bluuebunny/crossref_metadata_2025 huggingface dataset:
Coagulation Changes Induced by Endotoxin and Purified Contact Activation Product
Authors: Barth P , Zimmermann R
Published: June 2018

By use of purified contact activation product (CAP) it was possible to show that activation of the contact phase of the coagulation system can lead to a state of hypo-coagulability very similar to that occurring in the experimental Sanarelli-Shwartz-man phenomenon (SSP). The coagulation changes which occurred suggested that the difference between the effects of CAP administration and the typical experimental SSP appeared to be merely quantitative in nature. However, the fact that in our experiments on the classical SSP no stasis thrombi developed as the most significant sign of increased coagulation activity, may suggest that pathogenetically important differences exist.
Immunological Studies on the Blood Coagulation Factor X and Its Warfarin-induced Precursor
Authors: Gaudernack Gustav , Gladhaug Berre Åse , Østerud Bjarne , Prydz Hans
Published: June 2018

Monospecific antisera against the human coagulation factor X have been raised in rabbits by injections of purified antigen. Such antiserum was used to study the cross-reacting material without factor X activity which is present in the blood of warfarin-treated patients and animals as well as to study the changes in factor X during coagulation. One patient with congenital factor X deficiency was also studied.

A complete identity was found between factor X in Macaca mulatta and human blood. During warfarin treatment antigenically cross-reacting material appeared in plasma. This was not adsorbed on BaSO4, and inhibited the coagulation activity of normal factor X.

Both this material, normal factor X and the cross-reacting material in plasma from a patient congenitally deficient in factor X gave rise to split products during coagulation by the intrinsic pathway, i. e. all of them served as substrates for the intrinsic activator of factor X.
Thrombolysis with Streptokinase in Rabbits Dose Response, Fibrin-clot Specificity and Laboratory Evaluation of Fibrinolytic Effect
Authors: Nowak Andrzej , Gurewich Victor
Published: June 2018

An animal model was used in which venous thromboemboli of reproducible size could be formed. The effects of SK 500–50,000 units per hour were evaluated and compared to those of saline. Proportionately the greatest clot lysis occurred with the lowest doses of SK. In contrast to thrombolysis, significant fibrinogenolysis did not occur in any of the animals indicating a high degree of specificity of SK-induced activator for rabbit fibrin. An excellent correlation between the concentration of fibrin degradation products (fdp) measured by the serial dilution protamine sulfate test and the extent of clot lysis was found suggesting this to be a useful method for monitoring the effects of thrombolytic therapy. A method for the laboratory distinction of fdp from fibrin monomer was demonstrated.
Fibrinolysis and the Stomach: Biochemical Identification of the “Plasmin-like” Enzyme
Authors: Thomson J. M
Published: June 2018

The ‘plasmin-like’ enzyme previously demonstrated in gastric vein blood is studied further in a series of experiments using gel filtration chromatography. By comparison with purified enzymes it is identified as plasmin. Its non-identity to trypsin is also established. The ‘plasmin-like’ activity previously demonstrated in the peripheral blood, following gastric compression at laparotomy, is also studied in a similar way and shows the same characteristics. These results confirm the view that plasmin present in the peripheral veins of these patients has been released from the stomach.
A Comparative Study of Human and Monkey (Macaca irus) Fibrinogen Degradation Products
Authors: Poskitt Thomas R , Philip Fortwengler H , Roth Gerald J , Eaton James A
Published: June 2018

Immunochemical, physical, and anticoagulant properties of human and monkey (Macaca irus) fibrinogen degradation products (FDP’s) were compared by Immunoelectrophoresis, Sephadex G-200 gel filtration, and anticoagulant assay. Both species demonstrated a high degree of similarity in the properties and sequence of generation of FDP’s derived from in vitro plasmin digestion of highly purified fibrinogen. The results of this study should permit a closer analogy to be drawn between the pathogenic mechanisms of disseminated intravascular coagulation occurring experimentally in monkeys and clinically in humans.
Studies on the Characterization of Factor VIII and a Co-factor VIII
Authors: Paulssen M. M. P , Vandenbussche-Scheffers H. L. M. A , Spaan P. B , de Jong T , Planje M. C
Published: June 2018

Factor VIII occurs in the body in two different forms. In lymph factor VIII is bound to chylomicra. In plasma, factor VIII is bound to a protein.

After delipidation of chylomicra we obtained a glycoprotein with a high polysaccharide content and a molecular weight of approx. 160,000.

In plasma, factor VIII is attached to a protein which is present in normal concentrations in plasma of patients with haemophilia A and in serum (co-factor VIII).

This factor is deficient in both the plasma and the serum of patients with von Willebrand’s disease.

The binding between factor VIII and co-factor VIII is reversible.

Some properties of these two factors are described.
The Natural Course of Defibrination Syndrome Caused by Echis Colorata Venom in Man
Authors: Fainaru M , Eisenberg S , Manny N , Hershko C
Published: June 2018

The natural course of defibrination syndrome caused by Echis colorata venom (ECV) in five patients is reported. All patients developed afibrinogenemia within six hours after the bite. Concomitantly a depression in factor V was recorded. Factor VIII and thrombocyte count in blood were normal in most patients. In the light of the known effects of ECV on blood coagulation in vivo and in vitro it is concluded that the afibrinogenemia is due to intravascular clotting.

