bluuebunny/crossref_metadata_2025 huggingface dataset:
Etude de l’activité antihéparinique des plaquettes par la méthode simple de Deutsch
Authors: Mayer G , Mayer S , Waitz R ,   avec l’assistance technique de Mme D. Jacob-Gerhard
Published: July 2018

L’activité antihéparinique des plaquettes est déterminée dans le test de Deutsch et exprimée en rendement antihéparinique ou quantité d’héparine neutralisée par 107 plaquettes.

Celui-cidépend de la concentration des plaquettes dont l’optimum est de 107 éléments, de la quantité présente d’héparine qui est optima pour 1/8- d’unité. Il ne peut dépasser une valeur maxima d’environ 1/40 d’unité d’héparine. Il est lié à l’état des plaquettes qui doivent être conservées individuellement tout en présentant les altérations décrites dans la métamorphose visqueuse à ses débuts.

Lerendement antihéparinique ne mesure donc pas la quantité de F. P. 4 libéré par la destruction des plaquettes mais traduit une réaction où F. P. 4 se trouve lié à un matériel qui limite son action sur l’héparine et de plus le rend fragile.

L’étude du rendement antihéparinique dans les cas pathologiques ne permet encore aucune conclusion si non que dans les affections plaquettaires le plus souvent il n’y a nul parallélisme entre le comportement du F. P. 3 et celui du F. P. 4.
Intravasale Thrombusbildung durch elektrischen Strom und Thrombolyse
Authors: Martin M , Staubesand J
Published: July 2018

1. Elektronenmikroskopische Befunde an Venenendothelien der Maus nach Einwirken von elektrischem Strom, der über eine Anode zugeführt wurde, ergaben eine schwere Zellschädigung bis zu völliger Zerstörung des Endothels. Das Endothel der kleinen Arterien reagierte abweichend mit Bildung großer Vakuolen, die sich gegen das Gefäßlumen vorwölbten, es weitgehend verlegten und damit eine Thrombolyse erschwerten oder sogar unmöglich machten.

2. Die Reaktion auf derartige Venenendothelschädigungen bestand von der Blutseite her in einer Aggregation von mehr oder weniger stark degranulierten Thrombozyten. Aggregierte Plättchen im Bereich des Gefäßlumens ohne Kontakt mit Endothel wurden nur selten beobachtet. Kam es zu einer so starken Stromschädigung, daß eine völlige Vernichtung des Endothels mit freier Kommunikation zwischen Blut und subendothelialem Bindegewebe die Folge war, wurde regelmäßig Fibrin in großen Mengen im Bereich der Gefäßwand abgeschieden.

3. Da Thrombozytenaggregation und Fibrinbildung nicht allein von der Stromeinwirkung, sondern im wesentlichen vom Grad der Endothelschädigung abhingen, und da in zusätzlichen In-vitro-Versuchen keine Abhängigkeit der Vollbhitgerinnung von der Zufuhr elektrischen Stroms nachgewiesen werden konnte, wird die Hypothese einer primär durch elektrostatische Vorgänge eingeleiteten Thromboseentstehung verworfen.

4. 24 h und 3 Tage nach Auflösung strominduzierter Thromben durch Streptokinase konnte Endothel als organisierter Bestandteil der Gefäßwand nicht mehr nachgewiesen werden. Die Funktion der Endothelzellen wurde in diesem Stadium von einer ein- bis mehrschichtigen Lage mäßig degranulierter Thrombozyten eingenommen, die untereinander durch Ausbildung von »regiones densae« und gegenseitige Verzahnung dem Blutstrom ein festes Widerlager boten. Die Bedeutung dieser bisher wenig beachteten Thrombozytenfunktion im Rahmen experimenteller Eingriffe an Blutgefäßen wird diskutiert.
Kinetic Studies of Platelet Aggregation Induced by Adenosine Diphosphate and Its Inhibition by Chelating Agents, Guanidino Compounds, and Adenosine
Authors: Skoza L , Zucker Marjorie B , Jerushalmy Z , Grant R
Published: July 2018

The kinetics, activation, pH dependence and inhibition of platelet aggregation induced by ADP were studied by recording the OD of stirred PRP from blood anticoagulated with acid-citrate-dextrose solution. There was a lag period between the addition of ADP and the initiation of aggregation. Addition of ADP in the absence of stirring or ionized calcium did not cause aggregation. When aggregation was subsequently initiated by stirring or the addition of CaCl2 there was no lag period. The steepest slope of the OD curve was used as the reaction velocity (V). It was affected by the concentration of calcium ions and was maximum at pH 8.0. When the ADP concentration was varied in the presence of different concentrations of ionized calcium, the overall kinetics revealed a series of rectangular hyperbola segments which did not pass through the origin. These observations led to the conclusion that the overall reaction can be depicted as a chain reaction: ADP interacts reversibly with platelets; when calcium is present these platelets become “sticky” and, when stirred, they aggregate. Kinetic studies of inhibition indicated that adenosine is a competitive inhibitor of ADP. The guanidino compounds tested were noncompetitive with respect to ADP but their inhibitory activity was counteracted by calcium.
Leukocytes and Thrombosis
Authors: Henry R. L
Published: July 2018

