bluuebunny/crossref_metadata_2025_split huggingface dataset:
Laboratory characterization of leukemic cell procoagulants
Authors: Hudák Renáta , Debreceni Ildikó Beke , Deák Ivett , Szabó Gabriella Gál , Hevessy Zsuzsanna , Antal-Szalmás Péter , Osterud Bjarne , Kappelmayer János 
Published: May 2017

AbstractBackground:In acute myeloid leukemias, there is an increased chance to develop thrombotic disorders. We hypothesized that in addition to leukemic promyelocytes, monocytic leukemia cells may also have a higher procoagulant activity.Methods:Fibrin formation was assessed by a one-stage clotting assay using a magnetic coagulometer. The thrombin generation test (TGT) of magnetically isolated normal human monocytes, intact leukemic cells and their isolated microparticles was performed by a fluorimetric assay. Phosphatidylserine (PS) expression of leukemic cells and microparticle number determinations were carried out by flow cytometry.Results:All cell lines displayed a significant procoagulant potential compared to isolated normal human monocytes. In the TGT test, the mean of lagtime and the time to peak parameters were significantly shorter in leukemic cells (3.9–4.7 and 9.9–10.3 min) compared to monocytes (14.9 and 26.5 min). The mean of peak thrombin in various monocytic leukemia cell lines was 112.1–132.9 nM vs. 75.1 nM in monocytes; however, no significant difference was observed in the ETP parameter. Factor VII-deficient plasma abolished all procoagulant activity, whereas factor XII-deficient plasma did not affect the speed of fibrin formation and thrombin generation but modulated the amount of thrombin. Factor XI-deficient plasma affected the time to peak values in one leukemic cell line and also attenuated peak thrombin. Leukemia cell-derived microparticles from all three cell lines exerted a procoagulant effect by significantly shortening the lagtime in TGT; there was a nonsignificant difference in case of ETP parameter.Conclusions:All investigated monocytic leukemia cell lines exhibited significant thrombin generation. This phenomenon was achieved by the procoagulants on the surface of leukemic cells as well as by their microparticles.
𝒟-modules arithmétiques sur la variété de drapeaux
Authors: Huyghe Christine , Schmidt Tobias 
Published: May 2017

Abstract
Soient p un nombre premier,
V un anneau de valuation discrète complet d’inégales caractéristiques

(
0
,
p
)

(0,p)

, et G un groupe réductif et deployé sur

Spec
⁡
V

\operatorname{Spec}V

.
Nous obtenons un théorème de localisation, en utilisant les distributions arithmétiques, pour le faisceau des opérateurs différentiels arithmétiques sur la variété de drapeaux formelle de G.
Nous donnons une application à la cohomologie rigide pour des ouverts dans la variété de drapeaux en caractéristique p.

Let p be a prime number, V a complete discrete valuation ring of unequal characteristics

(
0
,
p
)

(0,p)

, and G a connected split reductive algebraic group over

Spec
⁡
V

\operatorname{Spec}V

. We obtain a localization
theorem, involving arithmetic distributions, for the sheaf of arithmetic differential operators on the formal flag variety of G.
We give an application to the rigid cohomology of open subsets in the characteristic p flag variety.
Characteristics of carbon nanofibers produced from lignin/polyacrylonitrile (PAN)/kraft lignin-g-PAN copolymer blends electrospun nanofibers
Authors: Park Chan-Woo , Youe Won-Jae , Han Song-Yi , Kim Yong Sik , Lee Seung-Hwan 
Published: May 2017

AbstractLignin-based electrospun nanofibers (eNFs) were prepared and thermally stabilized at 250°C and subsequently carbonized at 1400°C. The starting blend was prepared in dimethyl formamide (DMF) solution with lignin and polyacrylonitrile (PAN), while a lignin-grafted-PAN (L-g-PAN) copolymer served as compatibilizer. The viscosity was highest of the DMF solution with PAN, and decreased for the lignin/PAN blends and additionally in presence of L-g-PAN. The uniform eNFs with clean surfaces dispose of diameters between 400 nm and 1 μm. The average diameter of eNFs decreased by the thermal treatment and at higher lignin contents in the blends. Remarkable shrinkage by carbonization was observed in all nanofibers. The successful carbonization of all electrospun carbon nanofibers (eCNFs) was confirmed by Fourier transform-infrared (FT-IR) spectroscopy. The specific tensile strength and elastic modulus of the eCNF mats from lignin/PAN blends were improved by the addition of L-g-PAN, and it can be safely concluded that it acts as a compatibilizer between lignin and PAN.
Appearance of inaccurate results in the MUSIC algorithm with inappropriate wavenumber
Authors: Park Won-Kwang 
Published: May 2017