Four patients had transient renal damage, manifested by oliguria, azotemia, albuminuria and cylindruria, ascribed to microthrombi in the renal glomeruli.

After the bite, the natural course was benign, no major bleeding was observed, and all signs of coagulopathy reverted to normal within 7 days. Therefore we recommend no specific treatment for this condition. In the case of heavily bleeding patients, administration of antiserum against ECV and/or heparin should be considered.
The Rivanol Method for the Quantitative Determination of Antithrombin III in Plasma
Authors: Yue Robert H. , Starr Toby , Gertler Menard M.
Published: June 2018

A simple quantitative method for the determination of antithrombin III in plasma is described. It is based on the preferential precipitation of plasma antithrombin activities by a chemical compound 2,5-diamino-7-ethoxyacridin lactate (rivanol). When the incubation time of plasma with rivanol took place within 0.5 and 2 hours under specifically controlled experimental conditions, rivanol precipitated α2-macro-globulin selectively and quantitatively without any effect on antithrombin III. In the presence of rivanol, the inhibition of thrombin by plasma antithrombin III followed a second-order reaction with a rate constant of 80 1/M/sec. In this assay procedure, only the initial thrombin activity and the 30 minutes residual thrombin activity are required to evaluate the amount of antithrombin III present in the plasma quantitatively. “With proper routine laboratory care, this assay system was found to be accurate and reproducible.
Measurement of the Rate of Clot Retraction
Authors: Itoh Michio , Nishimura Yoshihisa , Takenaka Osamu , Inada Yuji
Published: June 2018

The volume of serum exuded from clot was measured with time in the presence of platelets. The change of the volume of clot followed the first order kinetics with respect to time and the rate constant (k) was introduced to assay for clot retraction. The value of k and maximal serum volume exuded from clot, Vf, are dependent on the number of platelets, but the way k depends on the number of platelets is different from that Vf does on it. This suggests that these two parameters reflect the different phases of clot retraction.
Modification of Platelet Sulfhydryl Groups
Authors: Harbury C. B , Schrier S. L
Published: June 2018

Sulfhydryl (SH) reagents are known to inhibit platelet aggregation but their effect on the release reaction has not been systematically studied. To delineate the functional effect of penetrating versus nonpenetrating SH inhibitors, we studied primary and secondary aggregation, the collagen and thrombin induced release reaction and clot retraction. Washed human platelets were used to avoid exposing plasma proteins and added reagents to SH inhibitors. We found that 5,5´ dithiobis (2 nitrobenzoic acid) interacted only with superficially-located SH groups which were not essential for either aggregation, the release reaction, clot retraction, or membrane stability. N-ethylmaleimide at low concentrations was found to interact in rapid succession with SH groups essential for aggregation, clot retraction, and the release reaction. Finally, at very much larger concentration, it may have interacted with a structural SH group. P-hydroxymercuriphenyl sulfonate presented a very complex pattern. At low concentrations it appeared to interfere with the free access to the platelet surface of externally-added agents. At higher concentrations, it interacted first with SH groups associated with aggregation, and then with SH groups associated with clot retraction. Finally, it appeared to interfere with structural SH groups, producing a membrane leak of proteins and nucleotides. The release reaction was never specifically inhibited.
The so-called “Onion-Like Shape Thromboelastogram” in Dialyzed Uraemic Patients
Authors: Suchecki Tadeusz
Published: June 2018

The behaviour of the so-called “onion-like shape thromboelastogram” in dialyzed uraemic patients has been studied. 51 double thromboelastogram (TEG) determinations (one before and one after dialysis) were performed in 39 uraemic patients. The “onion-Mke shape TEG” was present in 42 recordings performed before dialysis and only in 19 recordings after a single dialysis. The disappearance of the “onion-like shape TEG” can be interpreted as a normalising effect of the dialysis on the clot elasticity in a large percentage of uraemic patients.
On the Mechanism by which Cell Contact Induces the Release Reaction of Blood Platelets; the Effect of Cationic Polymers
Authors: Massini P , Lüscher E. F
Published: June 2018

Human blood platelets are aggregated by the basic polymers polylysine and DEAE- dextran. Under certain conditions a second phase of aggregation, concomitant with the release reaction, is elicited. The presence of ADP, calcium ions and a plasmatic cofactor within the primary aggregates are necessary for the induction of the release reaction. These experiments demonstrate that cell contact per se does not lead to a release reaction ; in order to become effective it must take place in the presence of ADP.
Zur Frage der kontinuierlichen unsichtbaren Blutgerinnung und Fibrinolyse in normalen und pathologischen Zuständen
Authors: Oyvin I. A , Islamov I. I
Published: June 2018

Versuche an Hunden haben gezeigt, daß die lange dauernde Anwendung der EAK in fibrinolysehemmenden Dosen keinen Einfluß auf die Geschwindigkeit der Wasser - und Eiweißfiltration durch Gefäßwände nach akutem Blutverlust oder bei Entwicklung eines akuten Lungenödems hat. Diese Ergebnisse sprachen gegen die Ansicht, daß an der inneren Oberfläche des Endothels und der Basalmembran der Gefäße ständig eine Fibrinschicht gebildet und durch Fibrinolyse wieder aufgelöst wird. Im Ruhezustand sind Gerinnungs- und Fibrinolysesysteme inaktiv. Es konnte der Verlauf einer unsichtbaren generalisierten Blutgerinnung und Fibrinolyse sowohl in der Zirkulation als auch an normalen Endothel- und Basalmembranoberflächen nicht bestätigt werden.
Relative Serum Antiplasmin Levels in Normal and Hemophilic Dogs Treated with Choline
Authors: McDonald D , Jackson Blanche , Boudreaux H. B , Myers R. B
Published: June 2018

Peroral administration of choline in relatively high dosage (300 or 600 mg choline dihydrogen citrate per 17-20 lb body weight, 4 times daily) caused no significant change in serum antiplasmin activity of either normal or factor VIII-deficient beagle dogs. Also, no alteration in antiplasmin level was found to be associated with the hemophilic state.

