is exerted.

After the incubation of the platelets in the presence of thrombin, a higher level of metabolic ATP was observed under glycolytic condition, than under oxidative condition. Pulse-labelling experiments showed that ADP produced during the aggregation was rephosphorylated in a later part of the incubation in the glucose + KCN-fortified system. In the succinate-fortified system, the re-phosphorylation was very slow. The results suggest that oxidative phosphorylation is reduced in platelet aggregates treated with thrombin.
Platelet Adhesiveness to Glass
Authors: Page R L , Mitchell J R A
Published: August 2018

1. When anticoagulated blood is placed in a rotating glass flask, the blood/air interface initiates platelet aggregation, and the aggregates are trapped on the flask wall, without adhering to it, by the thin film of blood which forms during rotation. The interface; allows CO2 loss so that the pH of the rotating blood rises markedly and this rise is associated with the release of 3H-5HT from platelet. When CO2 diffusion and consequent pH rise is prevented, platelet loss and 3H-HT release are significantly reduced.

2. A simple method for assessing the adhesiveness of single platelets to glass using a Neubauer haemocytometer chamber has been developed. The results obtained are independent of platelet number which allows the test to be used in conditions in which abnormal platelet behaviour is associated with a low platelet-count.

3. Adhesiveness was negligible in heparinised PRP, and was greater in EDTA PRP than in citrated PRP. Heparin abolished the increased adhesiveness observed with the other anticoagulants and adhesiveness did not seem to be directly related to residual plasma calcium concentrations. Platelets adhered more readily to siliconised glass surfaces than to untreated glass, and adhesion was markedly temperature-dependent, being maximal at 4°C in heparinised PRP, and at 20° C in EDTA PRP.

4. Adhesiveness was enhanced by aggregating agents, this enhancement being prevented by inhibitors of aggregation such as the dipyridamole analogue VK 774. Adhesiveness was unaffected by acetyl-salicylic acid.

5. Adhesiveness increased markedly after surgical operations and myocardial infarction. Within-person variation was considerable, and the test is of no value in individual patients.
Coagulation in the Sand Crab (Ovalipes Bipustulatus)
Authors: Madaras F , Parkin J D , Castaldi P A
Published: August 2018

The coagulation mechanism of the sand crab (O. bipnsulatus) has been investigated. From the coagulocytes (amoebocytes) present in the crab haemolymph (blood), fibrinogen (coagulogen) was isolated. It was shown to be homogeneous by electrophoresis on S.D.S. polyacrylamide gel and had a molecular weight similar to the A α-chain of human fibrinogen. Unlike human fibrinogen it cannot be dissociated by reduction. In fibrin polymerization, a crosslinking process takes place and this process was inhibited by glycine ethyl ester. A fibrin stabilizing factor is present in the crab haemolymph and this protein was able to cross-link human fibrin in the same manner as human factor XIII.
Inactivation of Factor VIII by a Mechanism Independent of the Generation of Thrombin
Authors: Triantaphyllopoulos D C
Published: August 2018

Thrombin first activates and then inactivates factor VIII and for this reason thrombin has been considered responsible for the inactivation of factor VIII which occurs during clotting. Experiments described in this paper indicated that the activity of factor VIII is not reduced in factor IX or factor X deficient sera, while on the other hand this factor becomes inactivated in blood anticoagulated with high concentrations of hirudin which inhibit thrombin activity completely. This suggests that some other factor, besides thrombin, which is generated only in trace amounts in factor IX or factor X deficient plasmas, is also able to inactivate factor VIII. Purified factor X activated with insolubilized trypsin was added to purified preparations of factor VIII, which were free of both fibrinogen and prothrombin. Factor Xa was allowed to act for 5-60 minutes and then inactivated with phenylmethanesul- fonyl fluoride. Depending on the duration of the action of factor X a partial or complete inactivation of factor VIII was observed. This inactivation was also observed in the presence of hirudin, thus excluding the possibility that the effect was due to contamination with trace amounts of thrombin.
Studies on Metabolism of Urokinase and Mechanism of Thrombolysis by Urokinase
Authors: Ueno Tatsuo , Kobayashi Norio , Maekawa Tadashi
Published: August 2018

Pharmacokinetics of intravenously injected 125I-labeled urokinase (125I-UK) of a molecular weight of 33,000 daltons in normal rabbits and patients with various diseases were investigated. The plasma clearance of 125I-UK in rabbits was described by a biexponential curve within six hours with a half-life of 8 minutes, 2.3 hours, respectively. The radioactivity in the liver and kidneys 15 minutes after iv injection with 125I-UK was 9.6% and 14.0% of the radioactivity injected, respectively. Approximately 80% of the total radioactive material injected was excreted in the urine in 18 hours. No increase in activator activity in the urine was observed after a large amount of UK injection. Activity uptake of 125I-UK by experimentally induced arterial thrombus was little. Lysis of the stasis thrombus was produced by injecting 7.5 × 104 IU of UK in only one out of 8 rabbits. In vitro contact experiment revealed that transfer of 125I-UK to plasma clot is slow (24 hours for 10% of 125I-UK by plasma clot). In 4 patients plasma clearance of 125I-UK was essentially similar to that in rabbits. From the results obtained optimal dosage regimen of UK administration for complete thrombolysis in vivo was discussed.
Plasminogen Activator (Urokinase) from Cultured Cells
Authors: Lewis L James
Published: August 2018

