bluuebunny/crossref_metadata_2025_split huggingface dataset:
Uniqueness typing for functional languages with graph rewriting semantics
Authors: Barendsen Erik , Smetsers Sjaak 
Published: May 2019

We present two type systems for term graph rewriting: conventional typing and (polymorphic) uniqueness typing. The latter is introduced as a natural extension of simple algebraic and higher-order uniqueness typing. The systems are given in natural deduction style using an inductive syntax of graph denotations with familiar constructs such as let and case.The conventional system resembles traditional Curry-style typing systems in functional programming languages. Uniqueness typing extends this with reference count information. In both type systems, typing is preserved during evaluation, and types can be determined effectively. Moreover, with respect to a graph rewriting semantics, both type systems turn out to be sound.
Prevalence and molecular characterization of multidrug-resistant M. tuberculosis in Jiangxi province, China
Authors: Luo Dong , Chen Qiang , Xiong Guangchu , Peng Yiping , Liu Tao , Chen Xiaowen , Zeng Lingbing , Chen Kaisen 
Published: May 2019

AbstractMultidrug-resistant Mycobacterium tuberculosis (MDR-TB) is a severe health threat to human beings; however, the epidemic and molecular characteristics exist along with the change in the geographic environment and genealogy. Jiangxi province is located in southeast China, which is a high-MDR-TB burden area. Rifampin (RIF) and isoniazid (INH) are the most important first-line anti-tuberculosis drugs. The major drug target genes include rpoB for RIF and katG, inhA, and ahpC for INH. To determine the frequency and distribution of mycobacterial mutations in these genes, we sequenced specific genes of M. tuberculosis that are associated with resistance to RIF and INH in 157 phenotypic MDR isolates. At the same time, RD105 DTM-PCR and 15 loci MIRU-VNTR were performed to demonstrate the genetic lineage. It was shown that the Beijing genotype was predominant (84.1%) among these strains. The results also showed mutations within the 81 bp core region of rpoB in 93.6% of strains and mutations in a structural gene (katG) and two regulatory regions (the promoter of inhA and intergenic region of oxyR-ahpC) were shown in 88.5% of phenotypic MDR isolates. There were no significant differences in codon mutations between the Beijing and non-Beijing genotypes, as well as the clustered and no-clustered strains. The most prevalent mutations involved in RIF and INH were Ser531Leu in rpoB (55.4%) and Ser315Thr in KatG (56.1%), respectively. There was no significant difference in RIF and INH resistance between MDR-TB and other drug-resistant tuberculosis (DR-TB). The results demonstrated that some MDR-TB patients are predicted to have recent transmission.
Regulating response and leukocyte adhesion of human endothelial cell by gradient nanohole substrate
Authors: Huang Li-Hua , Cui Long-Hui , Kim Dae Hwan , Joo Hyung Joon , Seo Ha-Rim , Choi Seung-Cheol , Noh Ji-Min , Lee Kyu Back , Hong Soon Jun 
Published: May 2019

AbstractUnderstanding signals in the microenvironment that regulate endothelial cell behavior are important in tissue engineering. Although many studies have examined the cellular effects of nanotopography, no study has investigated the functional regulation of human endothelial cells grown on nano-sized gradient hole substrate. We examined the cellular response of human umbilical vein endothelial cells (HUVECs) by using a gradient nanohole substrate (GHS) with three different types of nanohole patterns (HP): which diameters were described in HP1, 120–200 nm; HP2, 200–280 nm; HP3, 280–360 nm. In results, HP2 GHS increased the attachment and proliferation of HUVECs. Also, gene expression of focal adhesion markers in HUVECs was significantly increased on HP2 GHS. In vitro tube formation assay showed the enhancement of tubular network formation of HUVECs after priming on GHS compared to Flat. Furthermore, leukocyte adhesion was also reduced in the HUVECs in a hole-diameter dependent manner. To summarize, optimal proliferations with reduced leukocyte adhesion of HUVECs were achieved by gradient nanohole substrate with 200–280 nm-sized holes.
5-Oxo-1-[(2,3,6,7-tetramethoxy-9-phenanthrenyl)methyl]-L-proline Inhibits Hepatitis C Virus Entry
Authors: Nguyen Lap P. , Park Chorong , Luong Trang T. D. , Park Eun-Mee , Choi Dong-Hwa , Han Kang Min , Mai Han N. , Nguyen Huu C. , Lim Yun-Sook , Hwang Soon B. 
Published: May 2019