White blood cells can no longer be considered simple trapped inclusions within thrombi. Their numbers in thrombi relative to blood counts increase with time. They appear to come from the blood flowing past the thrombus. They appear to migrate by amoeboid movement into the thrombic mass. Polymorphonuclear neutrophils have been shown to be lytic to fibrin and other proteins and thus can contribute to thrombus dissolution. There is increasing evidence that neutrophils may impart important cytotrophic function to proliferating cells during thrombus organization. Eosinophils are known to carr profibrinolysin and will release this precursor at sites of fibrin deposition. Mononuclear leukocytes can transform into fibroblasts in tissue culture and I consider a thrombus an ideal tissue culture medium. All of these cells can contribute to thrombus dissolution simply by mechanical weakening of the mass by migration into it, releasing enzymes, and allowing blood flow to carry away pieces of the thrombus as emboli. I extend my perspective on thrombosis by considering these intravascular solids as cell tissue cultures rather than simple blood clots or platelet aggregates.
Fibrinolytische Aktivität von Handelsthrombinen und ihr Einfluß auf die Genauigkeit der Standard-fibrinplattenmethode
Authors: Schulte W
Published: July 2018

Handelsübliche Thrombinpräparate besitzen eine fabrikatabhängige und chargenabhängige fìbrinolytische Aktivität. Diese ist vorwiegend auf den Gehalt an Plasminogenaktivator- und -proaktivator zurückzuführen. Werden diese Präparate zur Herstellung von Standardfibrinplatten benutzt, so kann eine völlige Verfälschung der Testergebnisse resultieren, weil eine »Autolyse« der Platte eintritt. Versuche mit verschiedenen zur Plattenherstellung benutzten Thrombinpräparaten beweisen dies und zeigen außerdem, daß ein Zusatz von Akridin möglicherweise geeignet ist »stabilere« Standardfibrinplatten herzustellen.
Plasma physics of liquids—A focused review
Authors: Vanraes Patrick , Bogaerts Annemie
Published: July 2018

The interaction of plasma with liquids has led to various established industrial implementations as well as promising applications, including high-voltage switching, chemical analysis, nanomaterial synthesis, and plasma medicine. Along with these numerous accomplishments, the physics of plasma in liquid or in contact with a liquid surface has emerged as a bipartite research field, for which we introduce here the term “plasma physics of liquids.” Despite the intensive research investments during the recent decennia, this field is plagued by some controversies and gaps in knowledge, which might restrict further progress. The main difficulties in understanding revolve around the basic mechanisms of plasma initiation in the liquid phase and the electrical interactions at a plasma-liquid interface, which require an interdisciplinary approach. This review aims to provide the wide applied physics community with a general overview of the field, as well as the opportunities for interdisciplinary research on topics, such as nanobubbles and the floating water bridge, and involving the research domains of amorphous semiconductors, solid state physics, thermodynamics, material science, analytical chemistry, electrochemistry, and molecular dynamics simulations. In addition, we provoke awareness of experts in the field on yet underappreciated question marks. Accordingly, a strategy for future experimental and simulation work is proposed.
Electric power regulation and modeling of a central tower receiver power plant based on artificial neural network technique
Authors: Moukhtar Ibrahim , A. Elbaset Adel , Z. El Dein Adel , Qudaih Yaser , Blagin Evgeny , Uglanov Dmitry , Mitani Yasunori
Published: July 2018

This paper addresses an intelligent control scheme using the artificial neural network (ANN) technique for modeling and simulating a central tower receiver (CTR) plant with thermal energy storage (TES). The multilayer perceptron neural network (MLPNN) was implemented with two input parameters, one output parameter, and one hidden layer. The inputs comprise the receiver inlet temperature and the receiver thermal power. The output includes the mass flow rate of heat transfer fluid. A total of 888 datasets and three types of training algorithms, Levenberg-Marquardt (LM), Quasi-Newton, and Scaled Conjugate Gradient, are applied for training the proposed MLPNN model. Among all the investigated learning algorithms, the adopted LM with 40 neurons in the first hidden layer displayed superior ability to efficiently estimate the required performance compared to other learning algorithms. Based on the statistical evaluations, the optimized LM delivered preferred values for the root mean square error (0.0037), the coefficient of variance (0.0011), and the coefficient of determination (0.9999) during the training process. Hence, the MLPNN with LM-40 is an effective technique to precisely control the mass flow rate and subsequently the receiver outlet temperature regardless of the variations in the direct solar radiation and receiver inlet temperature. Furthermore, the generation strategy was modified to regulate CTR/TES output through electricity generation according to the hot storage system conditions. The performance of the adopted CTR-ANN model is presented and compared with the System Advisor Model (SAM) results. The results demonstrate better compatibility between the adopted CTR-ANN model and SAM outputs. The simplicity and minimum required input data of our proposed model make it appropriate for evaluating the power system reliability by using the Monte Carlo method.
Feral cat predation on Leadbeater’s possum (Gymobelideus leadbeateri) and observations of arboreal hunting at nest boxes
Authors: McComb Leo B. , Lentini Pia E. , Harley Dan K. P. , Lumsden Lindy F. , Antrobus Joanne S. , Eyre Arabella C. , Briscoe Natalie J.
Published: July 2018

Feral cats have been identified as a major threat to Australian wildlife; however, their impacts on the critically endangered Leadbeater’s possum (Gymobelideus leadbeateri) are unknown. Here, we describe camera trap observations of a feral cat hunting at nest boxes occupied by Leadbeater’s possum. Seven feral cats were subsequently captured within the surrounding area: two had Leadbeater’s possum remains in their stomachs. The prevalence of cat predation on this species, particularly at nest boxes, and how this can be mitigated warrants further investigation.
Siliquapyranone: A Tannic Acid Tetrahydropyran-2-one Isolated from the Leaves of Carob (Ceratonia siliqua) by Pressurised Hot Water Extraction
Authors: Deans Bianca J. , Skierka Brianna E. , Karagiannakis Benjamin W. , Vuong Daniel , Lacey Ernest , Smith Jason A. , Bissember Alex C.
Published: July 2018