Canine serum antiplasmins are stable at low temperatures. Like human antiplasmins, they appear to have two major components which differ conspicuously in stability at 60° C.

Other data presented in this paper show that crude plasmin readily obtained from human serum euglobulins provides an enzyme preparation suitable for screening antiplasmin levels of sera by the caseinolytic method.
Messung der Plättchenadhäsivität mit einer modifizierten Form der Hellem II-Methodik unter besonderer Berücksichtigung des von Willebrand-Jürgens-Syndroms
Authors: Niessner H
Published: June 2018

Es wurde über eine Modifikation der von Hellem angegebenen, mit nicht antikoa-guliertem Vollblut arbeitenden Glaskugelfiltermethodik zur Messung der Plättchen-adhäsivität berichtet. Während die Normal werte höher lagen und auch eine geringere Streuung zeigten als im Hellenischen Verfahren, waren die bei Patienten mit von WillebrandJürgens-Syndrom gefundenen Ergebnisse über einen wesentlich größeren Meßbereich verteilt, ohne daß es jedoch zu einer Überlappung der bei Willebrandscher Erkrankung gemessenen Werte mit dem Normalbereich kam. Durch Steigerung der Flußgeschwindigkeit im Glaskugelfilter von 6,6 auf 11,2 ml/min sanken die Adhäsivi-tätswerte bei Willebrandscher Erkrankung weiter hoch signifikant ab. Die mit 11,2 ml/ min gefundenen Ergebnisse waren signifikant zum Faktor-VIII-Spiegel korreliert. Die Familienuntersuchungen ergaben innerhalb der einzelnen Familien einen stark wechselnden Schweregrad der Adhäsivitätsverminderung bei Mitgliedern mit manifestem von Willebrand-Jürgens-Syndrom. Außerdem war die Adhäsivität bei einer Angehörigen ohne klinische Symptomatik erniedrigt. Durch die Gabe von Kryopräzipitat bei Patienten mit von Willebrand-Jürgens-Syndrom konnten nur die verlängerte Blutungszeit und der erniedrigte Faktor-VIII-Spiegel, nicht jedoch die Adhäsivität korrigiert werden. Außer bei der Willebrandschen Erkrankung war die mit der modifizierten Hellem II-Technik gemessene Adhäsivität noch bei 2 Patienten mit kongenitaler Afibrinogenämie sowie 2 Patientinnen mit Thrombasthenie vermindert, wobei sich bei der Mutter der einen Patientin mit Thrombasthenie bei fehlender klinischer Symptomatik ebenfalls eine herabgesetzte Adhäsivität fand. Die verminderte Adhäsivität bei erhöhter Thrombozytenzahl wurde auf methodische Ursachen zurückgeführt. Eine weitere Gruppe mit verminderter Adhäsivität, gemessen mit der modifizierten Hellem II-Technik, waren urämische Patienten, wobei die Adhäsivitäts-werte signifikant zu den Serumkreatininspiegeln korreliert waren. Durch Steigerung der Flußgeschwindigkeit im Glaskugelfilter von 6,6 auf 11,2 ml/min konnte keine signifikante weitere Abnahme der Adhäsivitätswerte erzielt werden. Die gefundenen Ergebnisse wurden eingehend diskutiert.
Antihemophilic Factor: Separation of an Active Fragment Following Dissociation by Salts or Detergents
Authors: Owen W. G , Wagner Robert H.
Published: June 2018

Dissociation of canine antihemophilic factor (factor VIII, molecular weight >2 × 106) by salts and detergents was studied with the use of agarose gel chromatography. The dissociated fragments retained antihemophilic factor activity. Partial dissociation occurred in 1 M or 2 M KCl, 1 M KBr, 0.25% sodium desoxycholate and 0.1% Triton X-100, but essentially no dissociation was observed in 3 M KC1. A high degree of dissociation occurred in 0.25 M CaCl2. Removal of Ca2+ before chromatographic fractionation of the preparation resulted in complete reversal of the dissociation. However, upon separation of an active, dissociated fraction from the very high molecular weight components by gel chromatography in 0.25 M CaCl2, followed by removal of Ca2+ from the fraction, no tendency toward reaggregation was seen. The apparent molecular weight of the dissociated fragment, determined by gel chromatography, is about 25,000. It is proposed that antihemophilic factor activity is associated with a molecule, of relatively low molecular weight, which in plasma or partially purified fractions is bound by electrostatic and hydrophobic bonds to a high molecular weight carrier. The activities of both dissociated and undissociated preparations were neutralized by an antibody to human antihemophilic factor. In contrast to the behavior of undissociated antihemophilic factor, the activity of the dissociated preparation was not affected by incubation with a dilute, highly purified thrombin preparation.
Direction-dependent stretchability of AgNW electrodes on microprism-mediated elastomeric substrates
Authors: Justin Jesuraj P. , Shi Chuanqian , Kim Dong Hyun , Hafeez Hassan , Lee Jong Chan , Lee Won Ho , Choi Dae Keun , Zou Zhanan , Xiao Jianliang , Min Jeongho , Song Myungkwan , Kim Chang Su , Ryu Seung Yoon
Published: June 2018