AbstractHepatitis C virus (HCV) is the major causative agent of chronic liver diseases, including liver cirrhosis and hepatocellular carcinoma. The recent development of highly effective direct-acting antivirals (DAAs) has revolutionized the treatment of HCV patients. However, these DAAs are exorbitantly expensive for the majority of HCV patients worldwide. Moreover, these drugs still show genotypic difference in cure rate and have some resistant-associated variants. Tylophorine, a natural compound derived fromTylophora indicaplants, is known to have anti-inflammatory and anti-cancerous growth activities. In the present study, we showed that two tylophorine intermediates, 5-Oxo-1-[(2,3,6,7-tetramethoxy-9-phenanthrenyl) methyl]-L-proline (O859585) and 2,3,6,7-tetramethoxy-9-phenanthrenecarboxylic acid (T298875), displayed anti-HCV activity with an EC50of 38.25 µM for T298875 and 29.11~35.3 µM for O859585 in various HCV genotypes. We demonstrated that O859585 efficiently blocked HCV attachment by neutralizing free viral particles without affecting other stages of the HCV life cycle and interferon stimulation. O859585 interrupted binding between HCV E2 and CD81. Of note, co-treatment of O859585 with either interferon alpha (IFNα) or sofosbuvir exerted either an additive or synergistic antiviral activity in HCV-infected cells with no measurable effect on cell viability. Most importantly, O859585 in combination with IFNα and sofosbuvir exhibited synergistic effects on anti-HCV activity in primary human hepatocytes. Collectively, these data suggest that O859585 may be a novel antiviral agent for HCV therapy.
(Neo)adjuvant chemotherapy and interdigitated split-course hyperfractionated radiation in high risk soft tissue sarcoma – Results from a large single-institution series
Authors: Nevala Riikka , Tukiainen Erkki , Tarkkanen Maija , Böhling Tom , Blomqvist Carl , Sampo Mika 
Published: May 2019

AbstractA single-institution series using a (neo)adjuvant chemotherapy and interdigitated hyperfractionated split-course radiation therapy (CRT) treatment protocol for soft tissue sarcoma was reviewed. Our specific aims were to study recurrence rates and long-term toxicity. Between 1998 and 2016, 89 patients with non-metastatic soft tissue sarcoma were treated with surgery combined with six courses of doxorubicin and ifosfamide and hyperfractionated radiation therapy (42–60 Gy/1.5 Gy twice daily). Patients were considered being at high risk if tumour malignancy grade was high and the tumour fulfilled at least two of the following criteria: size >8 cm, presence of necrosis or vascular invasion. The mean age of the patients was 50.7 years. With a median follow-up of 5.4 years for survivors, the local control rate was 81.4%. Six (7%) patients progressed during neoadjuvant CRT. Seven (8%) patients discontinued the treatment due to toxicity. Eighty-six patients were operated and three (3%) of these developed a long-term complication. The estimated metastasis-free survival was 47.6% and overall survival 53.0% at five years. The limb-salvage rate was 93%. The limb-salvage rate, local control and complication rates were good in these patients with high risk soft tissue sarcoma. Metastases-free survival and overall survival rates were less satisfactory, reflecting the aggressive nature of these tumours.
Liposomes as models for membrane integrity
Authors: Routledge Sarah J. , Linney John A. , Goddard Alan D. 
Published: May 2019

Abstract
Biological membranes form the boundaries to cells. They are integral to cellular function, retaining the valuable components inside and preventing access of unwanted molecules. Many different classes of molecules demonstrate disruptive properties to the plasma membrane. These include alcohols, detergents and antimicrobial agents. Understanding this disruption and the mechanisms by which it can be mitigated is vital for improved therapeutics as well as enhanced industrial processes where the compounds produced can be toxic to the membrane. This mini-review describes the most common molecules that disrupt cell membranes along with a range of in vitro liposome-based techniques that can be used to monitor and delineate these disruptive processes.
Plasma environment effects on K lines of astrophysical interest
Authors: Deprince J. , Bautista M. A. , Fritzsche S. , García J. A. , Kallman T. , Mendoza C. , Palmeri P. , Quinet P. 
Published: May 2019

