bluuebunny/crossref_metadata_2025_split huggingface dataset:
Extracellular matrix: the gatekeeper of tumor angiogenesis
Authors: Mongiat Maurizio , Buraschi Simone , Andreuzzi Eva , Neill Thomas , Iozzo Renato V. 
Published: October 2019

Abstract
The extracellular matrix is a network of secreted macromolecules that provides a harmonious meshwork for the growth and homeostatic development of organisms. It conveys multiple signaling cascades affecting specific surface receptors that impact cell behavior. During cancer growth, this bioactive meshwork is remodeled and enriched in newly formed blood vessels, which provide nutrients and oxygen to the growing tumor cells. Remodeling of the tumor microenvironment leads to the formation of bioactive fragments that may have a distinct function from their parent molecules, and the balance among these factors directly influence cell viability and metastatic progression. Indeed, the matrix acts as a gatekeeper by regulating the access of cancer cells to nutrients. Here, we will critically evaluate the role of selected matrix constituents in regulating tumor angiogenesis and provide up-to-date information concerning their primary mechanisms of action.
GDF11 impairs liver regeneration in mice after partial hepatectomy
Authors: Wang Wenjie , Yang Xiao , Yang Jiankun , Liu Shenpei , Lv Yongman , Zhang Cuntai , Dong Wei , Liu Anding 
Published: October 2019

Abstract
Growth differentiation factor 11 (GDF11) is a member of the transforming growth factor (TGF)-β superfamily. The rejuvenative effect of GDF11 has been called into question recently, and its role in liver regeneration is unclear. Here, we investigated the pathophysiologic role of GDF11, as well as its plausible signaling mechanisms in a mouse model of partial hepatectomy (PH). We demonstrated that both serum and hepatic GDF11 protein expression increased following PH. Treatment with adeno-associated viruses-GDF11 and recombinant GDF11 protein severely impaired liver regeneration, whereas inhibition of GDF11 activity with neutralizing antibodies significantly improved liver regeneration after PH. In vitro, GDF11 treatment significantly delayed cell proliferation and induced cell-cycle arrest in α mouse liver 12 (AML12) cells. Moreover, GDF11 activated TGF-β-SMAD2/3 signaling pathway. Inhibition of GDF11-induced SMAD2/3 activity significantly blocked GDF11-mediated reduction in cell proliferation both in vivo and in vitro. In the clinical setting, GDF11 levels were significantly elevated in patients after hepatectomy. Collectively, these results indicate that rather than a ‘rejuvenating’ agent, GDF11 impairs liver regeneration after PH. Suppression of cell-cycle progression via TGF-β-SMAD2/3 signaling pathway may be a key mechanism by which GDF11 inhibits liver regeneration.
Endogenous hydrogen sulfide sulfhydrates IKKβ at cysteine 179 to control pulmonary artery endothelial cell inflammation
Authors: Zhang Da , Wang Xiuli , Chen Siyao , Chen Selena , Yu Wen , Liu Xin , Yang Guosheng , Tao Yinghong , Tang Xinjing , Bu Dingfang , Zhang Heng , Kong Wei , Tang Chaoshu , Huang Yaqian , Du Junbao , Jin Hongfang 
Published: October 2019