Silver nanowires (AgNWs) have become an efficient electrode candidate for stretchable electronics. We report the effects of directional stretching in microprism-mediated AgNW stretchable electrodes on polyurethane (PU) substrates. The wavy substrate is fabricated using a customized microprism on polyethylene terephthalate. AgNWs on stretchable PU substrates show stable normalized resistance up to 35% strain under parallel uniaxial stretching. This performance is much better than AgNWs on bare PU substrate or on wavy PU under perpendicular stretching, which can only sustain 10%-15% strain before significant increase in normalized resistance. Finite element simulations were conducted to reveal the strain distribution and variation in the AgNW electrodes on both bare and wavy PU substrates when stretched along parallel and perpendicular directions. Comparing to AgNW electrodes on bare PU and on wavy PU under perpendicular stretching, the wavy PU surface relief features can effectively alleviate the strain in the AgNW network when stretched along parallel direction, leading to better performance.
Charge transfer dynamical processes at graphene-transition metal oxides/electrolyte interface for energy storage: Insights from in-situ Raman spectroelectrochemistry
Authors: Gupta S. , Carrizosa S. B. , Jasinski J. , Dimakis N.
Published: June 2018

Hybrids consisting of supercapacitive functionalized graphene (graphene oxide; GO reduced graphene oxide; rGO multilayer graphene; MLG, electrochemically reduced GO; ErGO) and three-dimensional graphene scaffold (rGOHT; hydrothermally prepared) decorated with cobalt nanoparticles (CoNP), nanostructured cobalt (CoO and Co3O4) and manganese (MnO2) oxide polymorphs, assembled electrochemically facilitate chemically bridged interfaces with tunable properties. Since Raman spectroscopy can capture variations in structural and chemical bonding, Raman spectro-electrochemistry in operando i.e. under electrochemical environment with applied bias is employed to 1) probe graphene/metal bonding and dynamic processes, 2) monitor the spectral changes with successive redox interfacial reactions, and 3) quantify the associated parameters including type and fraction of charge transfer. The transverse optical (TO) and longitudinal optical (LO) phonons above 500 cm−1 belonging to Co3O4, CoO, MnO2 and carbon-carbon bonding occurring at 1340 cm-1, 1590 cm−1 and 2670 cm-1 belonging to D, G, and 2D bands, respectively, are analyzed with applied potential. Consistent variation in Raman band position and intensity ratio reveal structural modification, combined charge transfer due to localized orbital re-hybridization and mechanical strain, all resulting in finely tuned electronic properties. Moreover, the heterogeneous basal and edge plane sites of graphene nanosheets in conjunction with transition metal oxide ‘hybrids’ reinforce efficient surface/interfacial electron transfer and available electronic density of states near Fermi level for enhanced performance. We estimated the extent and nature (n− or p−) of charge transfer complemented with Density Functional Theory calculations affected by hydration and demonstrate the synergistic coupling between graphene nanosheets and nanoscale cobalt (and manganese) oxides for applied electrochemical applications.
Magnetoelectric metglas/bidomain y + 140°-cut lithium niobate composite for sensing fT magnetic fields
Authors: Turutin Andrei V. , Vidal João V. , Kubasov Ilya V. , Kislyuk Alexander M. , Malinkovich Mikhail D. , Parkhomenko Yuriy N. , Kobeleva Svetlana P. , Pakhomov Oleg V. , Kholkin Andrei L. , Sobolev Nikolai A.
Published: June 2018

We investigated the magnetoelectric properties of a new laminate composite material based on y + 140°-cut congruent lithium niobate piezoelectric plates with an antiparallel polarized “head-to-head” bidomain structure and metglas used as a magnetostrictive layer. A series of bidomain lithium niobate crystals were prepared by annealing under conditions of Li2O outdiffusion from LiNbO3 with a resultant growth of an inversion domain. The measured quasi-static magnetoelectric coupling coefficient achieved |αE31| = 1.9 V·(cm Oe)−1. At a bending resonance frequency of 6862 Hz, we found a giant |αE31| value up to 1704 V·(cm Oe)−1. Furthermore, the equivalent magnetic noise spectral density of the investigated composite material was only 92 fT/Hz1/2, a record value for such a low operation frequency. The magnetic-field detection limit of the laminated composite was found to be as low as 200 fT in direct measurements without any additional shielding from external noises.
Distribution shapes govern the discovery of predictive models for gene regulation
Authors: Munsky Brian , Li Guoliang , Fox Zachary R. , Shepherd Douglas P. , Neuert Gregor
Published: June 2018