Studies of the phytochemistry of carob (Ceratonia siliqua) leaf material are extremely limited. This report features the second natural product isolation study of carob leaves and the first such investigation of C. siliqua grown in Australia. Investigation of leaf material from seven carob cultivars using pressurised hot water extraction (PHWE) revealed the presence of high levels of myricitrin, d-pinitol, and sucrose in addition to the previously unreported natural product siliquapyranone {(2R,3R,4S,5R,6R)-5-hydroxy-6-(hydroxymethyl)-2-(((2S,4S)-2-methyl-6-oxotetrahydro-2H-pyran-4-yl)oxy)tetrahydro-2H-pyran-3,4-diyl bis(3,4,5-trihydroxybenzoate)}. Siliquapyranone represents a biosynthetic fusion of conventional 2,3-gallate esters on a β-glucose tannin with a hydroxytetrahydro-2H-pyran-2-one-related non-tannin tetrahydropyran-2-one, parasorboside. Preliminary biological testing indicates that siliquapyranone exhibits weak activity against both tumour and normal cell lines. This suggests that, like most tannins and parasorboside, siliquapyranone may act as an antifeedant.
Effects of interaction between montmorillonite and Sphingomonas sp. GY2B on the physical and chemical properties of montmorillonite in the clay-modulated biodegradation of phenanthrene
Authors: Ruan Bo , Wu Pingxiao , Wang Huimin , Li Liping , Yu Langfeng , Chen Liya , Lai Xiaolin , Zhu Nengwu , Dang Zhi , Lu Guining
Published: July 2018

Environmental contextInteractions between microbes and minerals can influence geochemical reactions, and hence are of fundamental importance in natural environmental processes. We investigate the effects of Sphingomonas sp. on the structure and physicochemical properties of montmorillonite, a common clay mineral, and determine how this interaction influences the biodegradation of phenanthrene. The findings have profound impact on the clay-modulated biodegradation of organic compounds in the environment.
AbstractWe investigate the effect of Sphingomonas sp. GY2B on the structure and physicochemical properties of montmorillonite (Mt). The simultaneous biodegradation of a polycyclic aromatic hydrocarbon compound, phenanthrene, was also monitored. After interaction with bacteria for 2 days, the increases of the specific surface area (SSA) and micropore volume, differences of the thermogravimetric analysis and differential scanning calorimetry (TGA-DSC) patterns and the morphological changes revealed modification of the physicochemical properties and mineral surface. Although the interlayer spacing of Mt remained unchanged, the appearance and shift of several vibration peaks in the Fourier transform infrared (FTIR) spectra confirmed the structural changes of Mt arising from bacterial activities. Concentrations of the major elements of montmorillonite changed greatly in the aqueous solution, especially Si, Al, Fe and Ca. Based on the analyses of X-ray diffraction (XRD) and FTIR, these changes were mainly ascribed to the formation of precipitates and minerals in the biotic experiment. Changes in the release rate of different elements also substantiated that the GY2B strain has a considerable impact on the dissolution of montmorillonite. Additionally, a preferential release of Si and the 27Al and 29Si cross-polarisation magic-angle spinning nuclear magnetic resonance (CP/MAS NMR) spectra of bacteria-untreated samples demonstrated that tetrahedral sheets were preferentially destroyed and octahedral sheets in montmorillonite were dissolved. These results showed that microorganisms can greatly affect the physical and chemical properties of clay minerals in the clay-modulated biodegradation of hydrophobic organic contaminants. This study provides valuable insight into the clay-modulated microbial remediation of organic pollutants in the environment.
Ecumenical alethic pluralism
Authors: Ferrari Filippo , Moruzzi Sebastiano
Published: July 2018

Ecumenical Alethic Pluralism (EAP) is a novel kind of alethic pluralism. It is ecumenical in that it widens the scope of alethic pluralism by allowing for a normatively deflated truth property alongside a variety of normatively robust truth properties. We establish EAP by showing how Wright’s Inflationary Arguments fail in the domain of taste, once a relativist treatment of the metaphysics and epistemology of that domain is endorsed. EAP is highly significant to current debates on the nature of truth insofar as it involves a reconfiguration of the dialectic between deflationists and pluralists.
Profiting from poverty
Authors: Koksvik Ole , Øverland Gerhard
Published: July 2018

We consider whether and under what conditions it is morally illicit to profit from poverty. We argue that when profit counterfactually depends on poverty, the agent making the profit is morally obliged to relinquish it. Finally, we argue that the people to whom the profit should be redirected are those on whom it counterfactually depends.
Tle corepressors are differentially partitioned to instruct CD8+ T cell lineage choice and identity
Authors: Xing Shaojun , Shao Peng , Li Fengyin , Zhao Xudong , Seo Wooseok , Wheat Justin C. , Ramasamy Selvi , Wang Jianfeng , Li Xiang , Peng Weiqun , Yu Shuyang , Liu Chengyu , Taniuchi Ichiro , Sweetser David A. , Xue Hai-Hui
Published: July 2018