Aims. In the context of accretion disks around black holes, we estimate plasma-environment effects on the atomic parameters associated with the decay of K-vacancy states in highly charged iron ions, namely Fe XVII– Fe XXV.Methods. Within the relativistic multiconfiguration Dirac–Fock (MCDF) framework, the electron–nucleus and electron–electron plasma screenings were approximated with a time-averaged Debye–Hückel potential.Results. Modified ionization potentials, K thresholds, wavelengths, radiative emission rates, and Auger widths are reported for astrophysical plasmas characterized by electron temperatures and densities in the ranges 105 − 107K and 1018 − 1022cm−3, respectively.Conclusions. We conclude that the high-resolution microcalorimeters on board future X-ray missions such as XRISM and ATHENA are expected to be sensitive to the lowering of the iron K edge due to the extreme plasma conditions occurring in accretion disks around compact objects.
Absence of Fibroblast-Induced Fibrin Clot Retraction in a Patient with Glanzmann’s Thrombasthenia and Abnormal Wound Healing
Authors: Gaetano G. de , Remuzzi G. , Balconi G. , Donati M. B. 
Published: May 2019

Platelets and fibroblasts from normal individuals induce fibrin clot retraction(FCR). Absence of platelet-induced FCR is a characteristic abnormality of Glanzmann’s thrombasthenia (GT) patients. The purpose of this study vas to evaluate whether fibroblasts from a 16-year old girl with severe GT (Thromb. Haemost. 1976, 36, 286) would induce FCR.Fibroblast culture was established from skin biopsy from the inner arm of the patient; fibroblasts were grown and FCR was evaluated as described previously (Europ. J. Cancer 1976, 12, 823). No clot retraction was observed in the samples containing GT fibroblasts during a 24-hour observation period. In control samples FCR started after about 3 hours and appeared to be completed within 12 hours (70–85%).Since fibrin-fibroblast interaction could play a role in normal tissue repair, the process of healing of the wound produced in this patient by the skin biopsy was followed. Neither haemorrhagic complications nor infections occurred during the first 10 days after the biopsy; at that time stiches were removed and the lips of the wound appeared to be well in line. However, abnormal tissue repair (lips swollen, out of the line and interwoven by recent granulation tissue) was evident 20 days later and persisted till the last outpatient control (6 months after biopsy).These results would suggest that in GT the cellular abnormality, as indicated by absent FCR, is not restricted to platelets. Whether the abnormal platelet and fibroblast interaction with fibrin might be somehow related to defective wound healing following skin biopsy is not yet known.
Relationship Between Aggregation and Prostaglandin (PG)-Biosynthesis in Rat Platelet Rich Plasma (PRP)
Authors: Bult H. , Bragt P. C. , Bonta I. L. 
Published: May 2019

The importance of PG biosynthesis in aggregation has been studied by comparing PRP from normal and essential fatty acid deficient (EFAD) rats. The latter show a marked lack of the PG precursor, arachidonic acid (AA).No differences were observed in aggregation with collagen (from 10 μg/ml), ADP (from 0.8 μM) or the PG-endoperoxide PGH2 (1 μg/ml). PGH2 induced only a small, transient aggregation. However, with a collagen dose that produced a 50% response in normal PRP, the aggregation of EFAD PRP was 94% reduced. This correlated with reduced (84–89%) biosynthesis of thromboxane A2 and PGE-like material (PGE), both assessed by bioassay. The PG synthetase of EFAD PRP was unaltered, since PGE and malondialdehyde production were normal when exogenous AA was added. AA, up to 0.33 mM, did not aggregate normal PRP, but high amounts of PGE were formed.These results indicate that internal PG biosynthesis is only essential for aggregation with threshold doses of collagen. At higher collagen doses endogenous PG production does not seem to be important for aggregation. It is unlikely that residual formation of PG-endoperoxides in EFAD PRP, at high doses of collagen, is sufficient for a normal aggregation, since normal rat platelets form PG-endoperoxides from exogenous AA without aggregation.
Evaluation of Urokinase Therapy for Cerebrovascular Occlusive Diseases
Authors: Abe T. , Kazama M. , Maruyama I. , Fukuda R. 
Published: May 2019

