bluuebunny/crossref_metadata_2025_split huggingface dataset:
Advances in heart regeneration based on cardiomyocyte proliferation and regenerative potential of binucleated cardiomyocytes and polyploidization
Authors: Leone Marina , Engel Felix B. 
Published: June 2019

Abstract
One great achievement in medical practice is the reduction in acute mortality of myocardial infarction due to identifying risk factors, antiplatelet therapy, optimized hospitalization and acute percutaneous coronary intervention. Yet, the prevalence of heart failure is increasing presenting a major socio-economic burden. Thus, there is a great need for novel therapies that can reverse damage inflicted to the heart. In recent years, data have accumulated suggesting that induction of cardiomyocyte proliferation might be a future option for cardiac regeneration. Here, we review the relevant literature since September 2015 concluding that it remains a challenge to verify that a therapy induces indeed cardiomyocyte proliferation. Most importantly, it is unclear that the detected increase in cardiomyocyte cell cycle activity is required for an associated improved function. In addition, we review the literature regarding the evidence that binucleated and polyploid mononucleated cardiomyocytes can divide, and put this in context to other cell types. Our analysis shows that there is significant evidence that binucleated cardiomyocytes can divide. Yet, it remains elusive whether also polyploid mononucleated cardiomyocytes can divide, how efficient proliferation of binucleated cardiomyocytes can be induced, what mechanism regulates cell cycle progression in these cells, and what fate and physiological properties the daughter cells have. In summary, we propose to standardize and independently validate cardiac regeneration studies, encourage the field to study the proliferative potential of binucleated and polyploid mononucleated cardiomyocytes, and to determine whether induction of polyploidization can enhance cardiac function post-injury.
High boost‐ratio bidirectional converter for interfacing low‐voltage battery energy storage system to a DC bus
Authors: Muchina Eliud G. , Masike Lebogang , Njoroge Gitau Michael 
Published: June 2019

Supply and demand mismatches in renewable energy systems are addressed by integrating battery banks. Selecting battery bank terminal voltage to match DC‐bus voltage (350–450 V for single‐phase AC loads), necessitates employing battery banks with long‐string connections along with their attendant shortcomings. To employ short‐string battery banks, high‐boost‐ratio bidirectional interfaces are required between the DC‐bus and battery bank. Current literature lacks a single source where high‐boost‐ratio converters’ are categorised and their strengths and weaknesses identified. Comprehensive literature review is hence carried out to determine attributes of various high‐boost‐ratio DC–DC converters and also categorise them. The key attributes of a topology to interface battery storage to a DC‐bus are determined. Based on these a bidirectional tapped‐inductor boost converter emerges as the best candidate. Moreover, in order to regulate output voltage, voltage‐gain versus duty‐ratio characteristics should not be very steep. Since battery terminal voltage varies with state‐of‐charge, closed‐loop control is necessary. Converter's small‐signal transfer‐functions are derived and a two‐loop controller to regulate output voltage and inductor current while allowing bidirectional power flow designed. A novel bidirectional passive lossless snubber circuit is employed to clamp the voltage spikes across the active switches, without altering the normal operation of the converter.
Zero‐voltage soft‐switching DC–DC converter‐based charger for LV battery in hybrid electric vehicles
Authors: Sayed Khairy 
Published: June 2019

This study presents the implementation of a DC‐DC power converter for battery charging from 200 V lithium‐ion or nickel metal hydride (NiMH) battery to lead‐acid battery (typically 12 V) utilised in hybrid vehicles such as Toyota Prius. For hybrid car, a low‐voltage (LV) battery is utilised to power air conditioner, main lights, and different actuators in engine controlling unit etc. The LV battery is usually recharged by car alternator. For the sake of improving fuel efficiency, it is important to regulate charging by using the charging control scheme, where the battery charging is implemented in deceleration interval avoiding the acceleration interval of the car. The hybrid car is equipped with a high‐voltage (HV) NiMH battery. The lead‐acid LV battery is charged from the HV storage battery. The advantage of this charging method is recognised not only to replace the alternator from the car, but also to make efficient braking touching for the car driver, because the regenerative breaking recovered energy can be totally absorbed in the main HV battery. Moreover, the overall efficiency could be easily improved because the total efficiency of charging DC‐DC circuit is greater than that of the car alternator.
Control delay compensation scheme based on non‐instantaneous loading and pulse‐width equivalence for active damping of LCL‐type inverters
Authors: Zhu Kunlong , Sun Pengju , Wang Lin , Zhou Luowei , Du Xiong 
Published: June 2019