Tle/Groucho proteins are transcriptional corepressors interacting with Tcf/Lef and Runx transcription factors, but their physiological roles in T cell development remain unknown. Conditional targeting of Tle1, Tle3 and Tle4 revealed gene dose–dependent requirements for Tle proteins in CD8+ lineage cells. Upon ablating all three Tle proteins, generation of CD8+ T cells was greatly diminished, largely owing to redirection of MHC-I–selected thymocytes to CD4+ lineage; the remaining CD8-positive T cells showed aberrant up-regulation of CD4+ lineage-associated genes including Cd4, Thpok, St8sia6, and Foxp3. Mechanistically, Tle3 bound to Runx-occupied Thpok silencer, in post-selection double-positive thymocytes to prevent excessive ThPOK induction and in mature CD8+ T cells to silence Thpok expression. Tle3 also bound to Tcf1-occupied sites in a few CD4+ lineage-associated genes, including Cd4 silencer and St8sia6 introns, to repress their expression in mature CD8+ T cells. These findings indicate that Tle corepressors are differentially partitioned to Runx and Tcf/Lef complexes to instruct CD8+ lineage choice and cooperatively establish CD8+ T cell identity, respectively.
Online Information of Parking Area Using Ultrasonic Sensor through Wifi Data Acquisition
Authors: Bagenda Dadan Nurdin , Parulian Crisyanto
Published: July 2018

Nowadays, malls and other public places in the city are facing problem in providing proper and huge parking area for their visitors’ vehicles. Also, the lack of human resource for the parkers makes the visitors difficult to find the available space to park their cars due to the less information they get during finding the parking space. Moreover, those who are seeking the parking space have to drive around the parking area for more than once, which is wasting their time a lot. Therefore, the malls and other public places need the best solution to this problem. The online parking information system is really needed to make the parking system better. This system uses a network sensor consisting of HC-SR04 ultrasonic module to detect the parking slot availability, HC-SR04 which is accessed by Arduino Nano, and the data that is sent to the server uses esp8266 wifi module. Further, the server processes the data and display the information on webpage application as well as desktop applications in the form of the parking area map. This system will show the available space that can be accessed on website and PC with a few second delays and simple wiring system.
Article Commentary: Sex- and Gender-Based Medicine: The Need for Precise Terminology
Authors: Madsen Tracy E. , Bourjeily Ghada , Hasnain Memoona , Jenkins Marjorie , Morrison Mary F. , Sandberg Kathryn , Tong Iris L. , Trott Justina , Werbinski Janice L. , McGregor Alyson J.
Published: July 2018

As our knowledge of sex- and gender-based medicine (SGBM) continues to grow, attention to precision in the use of related terminology is critical. Unfortunately, the terms sex and gender are often used interchangeably and incorrectly, both within and outside of the typical binary construct. On behalf of the Sex and Gender Women's Health Collaborative (SGWHC), a national organization whose mission is the integration of SGBM into research, health professions education, and clinical practice, our objective was to develop recommendations for the accurate use of SGBM terminology in research and clinical practice across medical specialties and across health professions. In addition, we reviewed the origins and evolution of SGBM terminology and described terms used when referring to individuals outside the typical binary categorization of sex and gender. Standardization and precision in the use of sex and gender terminology will lead to a greater understanding and appropriate translation of sex and gender evidence to patient care along with an accurate assessment of the impact sex and gender have on patient outcomes. In addition, it is critical to acknowledge that SGBM terminology will continue to evolve and become more precise as our knowledge of sex and gender differences in health and disease progresses.
Anticyclotomic 𝑝-adic 𝐿-functions and the exceptional zero phenomenon
Authors: Molina Santiago
Published: July 2018

Let

A
A

be a modular elliptic curve over a totally real field

F
F

, and let

K

/

F

K/F

be a totally imaginary quadratic extension. In the event of exceptional zero phenomenon, we prove a formula for the derivative of the multivariable anticyclotomic

p
p

-adic

L
L

-function attached to

(
A
,
K
)

(A,K)

, in terms of the Hasse-Weil

L
L

-function and certain

p
p

-adic periods attached to the respective automorphic forms. Our methods are based on a new construction of the anticyclotomic

p
p

-adic

L
L

-function by means of the corresponding automorphic representation.
A volume preserving flow and the isoperimetric problem in warped product spaces
Authors: Guan Pengfei , Li Junfang , Wang Mu-Tao
Published: July 2018

In this article, we continue the work in [Int. Math. Res. Not. IMRN 13 (2015), pp. 4716–4740] and study a normalized hypersurface flow in the more general ambient setting of warped product spaces. This flow preserves the volume of the bounded domain enclosed by a graphical hypersurface and monotonically decreases the hypersurface area. As an application, the isoperimetric problem in warped product spaces is solved for such domains.
Compactness of symmetric Markov semigroups and boundedness of eigenfunctions
Authors: Takeda Masayoshi
Published: July 2018

Let

X
X

be an irreducible

m
m

-symmetric Markov process on

E
E

with strong Feller property. In addition, suppose

X
X

has a tightness property. We then show that the semigroup of

X
X

is a compact operator on

L
2

(
E
;
m
)

L^2(E;m)

and every eigenfunction has a bounded continuous version.
Transition of responsive mechanosensitive elements from focal adhesions to adherens junctions on epithelial differentiation
Authors: Noethel Barbara , Ramms Lena , Dreissen Georg , Hoffmann Marco , Springer Ronald , Rübsam Matthias , Ziegler Wolfgang H. , Niessen Carien M. , Merkel Rudolf , Hoffmann Bernd
Published: July 2018