Abstract
Background: Pulmonary artery endothelial cell (PAEC) inflammation is a critical event in the development of pulmonary arterial hypertension (PAH). However, the pathogenesis of PAEC inflammation remains unclear.
Methods: Purified recombinant human inhibitor of κB kinase subunit β (IKKβ) protein, human PAECs and monocrotaline-induced pulmonary hypertensive rats were employed in the study. Site-directed mutagenesis, gene knockdown or overexpression were conducted to manipulate the expression or activity of a target protein.
Results: We showed that hydrogen sulfide (H2S) inhibited IKKβ activation in the cell model of human PAEC inflammation induced by monocrotaline pyrrole-stimulation or knockdown of cystathionine γ-lyase (CSE), an H2S generating enzyme. Mechanistically, H2S was proved to inhibit IKKβ activity directly via sulfhydrating IKKβ at cysteinyl residue 179 (C179) in purified recombinant IKKβ protein in vitro, whereas thiol reductant dithiothreitol (DTT) reversed H2S-induced IKKβ inactivation. Furthermore, to demonstrate the significance of IKKβ sulfhydration by H2S in the development of PAEC inflammation, we mutated C179 to serine (C179S) in IKKβ. In purified IKKβ protein, C179S mutation of IKKβ abolished H2S-induced IKKβ sulfhydration and the subsequent IKKβ inactivation. In human PAECs, C179S mutation of IKKβ blocked H2S-inhibited IKKβ activation and PAEC inflammatory response. In pulmonary hypertensive rats, C179S mutation of IKKβ abolished the inhibitory effect of H2S on IKKβ activation and pulmonary vascular inflammation and remodeling.
Conclusion: Collectively, our in vivo and in vitro findings demonstrated, for the first time, that endogenous H2S directly inactivated IKKβ via sulfhydrating IKKβ at Cys179 to inhibit nuclear factor-κB (NF-κB) pathway activation and thereby control PAEC inflammation in PAH.
SETD3 is regulated by a couple of microRNAs and plays opposing roles in proliferation and metastasis of hepatocellular carcinoma
Authors: Xu Liangliang , Wang Peng , Feng Xinfu , Tang Jianwei , Li Lian , Zheng Xiaobo , Zhang Jinfu , Hu Yitao , Lan Tian , Yuan Kefei , Zhang Yanfang , Ren Shengsheng , Hao Xiangyong , Zhang Ming , Xu Mingqing 
Published: October 2019

Abstract
A previous study reported that histone methyltransferase SETD3 is up-regulated in tumor tissues of hepatocellular carcinoma (HCC) and is associated with the growth of HCC. However, the clinical significance and the effect of SETD3 on HCC metastasis remain unclear. In the present study, both the protein and mRNA expression levels of SETD3 were measured in a larger cohort of HCC patients. The results showed that the protein level of SETD3 in HCC tissues was significantly higher than that in non-tumorous tissues, which was inconsistent with the mRNA expression level of SETD3. The high protein level of SETD3 in HCC tissues was significantly associated with male gender, poor pathological differentiation, liver cirrhosis and unfavorable prognosis of HCC patients. Subsequently, we demonstrated that SETD3 could be regulated at post-transcriptional step by a couple of miRNAs (miR-16, miR-195 and miR-497). Additionally, in vitro and in vivo experiments revealed that SETD3 played opposing roles in proliferation and metastasis of HCC: promoting proliferation but inhibiting metastasis. Mechanistic experiments revealed that doublecortin-like kinase 1 (DCLK1) was a downstream target of SETD3. SETD3 could increase the DNA methylation level of DCLK1 promoter to inhibit the transcription of DCLK1. Further study revealed that DCLK1/PI3K/matrix metalloproteinase (MMP) 2 (MMP-2) was an important pathway that mediated the effect of SETD3 on HCC metastasis. In conclusion, the present study revealed that SETD3 is associated with tumorigenesis and is a promising biomarker for predicting the prognosis of HCC patients after surgical resection. In addition, SETD3 plays inhibitory role in HCC metastasis partly through DCLK1/PI3K/MMP-2 pathway.
A novel function for HEG1 in promoting metastasis in hepatocellular carcinoma
Authors: Dewdney Brittany , Hebbard Lionel 
Published: October 2019

Abstract
Hepatocellular carcinoma (HCC) remains one of the leading causes of cancer-related deaths around the globe. For patients receiving liver tumour resection, the risk of reoccurrence and metastasis is high. Cancer metastasis can occur as a consequence of a physical change known as epithelial to mesenchymal transition (EMT). In this instance, cancer cells acquire migratory and invasive characteristics that allow the cells to move into adjacent tissue or enter the bloodstream to reach a secondary site, where they begin to form a new tumour. Targetting proteins involved in the signalling pathways that induce the mesenchymal phenotype has been an ongoing field of research. A recently published study has described a novel role for the heart development protein with EGF-like domains (HEG1) in promoting EMT. This research provides new insights into the biological function of this protein in HCC. Furthermore, the research indicates a new target for future prognostic and therapeutic research in HCC.
Keratin intermediate filaments: intermediaries of epithelial cell migration
Authors: Yoon Sungjun , Leube Rudolf E. 
Published: October 2019