Active damping (generally by the feedback of capacitor current) is an effective solution to the resonance peak of LCL‐type grid‐connected inverters. However, the damping performance is significantly affected by the computation and pulse‐width modulation delays in the digital control system, which results in poor system robustness. Moreover, the phase lag would be introduced by these control delays, leading to the constrained bandwidth and low‐frequency gain of control loop. In this study, a novel compensation method based on non‐instantaneous loading and pulse‐width equivalence is proposed to completely eliminate the computation delay without any reliability problem. Moreover, compared to the traditional strategies, the proposal can be extended to most two‐level converters because of its simplicity. Finally, the validity of the proposed method is confirmed by the experimental results from a 3 kW single‐phase grid‐connected inverter with an LCL filter.
Dusty disk winds at the sublimation rim of the highly inclined, low mass young stellar object SU Aurigae
Authors: Labdon Aaron , Kraus Stefan , Davies Claire L. , Kreplin Alexander , Kluska Jacques , Harries Tim J. , Monnier John D. , ten Brummelaar Theo , Baron Fabien , Millan-Gabet Rafael , Kloppenborg Brian , Eisner Joshua , Sturmann Judit , Sturmann Laszlo 
Published: June 2019

Context. T Tauri stars are low-mass young stars whose disks provide the setting for planet formation. Despite this, their structure is poorly understood. We present new infrared interferometric observations of the SU Aurigae circumstellar environment that offer resolution that is three times higher and a better baseline position angle coverage than previous observations.
Aims. We aim to investigate the characteristics of the circumstellar material around SU Aur, constrain the disk geometry, composition and inner dust rim structure.
Methods. The CHARA array offers unique opportunities for long baseline observations, with baselines up to 331 m. Using the CLIMB three-telescope combiner in the K-band allows us to measure visibilities as well as closure phase. We undertook image reconstruction for model-independent analysis, and fitted geometric models such as Gaussian and ring distributions. Additionally, the fitting of radiative transfer models constrain the physical parameters of the disk. For the first time, a dusty disk wind is introduced to the radiative transfer code TORUS to model protoplanetary disks. Our implementation is motivated by theoretical models of dusty disk winds, where magnetic field lines drive dust above the disk plane close to the sublimation zone.
Results. Image reconstruction reveals an inclined disk with slight asymmetry along its minor-axis, likely due to inclination effects obscuring the inner disk rim through absorption of incident star light on the near-side and thermal re-emission and scattering of the far-side. Geometric modelling of a skewed ring finds the inner rim at 0.17 ± 0.02 au with an inclination of 50.9 ± 1.0° and minor axis position angle 60.8 ± 1.2°. Radiative transfer modelling shows a flared disk with an inner radius at 0.18 au which implies a grain size of 0.4 μm assuming astronomical silicates and a scale height of 15.0 at 100 au. Among the tested radiative transfer models, only the dusty disk wind successfully accounts for the K-band excess by introducing dust above the mid-plane.
Inhibition of Type 1 Iodothyronine Deiodinase by Bisphenol A
Authors: da Silva Maurício Martins , Gonçalves Carlos Frederico Lima , Miranda-Alves Leandro , Fortunato Rodrigo Soares , Carvalho Denise P. , Ferreira Andrea Claudia Freitas 
Published: June 2019

AbstractPlastics are ubiquitously present in our daily life and some components of plastics are endocrine-disrupting chemicals, such as bisphenol A and phthalates. Herein, we aimed to evaluate the effect of plastic endocrine disruptors on type 1 and type 2 deiodinase activities, enzymes responsible for the conversion of the pro-hormone T4 into the biologically active thyroid hormone T3, both in vitro and in vivo. Initially, we incubated rat liver type 1 deiodinase and brown adipose tissue type 2 deiodinase samples with 0.5 mM of the plasticizers, and the deiodinase activity was measured. Among them, only BPA was capable to inhibit both type 1 and type 2 deiodinases. Then, adult male Wistar rats were treated orally with bisphenol A (40 mg/kg b.w.) for 15 days and hepatic type 1 deiodinase and brown adipose tissue type 2 deiodinase activities and serum thyroid hormone concentrations were measured. In vivo bisphenol A treatment significantly reduced hepatic type 1 deiodinase activity but did not affect brown adipose tissue type 2 deiodinase activity. Serum T4 levels were higher in bisphenol A group, while T3 remained unchanged. T3/T4 ratio was decreased in rats treated with bisphenol A, reinforcing the idea that peripheral metabolism of thyroid hormone was affected by bisphenol A exposure. Therefore, our results suggest that bisphenol A can affect the metabolism of thyroid hormone thus disrupting thyroid signaling.
FACTOR VIII MEDIATES BINDING OF FACTOR IX TO STIMULATED PLATELETS
Authors: Muntean W , Leschnik B 
Published: June 2019