Significance

Systems biology seeks to combine experiments with computation to predict biological behaviors. However, despite tremendous data and knowledge, biological models make less-accurate predictions compared with other fields. By analyzing single-cell, single-molecule measurements of mRNA during yeast stress response, we explore why and how the shapes of experimental distributions control prediction accuracy. We show how asymmetric data distributions with long tails cause standard modeling approaches to yield excellent fits but make meaningless predictions. We show how these biases arise from the violation of fundamental assumptions in standard modeling approaches. We demonstrate how advanced computational tools solve this dilemma and achieve predictive understanding of spatiotemporal mechanisms of transcription control including RNA polymerase initiation and elongation and mRNA accumulation, transport, and decay.
Experiencing religious pilgrimage in Malta.
Authors: Zammit V.
Published: June 2018

This chapter discusses the Catholic pilgrimages on Malta in the context of social and sustainable development. After reviewing the history of some of the medieval pilgrimage trails on Malta, attention is then turned to discussing the more modern pilgrimages that take place on the island. Some of the socio-environmental issues that have arisen due to the use of these pilgrimages in tourism promotional literature are discussed.
Pilgrimage to Mount Bromo, Indonesia.
Authors: Choe JaeYeon Choe JaeYeon , Hitchcock M.
Published: June 2018

This chapter examines the pilgrimage tradition of the Tenggerese people, a Javanese ethnic group in Eastern Java, who travel to Mount Bromo during their celebration of the Yadnya Kasada or Kosodo festival to make offerings to the mountain gods. After looking at tourism to the island of Java more generally, the chapter discusses the history of this pilgrimage and looks at the significance of this pilgrimage for both the Tenggerese people and tourism officials and marketers, who have used this pilgrimage to promote religious tourism to the area. Attention is then turned to looking at the problems that have arisen because of the commodification of this pilgrimage ritual, before concluding with some recommendations for overcoming these issues.
The Shikoku pilgrimage: popularity and the pilgrim's transaction.
Authors: Wilkinson G.
Published: June 2018

This chapter uses the Shikoku pilgrimage in Japan to describe and analyse the importance of pilgrimage transactions for pilgrimage development. It is argued that pilgrims' transactions are central to the heritage identity and management of successful modern pilgrimage, as well as significant for regional economic growth. The Shikoku pilgrimage's history and the typical Japanese pilgrimage transactions are described to provide the necessary background for the chapter's arguments.
Challenges facing the sustainable development of slave trade routes and trails in Cameroon.
Authors: Enongene V. , Griffin K.
Published: June 2018

This chapter explores the recent growth of African American diaspora tourism as quasi-religious pilgrimage to the village of Bimbia, Cameroon, which served as a major slave port in the region. Having first discussed the historical development of slavery and slave trade routes in this region, the chapter discusses the recent development of the village of Bimbia in the context of slave routes, and the resultant 'pilgrimages of reconnection' to this area. In particular, the chapter focuses on the economic and environmental challenges related to the creation of slave routes that cater for 'slave pilgrims'.
The path to developing a one welfare framework.
Authors: Pinillos R. G.
Published: June 2018

The content of this book chapter combines the result of personal ideas from the author and collaborating experts, stakeholder discussion outputs, published literature, participants to an electronic global consultation on a One Welfare framework and definition proposal. One Welfare is a framework for improving animal welfare and human well-being. One Welfare developed in this book frames the many connections between humans, animals and the environment, and how harnessing this thinking will improve animal welfare. Improvements in animal welfare do not always progress as expected and most of the time it is humans who cause the majority of animal welfare issues. It is therefore necessary to ensure that human welfare aspects are considered if we are to achieve effective animal welfare improvements. Many agreed that One Welfare is a concept that encompasses, in a multidimensional way, a number of areas, including: the problems of animal production, workers and the impact on the environment of livestock farms; the reduction of violence across the world; and the connection between poor animal and human welfare states and how improved animal welfare can help improve human welfare. This book chapter aims to assist readers in identifying these connections and to inspire them to continue building up the evidence base in this area by putting One Welfare into practice and documenting further examples of these connections.
On biotechnology and animal welfare.
Authors: Rollin B. E.
Published: June 2018

In the course of human history, the primary use of animals for more than 10 000 years has been agricultural - food, fibre, locomotion and power. And for most of that history, the well-being of the animals being used was assured by necessity. If one did not practice good husbandry, the animals did not produce, and those who raised the animals were equally harmed. Proper treatment of animals therefore was presuppositional to civilization. Unfortunately, with the coming of the Industrial Revolution, humans abandoned the 'ancient contract' with animals that had lasted 10 000 years. We could now increase the productivity of animals by use of 'technological sanders' that allowed us to keep animals under conditions where their welfare suffered but they continued to produce. The advent of biotechnology showed that this same exploitative mindset would dominate agricultural biotechnology. The rise of animal experimentation similarly demonstrated cavalier human disregard for animal well-being. Rationalizations such as the Cartesian claim that animals were machines buttressed this disregard. As was the case with agriculture, biotechnological manipulation of animals again disregarded animal welfare. For these reasons, it is morally necessary to set strict sense standards for genetic manipulation. Furthermore, public support for animal research is inversely proportional to the animals' degree of suffering. Thus, ethics and self-interest converge in this case.
pyTFA and matTFA: a Python package and a Matlab toolbox for Thermodynamics-based Flux Analysis
Authors: Salvy Pierre , Fengos Georgios , Ataman Meric , Pathier Thomas , Soh Keng C , Hatzimanikatis Vassily
Published: June 2018

pyTFA and matTFA are the first published implementations of the original TFA paper. Specifically, they include explicit formulation of Gibbs energies and metabolite concentrations, which enables straightforward integration of metabolite concentration measurements.