Abstract
Migration of epithelial cells is fundamental to multiple developmental processes, epithelial tissue morphogenesis and maintenance, wound healing and metastasis. While migrating epithelial cells utilize the basic acto-myosin based machinery as do other non-epithelial cells, they are distinguished by their copious keratin intermediate filament (KF) cytoskeleton, which comprises differentially expressed members of two large multigene families and presents highly complex patterns of post-translational modification. We will discuss how the unique mechanophysical and biochemical properties conferred by the different keratin isotypes and their modifications serve as finely tunable modulators of epithelial cell migration. We will furthermore argue that KFs together with their associated desmosomal cell–cell junctions and hemidesmosomal cell–extracellular matrix (ECM) adhesions serve as important counterbalances to the contractile acto-myosin apparatus either allowing and optimizing directed cell migration or preventing it. The differential keratin expression in leaders and followers of collectively migrating epithelial cell sheets provides a compelling example of isotype-specific keratin functions. Taken together, we conclude that the expression levels and specific combination of keratins impinge on cell migration by conferring biomechanical properties on any given epithelial cell affecting cytoplasmic viscoelasticity and adhesion to neighboring cells and the ECM.
Precision requirements for interferometric gridding in the analysis of a 21 cm power spectrum
Authors: Offringa A. R. , Mertens F. , van der Tol S. , Veenboer B. , Gehlot B. K. , Koopmans L. V. E. , Mevius M. 
Published: October 2019

Context. Experiments that try to observe the 21 cm redshifted signals from the epoch of reionisation (EoR) using interferometric low-frequency instruments have stringent requirements on the processing accuracy.
Aims. We analyse the accuracy of radio interferometric gridding of visibilities with the aim to quantify the power spectrum bias caused by gridding. We do this ultimately to determine the suitability of different imaging algorithms and gridding settings for an analysis of a 21 cm power spectrum.
Methods. We simulated realistic Low-Frequency Array (LOFAR) data and constructed power spectra with convolutional gridding and w stacking, w projection, image-domain gridding, and without w correction. These were compared against data that were directly Fourier transformed. The influence of oversampling, kernel size, w-quantization, kernel windowing function, and image padding were quantified. The gridding excess power was measured with a foreground subtraction strategy, for which foregrounds were subtracted using Gaussian progress regression, as well as with a foreground avoidance strategy.
Results. Constructing a power spectrum with a significantly lower bias than the expected EoR signals is possible with the methods we tested, but requires a kernel oversampling factor of at least 4000, and when w-correction is used, at least 500 w-quantization levels. These values are higher than typically used values for imaging, but they are computationally feasible. The kernel size and padding factor parameters are less crucial. Of the tested methods, image-domain gridding shows the highest accuracy with the lowest imaging time.
Conclusions. LOFAR 21 cm power spectrum results are not affected by gridding. Image-domain gridding is overall the most suitable algorithm for 21 cm EoR power spectrum experiments, including for future analyses of data from the Square Kilometre Array (SKA) EoR. Nevertheless, convolutional gridding with tuned parameters results in sufficient accuracy for interferometric 21 cm EoR experiments. This also holds for w stacking for wide-field imaging. The w-projection algorithm is less suitable because of the requirements for kernel oversampling, and a faceting approach is unsuitable because it causes spatial discontinuities.
The impact of thermal winds on the outburst lightcurves of black hole X-ray binaries
Authors: Dubus Guillaume , Done Chris , Tetarenko Bailey E. , Hameury Jean-Marie 
Published: October 2019