In previous work we have shown that factor VII! binds to phospholipids of the membrane of stimulated platelets and that von Willebrand factor is not required for binding of factor VIII to platelets. Since factor VIII is a cofactor in the activation of factor X by factor IX, we investigated whether factor VIII enhances binding of factor IX to the platelet surface.Factor VIII and factor IX were purified by immunoadsorbent chromatography using specific rabbit antibodies. Washed human platelets (250/nl final concentration) stimulated by human thrombin and collagen were incubated with barbiturate buffer, or with purified factor IX (1 U/ml final concentration), or with factor IX (1 U/ml) in the presence of factor VIII (1 U/ml). Washed and stimulated platelets were also incubated with factor VIII and IX as above in the presence of different amounts of CaCl2. Platelets were then washed again and lysed by sonication. Factor VIII:Ag (immunoradiometric assay) and factor IX:Ag (ELISA) were measured in the platelet lysate prior to and after incubation of the lysate with phospholipase C.Platelet bound IX:Ag was significantly higher after incubation of stimulated platelets with factor IX in the presence of factor VIII than after incubation of platelets with buffer or with factor IX alone. CaCl2 proved to be essential for binding of factor IX to platelets even in the presence of factor VIII, but CaCl2 was not required for binding of factor VIII to platelets. Measurable VIII :Ag and IX:Ag increased significantly after incubation of the platelet lysate with phospholipase C.Our data suggest that factor VIII mediates binding of factor IX to phospholipids or receptors containing phospholipids on the membrane of stimulated platelets and thereby contributes to the assembly of the factor X activating complex on the platelet surface.
SEARCH FOR AND USE OF RESTRICTION FRAGMENT LENGTH POLYMORPHISMS (RFLPs) IN AND AROUND THE HUMAN FACTOR IX GENE
Authors: Liddell M B , Anson D S , Lillicrap D P , Peake I R 
Published: June 2019

5 previously described RFLPs within the factor IX gene have been used for family studies (carrier detection) in 10 haemophilia B kindred. In all DNA from 91 individuals, including 25 obligate or possible carriers, was analysed by digestion with TaqI and XmnI and probing with the intragenomic probe VIII (all probes were provided by Professor G. G. Brownlee, Oxford). When noninformative, additional RFLPs (DdeI;probe XIII and MspI;probe II) were used. Of 12 possible carriers, 11 were diagnosed (6 as carriers, 5 normal). Of the confirmed carriers (6 diagnosed, 13 obligate) 15 were informative (heterozygous and phase known), and the overall incidence of heterozygosity was 72%. The recently reported BamHI RFLP was not found to be useful ( <1.0% frequency).Further RFLPs in and flanking the factor IX gene were sought by two procedures. Firstly cosmid pCHIXα, containing a 40kb insert including the 3' end of the factor IX gene and stretching some 35kb 3' to the gene was used as a large probe, with repetitive sequences being blocked by preannealing the probe with an excess of sonicated, denatured human DNA (Litt and White, PNAS 82, 6206). Results with 25 restriction enzymes (covering an estimated 1038 nucleotides) and DNA from 7 unrelated females were obtained, but only one low frequency PvuII RFLP (frequency about 1%) was identified. Similar experiments with further cosmid probes 3' to the gene are underway. The second technique was developed to analyse small DNA fragments (<1.0kb) generated by frequently cutting restriction enzymes. These fragments were separated on 3.5% polyacrylamide/0.5% agarose composite gels and then electroblotted onto hybond-N. Fragments of 150bp were readily visualised by this procedure. 3 frequently cutting enzymes have been used (Hinfl, Rsal and Mbol), and the blots probed with a factor IX c-DNA probe, or a unique sequence subclone of cosmid pCHIXα. To date no RFLPs have been identified. This search for further useful RFLP has illustrated the paucity of detectable sequence variation within this region of the X-chromosome.
EFFECT OF ELASTASE INDUCED CLEAVAGE OF VON WILLEBRAND FACTOR (vWf) ON ITS STRUCTURE AND FUNCTION
Authors: Howard M A , Coghlan M , Firkin B G 
Published: June 2019