Motivation

High-throughput analytic technologies provide a wealth of omics data that can be used to perform thorough analyses for a multitude of studies in the areas of Systems Biology and Biotechnology. Nevertheless, most studies are still limited to constraint-based Flux Balance Analyses (FBA), neglecting an important physicochemical constraint: thermodynamics. Thermodynamics-based Flux Analysis (TFA) in metabolic models enables the integration of quantitative metabolomics data to study their effects on the net-flux directionality of reactions in the network. In addition, it allows us to estimate how far each reaction operates from thermodynamic equilibrium, which provides critical information for guiding metabolic engineering decisions.

Results

We present a Python package (pyTFA) and a Matlab toolbox (matTFA) that implement TFA. We show an example of application on both a reduced and a genome-scale model of E. coli., and demonstrate TFA and data integration through TFA reduce the feasible flux space with respect to FBA.

Availability and implementation

Documented implementation of TFA framework both in Python (pyTFA) and Matlab (matTFA) are available on www.github.com/EPFL-LCSB/.

Supplementary information

Supplementary data are available at Bioinformatics online.
ShinyCNV: a Shiny/R application to view and annotate DNA copy number variations
Authors: Gu Zhaohui , Mullighan Charles G
Published: June 2018

Motivation

Single nucleotide polymorphism (SNP) array is the most widely used platform to assess somatic copy number variations (CNVs) in cancer studies. Many SNP data-based CNV callers are available, however, the false positive rates from automated calling are commonly high, and reported breakpoints can be inaccurate. Manual review for each reported CNV by visualizing the SNP data is important, but is challenging for users lacking computational experience. To address this, we present a Shiny/R application ShinyCNV, an interactive graphical user interface to view and annotate CNVs.

Results

With this application, normalized SNP data, which includes log R ratio (LRR) and B allele frequency, can be plotted against the reported CNVs, and users can visually check the reliability of CNVs per se or adjust the incorrectly assigned breakpoints. Further, the interactive LRR spectrum panel within ShinyCNV can facilitate the process to identify commonly affected CNV regions from a group of samples, and to visually check if important focal gains/losses are missing from reported CNVs. ShinyCNV is designed to be intuitive for cancer researchers and can be easily installed for either personal use or deployed on servers to provide online service.

Availability and implementation

ShinyCNV and the tutorial are freely available from https://github.com/gzhmat/ShinyCNV.

Supplementary information

Supplementary data are available at Bioinformatics online.
A pseudo knockoff filter for correlated features
Authors: Chen Jiajie , Hou Anthony , Hou Thomas Y
Published: June 2018

In Barber & Candès (2015, Ann. Statist., 43, 2055–2085), the authors introduced a new variable selection procedure called the knockoff filter to control the false discovery rate (FDR) and proved that this method achieves exact FDR control. Inspired by the work by Barber & Candès (2015, Ann. Statist., 43, 2055–2085), we propose a pseudo knockoff filter that inherits some advantages of the original knockoff filter and has more flexibility in constructing its knockoff matrix. Moreover, we perform a number of numerical experiments that seem to suggest that the pseudo knockoff filter with the half Lasso statistic has FDR control and offers more power than the original knockoff filter with the Lasso Path or the half Lasso statistic for the numerical examples that we consider in this paper. Although we cannot establish rigourous FDR control for the pseudo knockoff filter, we provide some partial analysis of the pseudo knockoff filter with the half Lasso statistic and establish a uniform false discovery proportion bound and an expectation inequality.
Principal Submatrices, Restricted Invertibility, and a Quantitative Gauss–Lucas Theorem
Authors: Ravichandran Mohan
Published: June 2018

We apply the techniques developed by Marcus, Spielman, and Srivastava, working with principal submatrices in place of rank-$1$ decompositions to give an alternate proof of their results on restricted invertibility. This approach recovers results of theirs’ concerning the existence of well-conditioned column submatrices all the way up to the so-called modified stable rank. All constructions are algorithmic. The main novelty of this approach is that it leads to a new quantitative version of the classical Gauss–Lucas theorem on the critical points of complex polynomials. We show that for any degree $n$ polynomial $p$ and any $c \geq 1/2$, the area of the convex hull of the roots of $p^{(\lfloor cn \rfloor )}$ is at most $4(c-c^2)$ that of the area of the convex hull of the roots of $p$.
Rigidity of Nonnegatively Curved Surfaces Relative to a Curve
Authors: Ghomi Mohammad , Spruck Joel
Published: June 2018

We prove that any properly oriented $\mathcal{C}^{2,1}$ isometric immersion of a positively curved Riemannian surface $M$ into Euclidean 3-space is uniquely determined, up to a rigid motion, by its values on any curve segment in $M$. A generalization of this result to nonnegatively curved surfaces is presented as well under suitable conditions on their parabolic points. Thus, we obtain a local version of Cohn-Vossen’s rigidity theorem for convex surfaces subject to a Dirichlet condition. The proof employs in part Hormander’s unique continuation principle for elliptic partial differential equations. Our approach also yields a short proof of Cohn-Vossen’s theorem.
Selective Exposure Theories
Authors: Stroud Natalie Jomini
Published: June 2018