Urokinase (UK) was administered to 55 cases, of possibly occlusive cerebrovascular accidents and its clinical effects were analyzed. The indication was considered by the elapsing time from the onset, the gravity of clinical signs, the localization and size of brain damage, the angiographical feature and the supposed pathohistological changes in brain. UK administration was controlled mainly by PT, PTT, fibrinogen-, FDP-content, ELT, platelet count and its functions as the monitoring parameters. Average doses of UK for adults, 30,000 IU twice daily, were continued for the first week, and then decreased by half every two or three days. The thrombolytic treatment was maintained for two to three weeks. Administration of Warfarrin or dextran sulfate was started several days before the discontinuation of UK therapy and continued for some weeks.Depending on the response of the patients to this therapy, they were divided into five classes;a) clinical improvement with visible resolution of thrombi proved by angiography or computerized tomography (14 cases),b) clinical improvement without visible agniographic findings (35 cases),c) no improvement in clinical and laboratory findings (3 cases),d) clinical improvement with worsening of partial clinical signs (3 cases), ande) clinical exacerbation without any effect (no case).
Simulation of Coupled Enzyme Assays for a New Determination of Plasminogen Via the Clotting Time
Authors: Richter O. , Jacobi E. 
Published: May 2019

The enzymatic assay for the determination of plasminogen via the clotting time (JACOBI et al., Dtsch. med. Wochenschr. 101 (1976) 1220–1222 0.2 ml plasminogen reagent (test-kit Behringwerke/Hoechst AG) 0.1 ml plasma, diluted 1:100, incubation time 3 min. 37°C0.05 ml thrombine (3 NIH U/ml), clotting timeis based on the following sequence of reactions: (plasminogen reagent = fibrinogen, bovine plasminogen and streptokinase, which does not react with bovine plasminogen) human plasminogen and streptokinase form an activator, which converts bovine plasminogen to bovine plasmin, which splits fibrinogen during the incubation time. The thrombine clotting time of the resulting mixture containing fibrinogen and fibrinogen degradation products depends on the amount of bovine plasmin in the assay, which is in turn a function of human plasminogen concentration. The assay is described by a kinetic model in terms of non-linear differential equations. On the basis of this model the clotting time can be computed as a function of the parameters of the assay: concentration of fibrinogen, human plasminogen, bovine plasminogen and incubation time. By computer simulation an optimal parameter set is obtained for which the resulting calibration curve is linear and not sensitive against the variances of the reagent. Furtermore, the model gives a detailed insight into the mechanism involved in the interaction of human plasminogen, fibrinogen, bovine plasminogen and thrombine.
Two-Dimensional Electrophoretic “Mapping” of Human Platelet Membrane Proteins
Authors: Nichols W. L. , Mann K. G. 
Published: May 2019

Two-dimensional electrophoresis of solubilized human platelet membrane proteins utilizing Polyacrylamide gel isoelectric focusing followed by sodium dodecyl sulfate (SDS) slab gel electrophoresis with discontinuous buffer systems yields a high resolution “fingerprint” of platelet membrane proteins. Membranes were prepared from citrate-phosphate-dextrose (CPD) platelet concentrates by differential centrifugation, repeated washes and lysis by means of sonication or glycerol hypotonic lysis. Membrane vesicles were isolated on step gradients of 27%(w/v) or 30% (w/w) sucrose. Following further washing of the vesicles, membrane pellets were extracted by heating in SDS and β-mercaptoethanol. After pelleting the insoluble material, the resulting supernatant was found to contain most of the total protein content of the membrane, and to yield SDS gel patterns similar to platelet membranes totally solubilized with larger amounts of SDS. Extracts were dialyzed against 9M urea, 2% Triton X-100 at 37° for 12 hrs., then electrofocused in large-pore gels containing 9M urea, 1% Triton X-100 and 1.6% to 2.0% ampholyte (pH 3–10). Electrofocused samples were equilibrated with 1% SDS in half-strength stacking gel buffer (D. M. Neville, J. Biol. Chem. 246: 6328, 1971)and electrophoresed in the second dimension into slab gels.Coomassie Blue R-250 staining revealed more than 40 components, the majority of which electro-focused between pH 4.5 – 7. The major glycoproteins, as assessed by periodic acid-Schiff staining, electrofocus at acidic pH. The greater resolution obtained by this analytical technique will be useful in the further characterization of the membrane proteins of normal and abnormal platelets.
Soluble Fibrin Complexes During Hormonal Contraception
Authors: Asbeck F. , Bebber J. , van de Loo J. 
Published: May 2019