The skin’s epidermis is a multilayered epithelial tissue and the first line of defense against mechanical stress. Its barrier function depends on an integrated assembly and reorganization of cell–matrix and cell–cell junctions in the basal layer and on different intercellular junctions in suprabasal layers. However, how mechanical stress is recognized and which adhesive and cytoskeletal components are involved are poorly understood. Here, we subjected keratinocytes to cyclic stress in the presence or absence of intercellular junctions. Both states not only recognized but also responded to strain by reorienting actin filaments perpendicular to the applied force. Using different keratinocyte mutant strains that altered the mechanical link of the actin cytoskeleton to either cell–matrix or cell–cell junctions, we show that not only focal adhesions but also adherens junctions function as mechanosensitive elements in response to cyclic strain. Loss of paxillin or talin impaired focal adhesion formation and only affected mechanosensitivity in the absence but not presence of intercellular junctions. Further analysis revealed the adherens junction protein α-catenin as a main mechanosensor, with greatest sensitivity conferred on binding to vinculin. Our data reveal a mechanosensitive transition from cell–matrix to cell–cell adhesions on formation of keratinocyte monolayers with vinculin and α-catenin as vital players.
Replacing nonmuscle myosin 2A with myosin 2C1 permits gastrulation but not placenta vascular development in mice
Authors: Zhang Yingfan , Liu Chengyu , Adelstein Robert S. , Ma Xuefei
Published: July 2018

Three paralogues of nonmuscle myosin 2 (NM 2A, 2B, and 2C) are expressed in mammals, and the heavy chains are the products of three different genes (Myh9, Myh10, and Myh14, respectively). NM 2A and 2B are essential for mouse development, while 2C is not. Studies on NM 2C are limited and the in vivo function of this paralogue is not clear. Using homologous recombination, cDNA encoding nonmuscle myosin heavy chain 2C1 fused with GFP was introduced into the first coding exon of Myh9, replacing NM 2A expression with NM 2C1 expression in mice. In contrast to A–/A–embryos, which die by embryonic day (E) 6.5, AC1*gfp/AC1*gfpembryos survive through E8.5, demonstrating that NM 2C1 can support mouse development beyond gastrulation. At E9.5 and E10.5, however, AC1*gfp/AC1*gfpembryos are developmentally delayed, with abnormalities in placental vascular formation. The defect in vascular formation is confirmed in allantois explants from AC1*gfp/AC1*gfpembryos. Thus, NM 2C1 cannot support normal placental vascular formation. In addition, AC1*gfp/AC1*gfpmouse embryonic fibroblasts (MEFs) migrate rapidly but with impaired persistence and develop smaller, less mature focal adhesions than A+/A+MEFs. This is attributed to enhanced NM 2C1 actomyosin stability and different NM 2C1 subcellular localization than in NM 2A.
The role of traction in membrane curvature generation
Authors: Alimohamadi H. , Vasan R. , Hassinger J.E. , Stachowiak J.C. , Rangamani P.
Published: July 2018

Curvature of biological membranes can be generated by a variety of molecular mechanisms including protein scaffolding, compositional heterogeneity, and cytoskeletal forces. These mechanisms have the net effect of generating tractions (force per unit length) on the bilayer that are translated into distinct shapes of the membrane. Here, we demonstrate how the local shape of the membrane can be used to infer the traction acting locally on the membrane. We show that buds and tubes, two common membrane deformations studied in trafficking processes, have different traction distributions along the membrane and that these tractions are specific to the molecular mechanism used to generate these shapes. Furthermore, we show that the magnitude of an axial force applied to the membrane as well as that of an effective line tension can be calculated from these tractions. Finally, we consider the sensitivity of these quantities with respect to uncertainties in material properties and follow with a discussion on sources of uncertainty in membrane shape.
Roles of the fission yeast UNC-13/Munc13 protein Ync13 in late stages of cytokinesis
Authors: Zhu Yi-Hua , Hyun Joanne , Pan Yun-Zu , Hopper James E. , Rizo Josep , Wu Jian-Qiu
Published: July 2018

Cytokinesis is a complicated yet conserved step of the cell-division cycle that requires the coordination of multiple proteins and cellular processes. Here we describe a previously uncharacterized protein, Ync13, and its roles during fission yeast cytokinesis. Ync13 is a member of the UNC-13/Munc13 protein family, whose animal homologues are essential priming factors for soluble N-ethylmaleimide-sensitive factor attachment protein receptor complex assembly during exocytosis in various cell types, but no roles in cytokinesis have been reported. We find that Ync13 binds to lipids in vitro and dynamically localizes to the plasma membrane at cell tips during interphase and at the division site during cytokinesis. Deletion of Ync13 leads to defective septation and exocytosis, uneven distribution of cell-wall enzymes and components of cell-wall integrity pathway along the division site and massive cell lysis during cell separation. Interestingly, loss of Ync13 compromises endocytic site selection at the division plane. Collectively, we find that Ync13 has a novel function as an UNC-13/Munc13 protein in coordinating exocytosis, endocytosis, and cell-wall integrity during fission yeast cytokinesis.
Nutrient and drought stress: implications for phenology and biomass quality in miscanthus
Authors: da Costa Ricardo M F , Simister Rachael , Roberts Luned A , Timms-Taravella Emma , Cambler Arthur B , Corke Fiona M K , Han Jiwan , Ward Richard J , Buckeridge Marcos S , Gomez Leonardo D , Bosch Maurice
Published: July 2018

Background and Aims

The cultivation of dedicated biomass crops, including miscanthus, on marginal land provides a promising approach to the reduction of dependency on fossil fuels. However, little is known about the impact of environmental stresses often experienced on lower-grade agricultural land on cell-wall quality traits in miscanthus biomass crops. In this study, three different miscanthus genotypes were exposed to drought stress and nutrient stress, both separately and in combination, with the aim of evaluating their impact on plant growth and cell-wall properties.