This chapter provides an overview of the theory of selective exposure, the idea that people purposefully select messages matching their beliefs. After reviewing several psychological explanations for why the phenomenon occurs, the chapter turns to describing various forms of selective exposure. Selective exposure can be studied in terms of whether people select news or entertainment, the issues about which people seek information, which medium is selected in obtaining information, and the extent to which like-minded information is preferred. Numerous moderators of the links between citizens’ beliefs and their information selection are presented. Next, the chapter details four different methodological techniques that have been used to study selective exposure. Finally, the chapter outlines a host of unanswered questions about selective exposure for future researchers to tackle.
Candidate Traits and Political Choice
Authors: Hardy Bruce W.
Published: June 2018

What role do presidential candidate character traits play in vote decisions? To some, the answer is obvious as campaigns, journalists, pundits, and voters frequently differentiate presidential candidates in terms of their personal qualities—traits are deemed important. On the other hand, past research suggests that, while candidate character traits are short term forces, they hold relatively limited in influence on vote preference. However, theoretical and methodological limitations may have hindered past research ability to detect the true influence of character traits in voter decisions. This author reviews past literature, offers a clear conceptualization of candidate character traits, presents ways in which trait may influence vote choice, and suggests areas for future research.
The Political Uses and Abuses of Civility and Incivility
Authors: Jamieson Kathleen Hall , Volinsky Allyson , Weitz Ilana , Kenski Kate
Published: June 2018

After exploring the challenges involved in defining incivility, this chapter addresses the evolution of the concept, notes the dispute over trend lines, and précises work on its psychological effects. It then outlines some functions that civility and incivility serve, such as the functions of differentiating and mobilizing, marginalizing the powerless, expressing, and deliberating. The use of calls for civility as a means of social control is discussed, and then the chapter flags questions worthy of additional attention.
Models and Methods of Assessing Adaptive Behavior
Authors: Hangauer Jason , Worcester Jonathan , Armstrong Kathleen Hague
Published: June 2018

This chapter will summarize contemporary models and methods used for the assessment of adaptive behavior functioning in children and adolescents. This chapter will also emphasize how to best use such assessment information for diagnostic and eligibility purposes and in developing interventions and support plans. We will review the use of traditional, norm-referenced adaptive behavior assessment tools as well as what will be referred to as “supplemental methods,” including the direct observation of adaptive skill functioning. The assessment of adaptive behavior with respect to developmental expectations, cultural expectations, systems of care, and legislation will also be discussed. Lastly, case studies will be presented to illustrate the usefulness of these methods in assessing individuals and planning effective interventions and services.
Christianity and Korean Traditional Music
Authors: Howard Keith David
Published: June 2018

Keith Howard offers an account of how Korean Christians who are professional musicians specializing in traditional music (kugak) have been attempting to construct a relationship between their faith and Korean traditional music, by incorporating Christian narratives into traditional musical forms, such as p’ansori. Howard notes that both Christianity and Korean traditional music constitute powerful symbols of the place of Korea (for Koreans) in the globalized world; however, because of the contradictory logics of two transnationally imagined identity politics—one imagining Korea as modern and privileging the Western, and the other focusing on Korean “heritage” and privileging the “Korean”—the institutional spaces of Korean traditional music and Christian music have remained separate and distinct.
Temperamental Contributions to Inhibited and Uninhibited Profiles
Authors: Kagan Jerome
Published: June 2018

A temperamental bias is currently defined as a behavioral profile with a partial origin in the child’s biology that varies among individuals. These biases, which appear early in development, are sculpted by experience into a variety of personality profiles. This chapter first describes possible genetic and nongenetic bases for temperamental categories, followed by a detailed presentation of the research on high- and low-reactive infants who are biased to become inhibited or uninhibited children. The chapter concludes with a discussion of the implications of these two temperaments to psychopathology and speculations on the temperamental variation among reproductively isolated human groups. A large number of questions remain unanswered. Perhaps the most critical is discovering the genes and resulting neurochemical or neuroanatomical features that contribute to the high- and low-reactive profiles.
Transcriptional signatures for coupled predictions of stage II and III colorectal cancer metastasis and fluorouracil‐based adjuvant chemotherapy benefit
Authors: Song Kai , Guo You , Wang Xianlong , Cai Hao , Zheng Weicheng , Li Na , Song Xuekun , Ao Lu , Guo Zheng , Zhao Wenyuan
Published: June 2018