Abstract
MUltiple SIgnal Classification (MUSIC) is a well-known non-iterative location detection algorithm for small, perfectly conducting cracks in inverse scattering problems. However, when the applied wavenumbers are unknown, inaccurate locations of targets are extracted by MUSIC with inappropriate wavenumbers, a fact that has been confirmed by numerical simulations. To date, the reason behind this phenomenon has not been theoretically investigated. Motivated by this fact, we identify the structure of MUSIC-type imaging functionals with inappropriate wavenumbers by establishing a relationship with Bessel functions of order zero of the first kind. This result explains the reasons for inaccurate results. Various results of numerical simulations with noisy data support the identified structure of MUSIC.
Macedonia’s colourful revolution and the elections of 2016. A chance for democracy, or all for nothing?
Authors: Reef Paul 
Published: May 2017

Abstract
This article analyses Macedonia’s Colourful Revolution and elections of 2016 against the background of the criticism and protests directed against the Skopje 2014 Project. It also provides a photographic reportage of Skopje 2014 during the political turmoil from July 2016. It examines the main grounds for resistance and opposition to Nikola Gruevski’s VMRO-DPMNE government by further investigating the controversies surrounding Skopje 2014. Those controversies are manifold but stem mainly from the project’s tremendous cost and corruption, its controversial rewriting of history and its exclusion of Albanians and other minorities. Finally, the article argues that the Colourful Revolution has until now failed to overturn or decisively upset Macedonia’s politics or political system, as is evident from election results there. However, it has borne fruit in one respect in that two Albanian MPs have been included in the Social Democratic Union of Macedonia (SDSM), a tentative step towards overcoming the ethnic deadlock of Macedonian politics.
The Relationship Between the Push Off Ground Reaction Force and Ball Speed in High School Baseball Pitchers
Authors: Oyama Sakiko , Myers Joseph B. 
Published: May 2017

Abstract
Oyama, S and Myers, JB. The relationship between the push off ground reaction force and ball speed in high school baseball pitchers. J Strength Cond Res 32(5): 1324–1328, 2018—Baseball pitching is a sequential movement that requires transfer of momentum from the lower extremity to the throwing arm. Therefore, the ground reaction force (GRF) during push off is suggested to play a role in production of ball speed. The purpose of this study was to investigate the correlation between GRF characteristics during push off and ball speed in high school baseball pitchers. A total of 52 pitchers performed fast pitches from an indoor pitching mound. A force plate embedded in an indoor mound was used to capture the push off GRF. The GRF characteristics (peak anterior, vertical, and resultant forces, vertical and resultant forces at the time of peak anterior GRF, and impulse produced by the anterior GRF) from the 3 fastest strike pitches from each pitcher were used for analyses. Spearman's rank correlation coefficients were used to describe the relationships between ball speed and the GRF characteristics. Ball speed was only weakly correlated with peak resultant force (ρ = 0.32, p = 0.02) and vertical (ρ = 0.45, p < 0.001) and resultant (ρ = 0.42, p = 0.002) forces at the time of peak anterior force. The ball speed was not correlated with other variables. The correlation between ball speed and push off force in high school pitchers was weak, especially when compared with what was reported for adult pitchers in other studies. Unlike for adult pitchers, higher push off force is only weakly correlated with ball velocity in high school pitchers, which suggests that training to better use body momentum may help high school pitchers improve ball speed.
Aerobic Exercise Supplemented With Muscular Endurance Training Improves Onset of Blood Lactate Accumulation
Authors: Farrell John W. , Lantis David J. , Ade Carl J. , Cantrell Greg S. , Larson Rebecca D. 
Published: May 2017