Methods

Automated imaging facilities at the National Plant Phenomics Centre (NPPC-Aberystwyth) were used for dynamic phenotyping to identify plant responses to separate and combinatorial stresses. Harvested leaf and stem samples of the three miscanthus genotypes (Miscanthus sinensis, Miscanthus sacchariflorus and Miscanthus × giganteus) were separately subjected to saccharification assays, to measure sugar release, and cell-wall composition analyses.

Key Results

Phenotyping showed that the M. sacchariflorus genotype Sac-5 and particularly the M. sinensis genotype Sin-11 coped better than the M. × giganteus genotype Gig-311 with drought stress when grown in nutrient-poor compost. Sugar release by enzymatic hydrolysis, used as a biomass quality measure, was significantly affected by the different environmental conditions in a stress-, genotype- and organ-dependent manner. A combination of abundant water and low nutrients resulted in the highest sugar release from leaves, while for stems this was generally associated with the combination of drought and nutrient-rich conditions. Cell-wall composition analyses suggest that changes in fine structure of cell-wall polysaccharides, including heteroxylans and pectins, possibly in association with lignin, contribute to the observed differences in cell-wall biomass sugar release.

Conclusions

The results highlight the importance of the assessment of miscanthus biomass quality measures in addition to biomass yield determinations and the requirement for selecting suitable miscanthus genotypes for different environmental conditions.
Construction of an overexpression library for Mycobacterium tuberculosis
Authors: Melief Eduard , Kokoczka Rachel , Files Megan , Bailey Mai Ann , Alling Torey , Li Hongye , Ahn James , Misquith Ayesha , Korkegian Aaron , Roberts David , Sacchettini James , Parish Tanya
Published: July 2018

There is a pressing need to develop novel anti-tubercular drugs. High-throughput phenotypic screening yields chemical series that inhibit bacterial growth. Target identification for such series is challenging, but necessary for optimization of target engagement and the development of series into clinical drugs. We constructed a library of recombinant Mycobacterium tuberculosis strains each expressing a single protein from an inducible promoter as a tool for target identification. The library of 1733 clones was arrayed in 96-well plates for rapid screening and monitoring growth. The library contains the majority of the annotated essential genes as well as genes involved in cell wall and fatty acid biosynthesis, virulence factors, regulatory proteins, efflux, and respiration pathways. We evaluated the growth kinetics and plasmid stability over three passages for each clone in the library. We determined expression levels (mRNA and/or protein) in 396 selected clones. We screened the entire library and identified the Alr-expressing clone as the only recombinant strain, which grew in the presence of d-cycloserine (DCS). We confirmed that the Alr-expressing clone was resistant to DCS (7-fold shift in minimum inhibitory concentration). The library represents a new tool that can be used to screen for compound resistance and other phenotypes.
Transforming Access to Specialist Care for Inflammatory Bowel Disease: The PACE Telemedicine Program
Authors: Habashi Peter , Bouchard Shelley , Nguyen Geoffrey C
Published: July 2018

Background

There are significant geographic disparities in the delivery of IBD healthcare in Ontario which may ultimately impact health outcomes. Telemedicine-based health services may potentially bridge gaps in access to gastroenterologists in remote and underserved areas.

Methods

We conducted a needs assessment for IBD specialist care in Ontario using health administrative data. As part of a separate initiative to address geographic disparities in access to care, we described the development and implementation of our Promoting Access and Care through Centres of Excellence (PACE) Telemedicine Program. Over the first 18 months, we measured wait times and potential cost savings.

Results

We found substantial deficiencies in specialist care early in the course of IBD and continuous IBD care in regions where the number of gastroenterologists per capita were low. The PACE Telemedicine Program enabled new IBD consultations within a median time of 17 days (interquartile range [IQR], 7–32 days) and visits for active IBD symptoms with a median time of 8.5 days (IQR, 4–14 days). Forty-five percent of new consultations and 83% of patients with active IBD symptoms were seen within the target wait time of two weeks. Telemedicine services resulted in an estimated cost savings of $47,565 among individuals who qualified for Ontario’s Northern Travel Grant.

Conclusions

The implementation of telemedicine services for IBD is highly feasible and can reduce wait times to see gastroenterologists that meet nationally recommended targets and can lead to cost savings.
Stereotactic Body Radiotherapy for Spinal Metastases at the Extreme Ends of the Spine: Imaging-Based Outcomes for Cervical and Sacral Metastases
Authors: Zeng K Liang , Myrehaug Sten , Soliman Hany , Tseng Chia-Lin , Atenafu Eshetu G , Campbell Mikki , Faruqi Salman , Lee Young K , Ruschin Mark , da Costa Leodante , Yang Victor , Spears Julian , Heyn Chris , Maralani Pejman Jabehdar , Whyne Cari , Yee Albert , Sahgal Arjun
Published: July 2018

Background

The unique anatomy and biomechanical features of the cervical spine and sacrum may impact treatment outcomes following spine stereotactic body radiotherapy (SBRT). Current data for spine metastases are not specific for these locations.

Objective

To report imaging-based SBRT outcomes to cervical and sacral metastases.

Methods

We retrospectively reviewed our prospective spine SBRT database for cervical and sacral metastases. Patients were followed at 2- to 3-mo intervals with a clinical visit and full spine magnetic resonance imaging (MRI) and we report overall survival (OS), vertebral compression fracture (VCF), and MR imaging-based local control (LC) rates.