The current study suggests that the identification of predictive signatures of fluorouracil (5‐FU) response for stage II and III colorectal cancer (CRC) could be confounded by chemotherapy‐irrelevant low relapse risk. Using the samples of patients with stage II and III CRC who were treated with curative surgery only, we identified a signature with which to predict chemotherapy‐irrelevant relapse risk for patients after curative surgery. By applying this signature to the samples of patients with stage II and III CRC who were treated with 5‐FU–based adjuvant chemotherapy (ACT) after surgery, we predicted the relapse risk if treated with surgery only. From high‐risk samples, we further identified another signature with which to predict therapeutic benefit from 5‐FU–based ACT. On the basis of the relative expression orderings of gene pairs, a postsurgery relapse risk signature that consisted of 44 gene pairs was developed and verified in 3 independent data sets. A 5‐FU therapeutic benefit signature that consisted of 4 gene pairs was then developed to predict the response of 5‐FU–based ACT for those patients with high relapse risk after curative surgery. The signature was verified in 4 independent datasets. For patients with stage II and III CRC, the coupled signatures can first identify patients with high relapse risk after curative surgery, then predict therapeutic benefit from 5‐FU–based ACT.—Song, K., Guo, Y., Wang, X., Cai, H., Zheng, W., Li, N., Song, X., Ao, L., Guo, Z., Zhao, W. Transcriptional signatures for coupled predictions of stage II and III colorectal cancer metastasis and fluorouracil‐based adjuvant chemotherapy benefit. FASEB J. 33, 151–162 (2019). www.fasebj.org
Diet‐induced β‐cell insulin resistance results in reversible loss of functional β‐cell mass
Authors: Paschen Meike , Moede Tilo , Valladolid-Acebes Ismael , Leibiger Barbara , Moruzzi Noah , Jacob Stefan , García-Prieto Concha F. , Brismar Kerstin , Leibiger Ingo B. , Berggren Per-Olof
Published: June 2018

Although convincing in genetic models, the relevance of β‐cell insulin resistance in diet‐induced type 2 diabetes (T2DM) remains unclear. Exemplified by diabetes‐prone, male, C57B1/6J mice being fed different combinations of Western‐style diet, we show that β‐cell insulin resistance occurs early during T2DM progression and is due to a combination of lipotoxicity and increased β‐cell workload. Within 8 wk of being fed a high‐fat, high‐sucrose diet, mice became obese, developed impaired insulin and glucose tolerances, and displayed noncompensatory insulin release, due, at least in part, to reduced expression of syntaxin‐1A. Through reporter islets transplanted to the anterior chamber of the eye, we demonstrated a concomitant loss of functional β‐cell mass. When mice were changed from diabetogenic diet to normal chow diet, the diabetes phenotype was reversed, suggesting a remarkable plasticity of functional β‐cell mass in the early phase of T2DM development. Our data reinforce the relevance of diet composition as an environmental factor determining different routes of diabetes progression in a given genetic background. Employing the in vivo reporter islet–monitoring approach will allow researchers to define key times in the dynamics of reversible loss of functional β‐cell mass and, thus, to investigate the underlying, molecular mechanisms involved in the progression toward T2DM manifestation.—Paschen, M., Moede, T., Valladolid‐Acebes, I., Leibiger, B., Moruzzi, N., Jacob, S., García‐Prieto, C. F., Brismar, K., Leibiger, I. B., Berggren, P.‐O. Diet‐induced β‐cell insulin resistance results in reversible loss of functional β‐cell mass. FASEB J. 33, 204–218 (2019). www.fasebj.org
Balloon Kyphoplasty Versus Conservative Treatment for Acute Osteoporotic Vertebral Fractures With Poor Prognostic Factors
Authors: Hoshino Masatoshi , Takahashi Shinji , Yasuda Hiroyuki , Terai Hidetomi , Watanabe Kyoei , Hayashi Kazunori , Tsujio Tadao , Kono Hiroshi , Suzuki Akinobu , Tamai Koji , Ohyama Shoichiro , Toyoda Hiromitsu , Dohzono Sho , Kanematsu Fumiaki , Hori Yusuke , Nakamura Hiroaki
Published: June 2018

Study Design.

A multicenter, prospective, single-arm, intervention study.

Objective.

The aim of this study was to investigate efficacy of balloon kyphoplasty (BKP) for acute osteoporotic vertebral fractures (OVFs) in patients with poor prognostic factors.

Summary of Background Data.

The indications for BKP remain unclear. Characteristic magnetic resonance imaging (MRI) findings (high-intensity or diffuse low-intensity area in fractured vertebrae on T2-weighted images) were reportedly predictive of delayed union.

Methods.

This study enrolled 106 patients with poor prognostic MRI findings who underwent BKP within 2 months after injury, and 116 controls with acute OVFs and the same poor prognostic factors who underwent conservative treatment. Patients were propensity score matched in a logistic regression model adjusted for age, sex, number of baseline old fractures, and fracture level. The primary outcome was reduction in activities of daily living (ADLs) at 6 months after fracture, and the secondary outcomes were improvement in short-form (SF)-36 subscales, back pain visual analog scale (VAS) score, and vertebral body deformity.

Results.

A decrease in ADLs occurred in 5.6% of patients in the BKP group and 25.6% of patients in the conservative treatment group (P < 0.001). The SF-36 vitality subscale score improved by 26.9 ± 25.9 points in the BKP group and 14.5 ± 29.4 points in the control group (P = 0.03). The VAS pain score improved by 43.4 ± 34.4 in the BKP group and 52.2 ± 29.8 in the control group (P = 0.44). The vertebral body wedge angle improved by 5.5 ± 6.2° in the BKP group and −6.3 ± 5.0° in the control group (P < 0.0001). The percent vertebral body height improved by 15.2 ± 19.2% in the BKP group and −20.6 ± 14.2% in the control group (P < 0.0001).

Conclusion.

ADLs, quality of life, and vertebral deformity showed greater improvement with BKP intervention for acute OVF with poor prognostic factors than with conservative treatment at 6 months after injury. Our treatment strategy uses BKP intervention according to the presence or absence of poor prognostic MRI findings.

Level of Evidence: 4