Secretion of large quantities of urokinase by cultured renal cells suggested tissue culture as a means of production to meet demand for the material and to obtain guidelines for optimization of production. Rates of secretion and overall yields of urokinase from confluent cultures of renal cells have been studied in relation to species differences, effects of passage of cells, inoculum density, and volume of maintenance media. Aided in part by an advantage gained through addition of glycine to maintenance media, it is now possible to harvest urokinase at concentrations of the order of 800 CTA units per ml. Such concentrations are of the order of 102 times that occurring in human male urine.
Influence of Coagulation on the Activation of Plasminogen by Streptokinase and Urokinase
Authors: Takada Akikazu , Urano Tetsumei , Takada Yumiko
Published: August 2018

Human plasma was mixed with Ca++ or thrombin, and urokinase (UK) or streptokinase (SK) and a chromogenic substrate (S-2251: H-D-Val-Leu-Lys-pNA) specific to plasmin. The hydrolysis of S-2251 was higher when clot was formed by the addition of Ca++ or thrombin than in the absence of clot. The hydrolysis of S-2251 by euglobulin in the presence of UK was also higher when clot was formed, thus, inhibitors may not be related to the better activation of plasminogen, in the presence of fibrin clot. It may be suggested that plasminogen was better activated by activators (UK and SK) in the clot than in its absence.
Turning psychology into policy: a case of square pegs and round holes?
Authors: Walker Carl , Speed Ewen , Taggart Danny
Published: August 2018

This paper problematizes the ways in which the policy process is conceived in published psychological research. It argues that these conceptions of the policy process fail to adequately reflect the real-world dynamism and complexity of the processes and practices of social policy-making and implementation. In this context, psychological evidence needs to be seen as one type of evidence (amongst many others). In turn this requires researchers to take account of broader political processes that favour certain types of knowledge and disparage others. Rather than be regarded as objective and scientific, policy in this characterisation is regarded as a motivated form of politics. This multi-layered, multi-level hybrid structure is not immediately amenable to the well-intentioned interventions of psychologists. While the tendency of many psychologists is to overestimate the impact that we can have upon policy formation and implementation, there are examples where psychological theory and research has fed directly into UK policy developments in recent years. This paper draws on the recent Improving Access to Psychological Therapies (IAPT) initiative and the work of personality researcher Adam Perkins on the UK’s social security system to ask whether psychology has a sufficiently elaborated sense of its own evidence base to legitimately seek to influence key national areas of public policy. The article cautions against dramatic changes to policy predicated upon any one reading of the variegated and, at times, contradictory psychological evidence base. It concludes that, in order to meaningfully contribute to the policy development process in a way which increases equality and social justice, psychologists need to be more strategic in thinking about how their research is likely to be represented and misrepresented in any particular context. Finally some possible directions for psychologists to take for a more meaningful relationship with policy are suggested.
Towards the establishment of renewable energy technologies' market: An assessment of public acceptance and use in Pakistan
Authors: Shakeel Shah Rukh , Rahman Saleem ur
Published: August 2018

Adoption of renewable energy technologies is a complex and intricate process affected by a multitude of factors. The objective of this study is to examine the factors influencing consumers' intention to use renewable energy technologies for household usage in Pakistan. In order to understand the adoption behaviour, we have extended the actual framework of the theory of planned behaviour by integrating three additional factors, i.e., environmental concern, cost, and awareness. The findings of this research are based on primary data collected from 244 households in the twin cities of Islamabad and Rawalpindi through survey questionnaires. The proposed hypotheses were then tested and analysed using structural equation modelling. The results reveal that factors such as subjective norm, perceived behavioural control, and attitude positively influence consumers' intention to use renewable energy technologies in Pakistan, whereas cost has the opposite effect. Interestingly, awareness and environmental concern were found to be insignificant. The results of this study highlight the need to increase environmental awareness, frame innovative financing mechanisms, and address the benefits that renewable energy technology offers, all through an integrative and coherent effort.
Improving the dynamic performance of grid connected wind farm using new SMES switching technique
Authors: Okedu Kenneth E.
Published: August 2018

Due to the uncertain nature of wind energy, the effective operation of grid connected wind farms is quite a challenge for grid operators. The stipulated grid requirements for frequency and voltage control must be satisfied to avoid the shutdown of grid networks during periods of dynamic grid disturbance. This paper tends to improve the dynamic performance of a grid network consisting of nuclear and thermal turbines that are tied to a wind farm that is made up of fixed speed squirrel cage induction generator wind turbine type. A supermagnetic energy storage (SMES) system is connected to the terminal of the wind farm in order to achieve smoothing of the distorted wind turbine variables so that steady power supply could be maintained during periods of grid disturbance. A new control strategy to improve the performance of the traditional SMES is proposed by integrating a parallel DC-DC chopper in the circuitry of the voltage source converter. The responses of the proposed control strategy for SMES were compared with the traditional SMES scheme during grid disturbance under the same conditions of wind speed. The simulation results in power system computer aided design and electromagnetic transient including the DC platform show the improved performance of the grid variables considering the proposed scheme for SMES.