Context. The observed signatures of winds from X-ray binaries are broadly consistent with thermal winds, which are driven by X-ray irradiation of the outer accretion disc. Thermal winds produce mass outflow rates that can exceed the accretion rate in the disc.
Aims. We aim to study the impact of thermal wind mass loss on the stability and lightcurves of black hole X-ray binaries subject to the thermal-viscous instability driving their outbursts. Strong mass loss could stop outbursts early, as proposed for the 2015 outburst of V404 Cyg.
Methods. We used an analytical model for thermal (Compton) wind mass loss as a function of radius, X-ray spectrum, and luminosity that was calibrated against numerical simulations. We also estimated the fraction of the X-rays, emitted close to the compact object, that are scattered back to the outer disc in the wind. Scattering in the thermal wind couples irradiation to the disc size and inner mass accretion rate. The disc evolution equations were modified to include this wind mass loss and the varying irradiation fraction.
Results. Scattering in the strong wind expected of long Porb systems enhances the irradiation heating of the outer disc, keeping it stable against the thermal-viscous instability. This accounts very well for the existence of persistently bright systems with large discs, such as Cyg X-2, 1E 1740.7−2942, or GRS 1758−258. Mass loss from the thermal wind shortens the outburst, as expected, but it is insufficient in explaining the rapid decay timescale of black-hole X-ray binary outbursts. However, including the wind-related varying irradiation fraction produces lightcurves with plateaus in long Porb systems like GRO J1655−40. Plateau lightcurves may be a dynamical signature of enhanced irradiation due to scattering in thermal winds.
Conclusions. Mass loss due to thermal winds is not a major driver for the outburst dynamics up to luminosities of 0.1 − 0.2 LEdd. Higher luminosities may produce stronger mass loss but studying them is complicated since the wind becomes opaque. Magnetic winds, which extract angular momentum with little mass loss, seem more promising to explain the fast decay timescales generically seen in black-hole X-ray binaries. Thermal winds can play an important role in the outburst dynamics through the varying irradiation heating. This may be evidenced by relating changes in wind properties, X-ray spectra, or luminosity with changes in the optical emission that traces the outer disc. Simulations should enable more accurate estimates of the dependence of the irradiation onto the disc as a function of irradiation spectrum, radius, and disc wind properties.
Optimierung der Adhärenz von Patienten nach Nierentransplantation
Authors: Matevossian Edouard , Miksch Rainer Christoph 
Published: October 2019

ZUSAMMENFASSUNGEine mangelnde Adhärenz bzw. Compliance in der Arzneimitteltherapie kann eine erhöhte Morbidität und Mortalität sowie gewaltige Kosten im Gesundheitssystem verursachen. Fördernde Maßnahmen zur Adhärenz bzw. Compliance können in der Arzneimitteltherapie mit langfristig positivem Effekt auf den Therapieerfolg angewendet werden. Die Gemeinsamkeit aller dieser Interventionen liegt in einem gehäuften gezielten Kontakt von Leistungserbringern im Gesundheitssystem und Patienten im Laufe der Therapie hinsichtlich ihrer Adhärenz bzw. Compliance. Da die Prävalenz chronischer Erkrankungen in den nächsten Jahrzehnten weiter zunehmen wird, sind Maßnahmen zur Verbesserung der Adhärenz wichtig, um die Gesundheit der Bevölkerung nachhaltig zu verbessern – aber auch, um die Kosten für die Gesundheitssysteme nicht weiter explodieren zu lassen.
Imaging Spectrum of Pediatric Nonspecific Aortoarteritis on CT Angiography: A Retrospective Study
Authors: Verma Ashish , Kumar Ishan , Aggarwal Priyanka , Shukla Ram C. 
Published: October 2019

Introduction
Takayasu's arteritis, a chronic, idiopathic, inflammatory panarteritis, is the major cause of Aortoarteritis in pediatric age group. The purpose of this study is to analyze the patterns of involvement and imaging findings of pediatric Takayasu's arteritis.

Materials and Methods
We retrospectively reviewed the CT angiographic images of 11 pediatric cases reported as “Takayasu's arteritis” or “nonspecific arteritis” over the period of last 3 years.

Results
Mural thickening with luminal stenosis was the most common findings. Aneurysmal dilatation of the descending thoracic aorta was observed in one case. Vessel stenoses without mural thickening, thrombosis and collateral vessel formation were the other findings. Pattern of involvement ranged from variable involvement of thoracic and abdominal aorta and their branches.