Abstract
Farrell III, JW, Lantis, DJ, Ade, CJ, Cantrell, GS, and Larson, RD. Aerobic exercise supplemented with muscular endurance training improves onset of blood lactate accumulation. J Strength Cond Res 32(5): 1376–1382, 2018—Studies have shown that when aerobic exercise is supplemented with muscular endurance training metabolic adaptions occur that result in the delay of the onset of blood lactate accumulation (OBLA). However, previous studies have not explored any submaximal cardiorespiratory adaptations that may result from this training protocol. The aim of the current investigation was to evaluate the effect of supplementing an aerobic exercise training program with a muscular endurance training program on various cardiorespiratory and metabolic measurements. Fourteen aerobically active men performed an incremental exercise test to determine the OBLA, gas exchange threshold (GET), and maximal oxygen uptake (V̇o
2max). Maximal strength was measured using 1 repetition maximum (1RM) for leg press (LP), leg curl (LC), and leg extension (LE). Eight subjects supplemented their aerobic activity (experimental [EX] group) with 8 weeks of muscular endurance training, while 6 continued their regular aerobic activity (control [CON] group). No significant group differences were observed for all pretraining variables. After 8 weeks of training, no significant differences in body mass, GET, and V̇o
2max were observed for either group. However, the EX group showed a significant improvement for both absolute and relative V̇o
2 at OBLA compared with the CON group. Leg curl and LE 1RM assessments for the EX group showed a significant improvement compared with CON group. Muscular endurance training did not improve GET and V̇o
2max, but significantly increased V̇o
2 at OBLA, LP, and LC. These findings suggest that this training protocol maybe useful in the development of submaximal aerobic performance and leg strength for endurance athletes.
Angiotensin IV Receptors Mediate the Cognitive and Cerebrovascular Benefits of Losartan in a Mouse Model of Alzheimer's Disease
Authors: Royea Jessika , Zhang Luqing , Tong Xin-Kang , Hamel Edith 
Published: May 2017

The use of angiotensin receptor blockers (ARBs) correlates with reduced onset and progression of Alzheimer's disease (AD). The mechanism depicting how ARBs such as losartan restore cerebrovascular and cognitive deficits in AD is unknown. Here, we propose a mechanism underlying losartan's benefits by selectively blocking the effects of angiotensin IV (AngIV) at its receptor (AT4R) with divalinal in mice overexpressing the AD-related Swedish and Indiana mutations of the human amyloid precursor protein (APP mice) and WT mice. Young (3-month-old) mice were treated with losartan (∼10 mg/kg/d, 4 months), followed by intracerebroventricular administration of vehicle or divalinal in the final month of treatment. Spatial learning and memory were assessed using Morris water mazes at 3 and 4 months of losartan treatment. Cerebrovascular reactivity and whisker-evoked neurovascular coupling responses were measured at end point (∼7 months of age), together with biomarkers related to neuronal and vascular oxidative stress (superoxide dismutase-2), neuroinflammation (astroglial and microglial activation), neurogenesis (BrdU-labeled newborn cells), and amyloidosis [soluble amyloid-β (Aβ) species and Aβ plaque load]. Divalinal countered losartan's capacity to rescue spatial learning and memory and blocked losartan's benefits on dilatory function and baseline nitric oxide bioavailability. Divalinal reverted losartan's anti-inflammatory effects, but failed to modify losartan-mediated reductions in oxidative stress. Neither losartan nor divalinal affected arterial blood pressure or significantly altered the amyloid pathology in APP mice. Our findings identify activation of the AngIV/AT4R cascade as the underlying mechanism in losartan's benefits and a target that could restore Aβ-related cognitive and cerebrovascular deficits in AD.SIGNIFICANCE STATEMENTAntihypertensive medications that target the renin angiotensin system, such as angiotensin receptor blockers (ARBs), have been associated with lower incidence and progression of Alzheimer's disease (AD) in cohort studies. However, the manner by which ARBs mediate their beneficial effects is unknown. Here, the angiotensin IV receptor (AT4R) was identified as mediating the cognitive and cerebrovascular rescue of losartan, a commonly prescribed ARB, in a mouse model of AD. The AT4R was further implicated in mediating anti-inflammatory benefits. AT4R-mediated effects were independent from changes in blood pressure, amyloidosis, and oxidative stress. Overall, our results implicate the angiotensin IV/AT4R cascade as a promising candidate for AD intervention.
In VivoCalcium Signaling during Synaptic Refinement at theDrosophilaNeuromuscular Junction
Authors: Vonhoff Fernando , Keshishian Haig 
Published: May 2017