Results

Fifty-two patients and 93 treated spinal segments were identified. Fifty-six segments were within the cervical spine and 37 within the sacrum, the median follow-up was 14.4 and 19.5 mo, and the median total dose/number of fractions was 24 Gy/2, respectively. Cumulative LC at 1 and 2 yr were 94.5% and 92.7% for the cervical cohort, and 86.5% and 78.7% in the sacral cohort, respectively. Lack of posterior spinal element involvement in the cervical spine (P < .0001) and absence of epidural disease (hazard ratio 0.275, 95% confidence interval 0.076-0.989, P = .048) in the sacral cohort predicted LC. Median OS was 16.3 and 28.5 mo in the cervical spine and sacrum cohorts, respectively. Two cases of sacral VCF, 1 brachial plexopathy, and 1 lumbar-sacral plexopathy were observed.

CONCLUSION

Although high rates of LC were observed, strategies specific to the sacrum may require further optimization.
Knockout of tnni1b in zebrafish causes defects in atrioventricular valve development via the inhibition of the myocardial wnt signaling pathway
Authors: Cai Chen , Sang Caijun , Du Juan , Jia Haibo , Tu Jiayi , Wan Qing , Bao Binghao , Xie Shanglun , Huang Ying , Li Ao , Li Jiayu , Yang Kun , Wang Song , Lu Qunwei
Published: July 2018

The proper development of atrioventricular (AV) valves is critical for heart morphogenesis and for the formation of the cardiac conduction system. Defects in AV valve development are the most common type of congenital heart defect. Cardiac troponin I (ctnni), a structural and regulatory protein involved in cardiac muscle contraction, is a subunit of the troponin complex, but the functions and molecular mechanisms of ctnni during early heart development remain unclear. We created a knockout zebrafish model in which troponin I type 1b (tnnilb) (Tnni‐HC, heart and craniofacial) was deleted using the clustered regularly interspaced short palindromic repeat/clustered regularly interspaced short palindromic repeat‐associated protein system. In the homozygous mutant, the embryos showed severe pericardial edema, malformation of the heart tube, reduction of heart rate without contraction and with almost no blood flow, heart cavity congestion, and lack of an endocardial ring or valve leaflet, resulting in 88.8 ± 6.0% lethality at 7 d postfertilization. Deletion of tnni1b caused the abnormal expression of several markers involved in AV valve development, including bmp4, cspg2, has2, notch1b, spp1, and Alcam. Myocardial re‐expression of tnni1b in mutants partially rescued the pericardial edema phenotype and AV canal (AVC) developmental defects. We further showed that tnni1b knockout in zebrafish and ctnni knockdown in rat h9c2 myocardial cells inhibited cardiac wnt signaling and that myocardial reactivation of wnt signaling partially rescued the abnormal expression of AVC markers caused by the tnnilb deletion. Taken together, our data suggest that tnni1b plays a vital role in zebrafish AV valve development by regulating the myocardial wnt signaling pathway.—Cai, C., Sang, C., Du, J., Jia, H., Tu, J., Wan, Q., Bao, B., Xie, S., Huang, Y., Li, A., Li, J., Yang, K., Wang, S., Lu, Q. Knockout of tnnilb in zebrafish causes defects in atrioventricular valve development via the inhibition of myocardial wnt signaling pathway. FASEB J. 33, 696–710 (2019). www.fasebj.org
Regular Exercisers Have Stronger Pelvic Floor Muscles Than Nonregular Exercisers at Midpregnancy
Authors: Bø Kari , Ellstrøm Engh Marie , Hilde Gunvor
Published: July 2018

(Abstracted from Am J Obstet Gynecol 2018;218:427.e1–427.e5)

Clinicians encourage all healthy pregnant women to be physically active throughout pregnancy. Specific recommendations include participation in at least 30 minutes of aerobic activity most days of the week, strength training of the major muscle groups 2 to 3 days per week, and pelvic floor muscle (PFM) training.
Prospective Multicenter Study of a Multistep Screw Insertion Technique Using Patient-Specific Screw Guide Templates for the Cervical and Thoracic Spine
Authors: Sugawara Taku , Kaneyama Shuichi , Higashiyama Naoki , Tamura Shinya , Endo Takuro , Takabatake Masato , Sumi Masatoshi
Published: July 2018

Study Design.

A prospective clinical study of a multistep screw insertion method using a patient-specific screw guide template system (SGTS) for the cervical and thoracic spine.

Objective.

To evaluate the efficacy of SGTS for inserting screws into the cervical and thoracic spine.

Summary of Background Data.

Posterior screw fixation is a standard procedure for spinal instrumentation; however, screw insertion carries the risk of injury to neuronal and vascular structures.

Methods.

Preoperative bone images of the computed tomography (CT) scans were analyzed using 3D/multiplanar imaging software, and the screw trajectories were planned. Plastic templates with screw-guiding structures were created for each lamina using 3D design and printing technology. Three types of templates were made for precise multistep guidance, and all the templates were specially designed to fit and lock onto the lamina during the procedure. In addition, plastic vertebra models were generated, and preoperative screw insertion simulation was performed. This patient-specific SGTS was used to perform the surgery, and CT scanning was used to postoperatively evaluate screw placement.

Results.

Enrolled to verify this procedure were 103 patients with cervical, thoracic, or cervicothoracic pathologies. The SGTS were used to place 813 screws. Preoperatively, each template was found to fit exactly and to lock onto the lamina of the vertebra models. In addition, intraoperatively, the templates fit and locked onto the patient lamina, and the screws were inserted successfully. Postoperative CT scans confirmed that 801 screws (98.5%) were accurately placed without cortical violation. There were no injuries to the vessels or nerves.

Conclusion.