In a prospective study, 2o healthy women (16–35 yrs.) were treated with an oral contraceptive (o,25 mg D-norgestrel, o,o5 mg ethinyl-estradiol). Derivatives of fibrinogen and fibrin were investigated before the beginning of medication, after the 1st cycle, and after the 3rd cycle. The investigations included: determination of thrombin-clottable protein, cold precipitable protein (4°C) , ethanol precipitable protein (11,5%), ethanol gelation test, protamin sulfate test, fibrin-fibrinogen degradation products in serum, and quantitation of high-and low molecular weight derivatives of fibrinogen and fibrin by agarose gel filtration of the fresh patient plasmas.There was a significant increase of thrombin clottable protein (212 vs. 236 mg/dl, p<0,001) and an increase of ethanol precipitable protein (117 vs. 168 mg/dl, p<0,003). There was no change in the cold precipitable protein nor in the paracoagulation phenomena. Fibrin-fibrinogen degradation products were not elevated. By agarose gel filtration, a significant increase in soluble fibrin complexes (p<0,02) could be demonstrated; the highest concentration of the SFC elu-ted in the position of the dimers.The study confirms a low grade activation of the coagulation system even in healthy women taking a low dose estrogen containing oral contraceptive.
Behaviour of Soluble DES-AB Fibrin and Fibrinogen in Man
Authors: Mahn I. , Müller-Berghaus G. 
Published: May 2019

Human des-AB fibrin was generated from I-131-fibrinogen by clotting with thrombin in the presence of EDTA and aprotinin, and solubilized in buffered urea. About 1 to 2 mg of fibrin was injected simultaneously with I-125-fibrinogen dissolved in buffered urea into 14 male healthy volunteers.The mean distribution volume of the soluble fibrin was 48.5 ml/kg in comparison to 46.1 ml/kg of the injected fibrinogen demonstrating a homogeneous distribution of both the labelled proteins in the circulating blood. The elimination characteristics of the soluble fibrin did not represent a monophasic exponential decay. 24 hours after injection a mean of 24.3 % of the initial value of the fibrin was traced in the blood in comparison to a mean of 53.3 % of the fibrinogen at that time. The terminal slope of the fibrin elimination curve between 2 and 8 days after injection was a monophasic exponential curve with a mean T 1/2 of 2.3 days. The fibrinogen elimination curve showed a T 1/2 of 4.2 days during that period of time.These experiments indicate that solubilized fibrin injected into man can be traced in the circulating blood for a long period of time. The catabolic behaviour of fibrin differs significantly from that of fibrinogen.
Binding of Calcium to Fibrinogen: Some Related Properties
Authors: Marguerie G. 
Published: May 2019

The calcium binding properties of bovin fibrinogen have been studied using equilibrium dialysis method. At pH 7.5 fibrinogen has 3 specific calcium binding sites of high affinity and several non specific binding sites of low affinity. Direct titration of the calcium induced proton release indicates that the binding center is a chelate. Thermal an acid denaturation is found to be markedly influenced by the presence of Ca++, suggesting that structural features are related to the binding. However the circular dichroism spectra show that no generalized conformational change is induced when Ca++ is bound to the protein.The plasminic digestion of fibrinogen is also found to be specificaly influenced by Ca++. The velocity of the initial cleavages is slightly reduced in the presence of calcium. It is therefore suggested that the C-terminal part of the Aα chain is involved in the binding.Considering the dimeric structure of the fibrinogen molecule, the presence of only 3 calcium binding sites of high affinity suggests the existence of “salt bridges” between the constitutive polypeptide chains.
Disorders of Fibrinogen and Factor XIII - Introduction
Authors: Nossel H.L. 
Published: May 2019

Transformations of the fibrinogen molecule are amongst the best biochemically defined reactions of the hemostatic mechanism. The exact peptide bonds cleaved by thrombin are known and the initial sites of plasmin attack are defined. The gamma chain cross-links produced by Factor XIIIa are characterized, and work is proceeding on the identification of the alpha-chain cross-links.Physiologically fibrinogen participates in a number of platelet functions including adhesion to collagen and foreign surfaces and ADP-induced aggregation. Polymerizing fibrin aggregates platelets. Fibrinogen not only acts as a substrate for thrombin but is a powerful reversible inhibitor of thrombin activity.Congenitally abnormal fibrinogen may be associated with a thrombotic tendency, a hemorrhagic tendency or be asymptomatic. Acquired molecular changes occur in thromboembolic disease, intravascular coagulation and possibly in liver disease. Assays for molecular alteration find increasing clinical application. In the present session the following topics will be dicussed:1. Relationship between fibrinogen and platelets2. Fibrin polymerization - biochemistry- physiological and clinical significance3. Cross-linking - biochemistry- physiological and clinical significance