Neural activity plays a key role in pruning aberrant synapses in various neural systems, including the mammalian cortex, where low-frequency (0.01 Hz) calcium oscillations refine topographic maps. However, the activity-dependent molecular mechanisms remain incompletely understood. Activity-dependent pruning also occurs at embryonicDrosophilaneuromuscular junctions (NMJs), where low-frequency Ca2+oscillations are required for synaptic refinement and the response to the muscle-derived chemorepellant Sema2a. We examined embryonic growth cone filopodiain vivoto directly observe their exploration and to analyze the episodic Ca2+oscillations involved in refinement. Motoneuron filopodia repeatedly contacted off-target muscle fibers over several hours during late embryogenesis, with episodic Ca2+signals present in both motile filopodia as well as in later-stabilized synaptic boutons. The Ca2+transients matured over several hours into regular low-frequency (0.03 Hz) oscillations.In vivoimaging of intact embryos of both sexes revealed that the formation of ectopic filopodia is increased inSema2aheterozygotes. We provide genetic evidence suggesting a complex presynaptic Ca2+-dependent signaling network underlying refinement that involves the phosphatases calcineurin and protein phosphatase-1, as well the serine/threonine kinases CaMKII and PKA. Significantly, this network influenced the neuron's response to the muscle's Sema2a chemorepellant, critical for the removal of off-target contacts.SIGNIFICANCE STATEMENTTo address the question of how synaptic connectivity is established during development, we examined the behavior of growth cone filopodia during the exploration of both correct and off-target muscle fibers inDrosophilaembryos. We demonstrate that filopodia repeatedly contact off-target muscles over several hours, until they ultimately retract. We show that intracellular signals are observed in motile and stabilized “ectopic” contacts. Several genetic experiments provide insight in the molecular pathway underlying network refinement, which includes oscillatory calcium signals via voltage-gated calcium channels as a key component. Calcium orchestrates the activity of several kinases and phosphatases, which interact in a coordinated fashion to regulate chemorepulsion exerted by the muscle.
Toward an Information Infrastructure for Global Health Improvement
Authors: Friedman C. P. , Rubin J. C. , Sullivan K. J. 
Published: May 2017

SummaryProfound global challenges to individual and population health, alongside the opportunities to benefit from digital technology, have spawned the concept of the Learning Health System. Learning Health Systems (LHSs)--which can function at organizational, network, regional, and national levels of scale--have the capability of continuous data-driven self-study that promotes change and improvement. The LHS concept, which originated in the U.S. in 2007, is rapidly gaining attention around the world. LHSs require, but also transcend, the secondary use of health data. This paper describes the key features of LHSs, argues that effective and sustainable LHSs must be supported by infrastructures that allow them to function with economies of scale and scope, and describes the services that such infrastructures must provide. While it is relatively straightforward to describe LHSs, achieving them at the high level of capability necessary to promote significant health benefits will require advancements in science and engineering, engaging the field of informatics among a wider range of disciplines. It also follows from this vision that LHSs cannot be built from an imposed blueprint; LHSs will more likely evolve from efforts at smaller scales that compose into larger systems.
The Immune Phenotype of ThreeDrosophilaLeukemia Models
Authors: Arefin Badrul , Kunc Martin , Krautz Robert , Theopold Ulrich 
Published: May 2017