A proteolytic product of vWf termed fast migrating protein (vWf:FMP) has been identified using crossed immunoelectrophoresis (CIE) in normal serum and in the plasma from patients with disseminated intravascular coagulation (DIC). A fragment of vWf antigen (vWf:Ag) migrating to a similar position on CIE as vWf:FMP results from digestion of vWf:Ag with polymorphonuclear cells (PMNC). Since parallels exist between the conditions for generation of vWf:FMP by PMNC and elastase release by these cells the effect of purified elastase from porcine pancrease on vWf was investigated.VWf was purified from plasma using polyethylene glycol, ammonium sulphate and zinc acetate precipitation, high speed centrifugation and elution from column of Sepharose 4B-CL. A fraction rich in vWf was radiolabelled with 125-Iodine to spike the purified preparation of vWf in order to increase the sensitivity of the protein detecting systems.A mixture of radiolabelled and non-labelled purified vWf was incubated with elastase at concentrations ranging from 2.5 to 40 U/ml for periods of 0-48 hours. Modifications of the structure were assessed by SDS-agarose multimeric analysis, SDS-polyacrylamide electrophoresis and CIE. Alterations of function were quantitated by antigen levels, ristocetin (RCof) and botrocetin (BCoF) cofactor assays and a binding assay to fixed washed platelets in the presence of ristocetin or botrocetin.These investigations show, 1. all but the highest molecular weight multimers of vWf are present when elastase has cleaved vWf such that no intact 240K subunit is present. 2. an intact 240K subunit is not essential for RCoF and BCoF activity or for ristocetin or botrocetin induced binding to platelets.
INCREASED ADHESIVE PROPERTIES OF THE CARBOHYDRATE-MODIFIED VON WILLEBRAND FACTOR (CHO-VWF): CRITICAL ROLE OF THE MULTIMERIC STRUCTURE AND CORRELATION WITH PLATELET AGGREGATION
Authors: Federici A B , De Romeuf C , De Groot P G , Mannucci P M , Samor B , Lombardi R , D'Alessio P , Mazurier C , Sixma J J 
Published: June 2019

We have reexplored the role of the carbohydrate moiety (CHO) on the von Willebrand Factor (vWF) structure and function by critically evaluating its different purification steps and modifications in CHO content by specific enzymes. Structural and functional assays have been evaluated separately in each laboratory (Milano and Lille) and jointly in Utrecht during several organized experiments. Under our conditions, the CHOVWFs obtained were characterized by less than 5% of sialic acid "(Neu)asevWF" and about 45% of D-Galactose "(Neu-Gal)ase-vWF" remaining, by increased electrophoretic mobility without any significant losses of the high molecular weight multimers and by their capacity to induce spontaneous aggregation in normal platelet rich plasma (PRP). Platelet adhesion to these different CHO-vWFs was tested in the flat chamber devised by Sakariassen in the presence of different subendothelial matrices and data expressed as the percentage of the surface covered by platelets. The blood reconstituted with different plasma samples showed the following percentual values of surface coverage (mean ± SD):- Normal plasma = 15 ± 3.8- Severe vWd plasma = 4 ± 1.9- SvWd pl + Native vWF = 14 ± 2.8- SvWd pl + (Neu) ase-vWF = 23 ± 3.5- SvWd pl + (Neu-Gal) ase-vWF = 19 ± 2.9This significantly increased adhesion to the subendothelium of the CHO-vWFs corresponded to the spontaneous aggregation present in normal PRP but it disappeared when the multimeric structure was damaged by in vitro proteolysis and/or by storage conditions (changes in temperature and freezing and thawing). From these results we may conclude that removal of terminal sugars enhances not only platelet-vWF interactions, but also platelet adhesion to the subendothelium.
LOCALIZATION OF THE PLATELET-BINDING AND HEPARIN-BINDING DOMAINS OF BOVINE VON WILLEBRAND FACTOR
Authors: Kirby Edward P , Mascelli Mary Ann , Silverman Carol , Karl Daniel W 
Published: June 2019