The multistep, patient-specific SGTS is useful for intraoperative pedicle screw (PS) navigation in the cervical and thoracic spine. This method improves the accuracy of PS insertion and reduces the operating time and radiation exposure during spinal fixation surgery.

Level of Evidence: 3
Systematic Evaluation of Neurotoxicity in Children and Young Adults Undergoing CD22 Chimeric Antigen Receptor T-Cell Therapy
Authors: Shalabi Haneen , Wolters Pamela L. , Martin Staci , Toledo-Tamula Mary Anne , Roderick Marie Claire , Struemph Kari , Kane Eli , Yates Bonnie , Delbrook Cindy , Mackall Crystal L. , Lee Daniel W. , Fry Terry J. , Shah Nirali N.
Published: July 2018

Neurotoxicity associated with CAR-T cell therapy can be life-threatening. With rapid development of CAR-T therapies, a systematic method is needed to identify and monitor symptoms of neurotoxicity, elucidate potential etiologies, and compare toxicity across trials. This paper presents a systematic evaluation developed and used to prospectively assess neurotoxicity in our phase I anti-CD22 CAR-T-cell trial and describes the symptoms of neurotoxicity identified using this methodology. Central nervous system (CNS) studies included routine lumbar punctures performed for disease evaluation pretherapy and posttherapy and a baseline brain MRI. Brief cognitive evaluations, assessing 4 domains (attention, working memory, cognitive flexibility, and processing speed), were administered preinfusion and postinfusion. A newly developed CAR-T-specific neurological symptom checklist (NSC) was completed by caregivers at 3 designated time-points. Serial serum cytokine levels were compared with neurotoxicity symptoms and severity. The majority of the first 22 consecutively treated subjects (ages, 7–30) demonstrated stable or improved cognitive test scores following therapy and no irreversible neurotoxicity, despite CAR-T-related antileukemic response, cytokine release syndrome, and trafficking of CAR-T cells to the CSF. The NSC allowed us to document the type and timing of symptoms and explore the etiology of neurotoxicity associated with CD22 CAR-T therapy. Cytokine profiling demonstrated that more concerning symptoms of neurotoxicity, such as hallucination and disorientation, were significantly associated with higher serum cytokine levels, supporting the hypothesis of inflammation-driven neurotoxicity. Systematic assessments of neurotoxicity were feasible in acutely ill children and young adults and served to characterize and monitor the symptoms associated with CAR-T therapy. We recommend these evaluations be incorporated into future immunotherapy protocols.
Pityriasis Rubra Pilaris With Extensive Follicular Acantholysis Resembling Pemphigus Vulgaris: A Case Report
Authors: Lilo Mohammed T. , Yan Shaofeng , Chapman Michael Shane , Linos Konstantinos
Published: July 2018

Pityriasis rubra pilaris (PRP) is a rare, chronic, heterogeneous, papulosquamous inflammatory dermatosis of unknown etiology. Although erythematous scaly patches characterize the classic presentation of PRP, a broad range of clinical presentations has been reported. Histologically, PRP is characterized by psoriasiform acanthosis with alternating orthokeratosis and parakeratosis and rarely small acantholytic foci. In this article, we report a patient who presented with diffuse erythroderma and extensive acantholysis mimicking pemphigus vulgaris histologically.
On the Use of Location and Occupancy Factors for Estimating External Exposure From Deposited Radionuclides
Authors: Tzivaki Margarita , Waller Edward
Published: July 2018

Providing a dose estimate for the exposed population is crucial in the case of deposition of a known radioactive material, either through an accident or during routine operations. In the absence of detailed information on each individual, knowing the demographics of the affected population concerning occupational habits and housing allows the determination and use of appropriate location and occupancy factors required for exposure and dose calculations. The previous approach in the United Nations Scientific Committee on the Effects of Atomic Radiation 2013 report, published in 2014, used time-dependent location factors and occupancy factors based on age and occupation. The newly published methodology in the United Nations Scientific Committee on the Effects of Atomic Radiation 2016 report (2017) is simplified, using a single time-independent location factor for indoor occupancy, as well as a single occupancy factor that is independent of the age and occupation of the population considered. In this work the two approaches are compared for different population groups and housing types in the case of both a short-lived and a long-lived radionuclide. It was found that the new simplified methodology, while overestimating the integrated effective dose over 100 y for 137Cs and 134Cs, also underestimates the dose on short timescales, especially for the shorter-lived 134Cs. Additionally, the dose rate is significantly underestimated for certain types of buildings with higher location factors. This was found for both radionuclides in the first year of exposure. In the case of short-lived 134Cs, the integrated effective dose after 100 y is also underestimated in certain cases. It can be concluded that, while the simplified methodology can reasonably and successfully be applied in cases where dose due to deposition (1) is not the dominant pathway and (2) is part of multistep calculations, caution must be exercised in more complex exposure situations, especially when performing dose assessment in response to an accident.
Mitigating the Psychological Harm from Actinide Intakes
Authors: Klumpp John A. , Bertelli Luiz , Hoffman Jeffrey , Poudel Deepesh , Waters Tom
Published: July 2018

Investigations into possible actinide intakes, as well as the intakes themselves, may result in significant psychological harm that should be mitigated by the internal dosimetrist. Many aspects of this psychological impact are unique to actinide intakes and have not been discussed in the literature. This paper discusses some of these unique considerations and describes how the Internal Dosimetry Team at Los Alamos National Laboratory (LANL) has, with input and guidance from LANL psychologists, tried to address them. We feel that much of the psychological harm can be mitigated by educating employees specifically about internal dosimetry and internal doses, and by improving communication with radiation workers.