AbstractMany leukemia patients suffer from dysregulation of their immune system, making them more susceptible to infections and leading to general weakening (cachexia). Both adaptive and innate immunity are affected. The fruit fly Drosophila melanogaster has an innate immune system, including cells of the myeloid lineage (hemocytes). To study Drosophila immunity and physiology during leukemia, we established three models by driving expression of a dominant-active version of the Ras oncogene (RasV12) alone or combined with knockdowns of tumor suppressors in Drosophila hemocytes. Our results show that phagocytosis, hemocyte migration to wound sites, wound sealing, and survival upon bacterial infection of leukemic lines are similar to wild type. We find that in all leukemic models the two major immune pathways (Toll and Imd) are dysregulated. Toll–dependent signaling is activated to comparable extents as after wounding wild-type larvae, leading to a proinflammatory status. In contrast, Imd signaling is suppressed. Finally, we notice that adult tissue formation is blocked and degradation of cell masses during metamorphosis of leukemic lines, which is akin to the state of cancer-dependent cachexia. To further analyze the immune competence of leukemic lines, we used a natural infection model that involves insect-pathogenic nematodes. We identified two leukemic lines that were sensitive to nematode infections. Further characterization demonstrates that despite the absence of behavioral abnormalities at the larval stage, leukemic larvae show reduced locomotion in the presence of nematodes. Taken together, this work establishes new Drosophila models to study the physiological, immunological, and behavioral consequences of various forms of leukemia.
Mathematical Constraints on FST: Biallelic Markers in Arbitrarily Many Populations
Authors: Alcala Nicolas , Rosenberg Noah A 
Published: May 2017

Abstract
F ST is one of the most widely used statistics in population genetics. Recent mathematical studies have identified constraints that challenge interpretations of FST as a measure with potential to range from 0 for genetically similar populations to 1 for divergent populations. We generalize results obtained for population pairs to arbitrarily many populations, characterizing the mathematical relationship between FST, the frequency M of the more frequent allele at a polymorphic biallelic marker, and the number of subpopulations K. We show that for fixed K, FST has a peculiar constraint as a function of M, with a maximum of 1 only if M=i/K, for integers i with ⌈K/2⌉≤i≤K−1. For fixed M, as K grows large, the range of FST becomes the closed or half-open unit interval. For fixed K, however, some M&lt;(K−1)/K always exists at which the upper bound on FST lies below 22−2≈0.8284. We use coalescent simulations to show that under weak migration, FST depends strongly on M when K is small, but not when K is large. Finally, examining data on human genetic variation, we use our results to explain the generally smaller FST values between pairs of continents relative to global FST values. We discuss implications for the interpretation and use of FST.
Regulatory Mechanisms of Metamorphic Neuronal Remodeling Revealed Through a Genome-Wide Modifier Screen in Drosophila melanogaster
Authors: Chen Dahong , Gu Tingting , Pham Tom N , Zachary Montgomery J , Hewes Randall S 
Published: May 2017

Abstract
During development, neuronal remodeling shapes neuronal connections to establish fully mature and functional nervous systems. Our previous studies have shown that the RNA-binding factor alan shepard (shep) is an important regulator of neuronal remodeling during metamorphosis in Drosophila melanogaster, and loss of shep leads to smaller soma size and fewer neurites in a stage-dependent manner. To shed light on the mechanisms by which shep regulates neuronal remodeling, we conducted a genetic modifier screen for suppressors of shep-dependent wing expansion defects and cellular morphological defects in a set of peptidergic neurons, the bursicon neurons, that promote posteclosion wing expansion. Out of 702 screened deficiencies that covered 86% of euchromatic genes, we isolated 24 deficiencies as candidate suppressors, and 12 of them at least partially suppressed morphological defects in shep mutant bursicon neurons. With RNA interference and mutant alleles of individual genes, we identified Daughters against dpp (Dad) and Olig family (Oli) as shep suppressor genes, and both of them restored the adult cellular morphology of shep-depleted bursicon neurons. Dad encodes an inhibitory Smad protein that inhibits bone morphogenetic protein (BMP) signaling, raising the possibility that shep interacted with BMP signaling through antagonism of Dad. By manipulating expression of the BMP receptor tkv, we found that activated BMP signaling was sufficient to rescue loss-of-shep phenotypes. These findings reveal mechanisms of shep regulation during neuronal development, and they highlight a novel genetic shep interaction with the BMP signaling pathway that controls morphogenesis in mature, terminally differentiated neurons during metamorphosis.