Bovine von Willebrand Factor (vWF) binds directly to human platelets and also to heparin-agarose. Cleavage of vWF with Protease I, a metalloenzyme isolated from the venom of the western diamondback rattlesnake, produces two major fragments with apparent Mr of 250 kD and 200 kD. The 200 kD fragment competes with native vWF for binding to the GPIb-associated vWF receptor on formalin-fixed human platelets and has weak platelet-agglutinating activity. It is composed of three polypeptide chains of apparent Mr of 97 kD, 61 kD, and 35 kD. Monoclonal antibodies #2 and H-9, which inhibit binding of vWF to a GPIb-associated receptor of platelets, recognize the 200 kD fragment.Modification of vWF with ^5x-la.beled. Bolton-Hunter reagent (I*-BHR) causes inhibition of platelet-agglutinating activity at very low levels of incorporation. Modification of less than 2% of the amino groups in vWF causes 50% loss of platelet agglutinating activity and a decreased affinity of vWF for binding to platelets. Labeling with I*-BHR does not block binding to heparin-agarose, even when 5-10% of the amino groups are modified. Differential labeling at pH 7.0 and pH 8.5, followed by proteolytic fragmentation with Protease I, suggests that it is the modification of amino groups on the 200 kD fragment which is responsible fpr the decrease in platelet binding activity. Modification of the 97 kD peptide chain is best correlated with this loss of platelet binding activity.Heparin inhibits the agglutination of human platelets by bovine vWF. The 200 kD fragment of vWF binds both to platelets and to heparin-agarose. These observations suggest that the heparin-binding and platelet-binding domains of vWF, although distinct from one another, reside in the same region of the vWF molecule. The platelet-binding domain contains a small number of very reactive amino groups which are required for vWF binding to human platelets.These studies were supported by a grant from the National Institutes of Health (#HL27993).
IDENTIFICATION AND FURTHER CHARACTERIZATION OF TYPE IIE VON WILLEBRAND DISEASE
Authors: Triplett D , Muagrave K , Daniels T , Bowie E J W 
Published: June 2019

Type IIE von Willebrand disease has previously been identified in a single family with two affected members. We have identified a second family with five affected individuals. The pattern of inheritance is autosomal dominant and the clinical picture is characterized by mild mucocutaneous bleeding. Laboratory results for affected patients: VIII:C ranged from .62 u/ml to 1.0 u/ml, VWD antigen 2.0 u/ml to 4.75 u/ml, and ristocetin cofactor activity 0.04 u/ml to .32 u/ml. Bleeding times, PT and APTT results were within normal ranges.Multimeric analysis of both citrated plasma and platelet lysates utilizing sodium dodecyl sulfate-polyacrylamide electrophoresis was characterized by a decrease of the largest oligomers and the individual multimers were abnormal with a single identifiable band. Plasma samples collected in the presence of a variety of inhibitors had no effect on the multi-meric pattern. Intravenous infusion of DDAVP (.3 ug/kg of body weight) resulted in a slight increase in the highest molecular weight oligomers but no change in the ristocetin cofactor activity or individual multimeric patterns.
HYPOTHYROIDISM AND ACQUIRED VON WILLEBRAND'S DISEASE
Authors: Preston F E , Greaves M , Sampson B , Kernoff P B A , Savidge G , Bax N 
Published: June 2019

A diagnosis of type IA von Willebrand's disease was made in three patients presenting with a mild bleeding tendency. Previously unrecognised hypothyroidism was also confirmed in two patients. In the third, hypothyroidism was diagnosed four years after initial presentation. In all three patients, thyroxine therapy was associated with correction of the haemostatic defect and resolution of the bleeding tendency.The association of von Willebrand's disease and hypothyrodism prompted us to examine the relationship between thyrotrophin (TSH), T3, T4 and components of the factor VIII complex in 12 patients with clinical and biochemical hypothyroidism. Factor IX was also studied. Mean VIII:C (measured by 2 stage assay) was 0.90 u/ul (range 0.55 - 1.14); mean vWF:Ag 0-83 u/ul (range 0.44 - 1.64); mean VIII:Rcof 0.75 (range 0.45 - 1.55); mean factor IX 0.72 (range 0.39 - 1.19). Multimeric analysis of vWF:Ag performed in samples from 8 patients was normal. VIII:Rcof levels were significantly lower than those of normal controls. A significant inverse correlation was obtained between TSH and factor IX and T4 and vWF:Ag. Although there is a definite inverse relationship between TSH and factor IX, this is not evident with respect to factor VIII and a different mechanism is probably responsible for the modest reduction of vWF:Ag and the occurrence of clinically-evident von Willebrand's disease which we have demonstrated in a small proportion of hypothyroid patients.