Conclusion
Awareness of its CT angiographic appearances and distribution pattern can help the clinicians and radiologists to have high index of suspicion in aiding early diagnosis and better management of this disease.
Russian verbs of motion and their aspectual partners in Fluid Construction Grammar
Authors: Beuls Katrien , Knight Yana , Spranger Michael 
Published: October 2019

Abstract
Russian boasts a highly complex aspectual system which can appear irregular and
difficult to learn. It has recently been suggested that motion verbs, which are
normally seen as exceptional in their nature, may in fact be at the core of this
system, motivating aspectual behavior based on stem directionality. This
suggests that analyzing motion verbs may help understand the Russian aspectual
system as a whole. The present work demonstrates how Russian motion verbs and
their aspectual partners can be implemented and processed successfully with
Fluid Constructional Grammar. The study presents an example of language
processing in both production and comprehension in operation and highlights the
flexibility and power of this formalism, despite the challenges that this
complex aspectual system poses.
At the crossroads between (semi-)free relatives and indirect
questions in French
Authors: Konrad Ingrid 
Published: October 2019

Abstract
In this paper, we examine in some detail the
syntactic properties of (semi-)free relatives in French and their
ambiguity with indirect questions. Based on the results of an
acceptability judgment task, we argue that object free relatives
with a human referent and a full NP subject are ungrammatical in
French. We then focus on free relatives with an inanimate referent
and their ambiguity, often neglected in the literature: the
ce que structure can be either a ‘semi-free
relative clause’ (Rebuschi
2001) or an indirect question. We propose a reanalysis
from ce que to skə, suggesting that ce
que has undergone an incorporation process, parallel
but not identical to the one which has occurred with o
que in Portuguese.
Compression in French
Authors: Destruel Emilie , Féry Caroline 
Published: October 2019

Abstract
This paper sheds light on the conditions for
post-focal and post-verbal compression in French canonical
sentences. We report on a production experiment, which results
suggest that arguments and adjuncts are phrased differently, and
that length and information structure only exert a significant
influence on the realization of adjuncts. We formalize these results
in terms of phrasing, arguing that French, as
opposed to English for instance, does not allow compression at any
prosodic level, but only in syntactically motivated prosodic
phrases. We motivate the variation in our data via optional
phrasing.
Nominal and verbal events in Romance causative
constructions
Authors: Donazzan Marta 
Published: October 2019

Abstract
Romance syntactic causative constructions have
mixed properties that make it difficult to decide about their
monoclausal or biclausal structure (Rizzi 1976, Guasti 1996, a.o.).The aim
of this study is to contribute to the debate by providing an
analysis of these constructions in Italian against the background of
complex predicate formation. I address the issue of the syntactic
category of the complement of fare in syntactic
causatives by comparing them to complex predicates in Italian. I
show that, contrary to what has been claimed in recent analyses,
syntactic causatives are bieventive constructions where the
causative verb embeds a complex clause, and I offer an account of
their surface differences in terms of Voice alternation.
Non-verbal predication and clitics in Aromanian
Authors: Mavrogiorgos Marios , Ledgeway Adam 
Published: October 2019

Abstract
This paper discusses predicational structures in
some Aromanian varieties which involve PP or AP predicates combining
with the copula be. In these structures the internal
argument and subject of be is cross-referenced by an
accusative clitic, as long as it is 3rd person and a topic. However,
Individual-Level APs typically resist cliticisation. We propose that
the clitic is the spell-out of topic and gender/number features
available in Stage-Level predicates only (a spatio-temporal argument
à la Kratzer 1995), with
which the subject agrees, before agreeing with T. We argue that this
structural property captures the restriction to Stage-Level predicate subject topics, the person restriction, and also the fact
that the clitic behaves like a direct object clitic
morphosyntactically.
The relevance of relevance in linguistic analysis
Authors: de Jonge Bob 
Published: October 2019

Abstract
The Spanish simple past tenses (imperfecto and indefinido) are studied
in a literary text, supporting the claim that a discourse-related hypothesis about the meaning of these forms
allows for a correct structural analysis and, moreover, enables a revealing literary analysis. That is, the
meaning hypothesis not only accounts for the overall distribution of these forms in texts but also allows literary
analysts to gather independent evidence for the hypothesis as well as illuminating the interpretations of messages
on a literary level. The meaning hypothesis presented in this paper is based on De Jonge (2000a), which proposes that the indefinido is used for eventualities
under focus and the imperfecto is used for supportive eventualities. The corpus used for the
study was drawn from two short stories by Gabriel García Márquez.
Re-visitando significados
Authors: Martínez Angelita , Mailhes Verónica N. 
Published: October 2019

Resumen
En este trabajo, a partir de los principios de la Escuela Lingüística de Columbia, nos replanteamos la
sustancia semántica que subyace al paradigma que constituyen los llamados Futuro sintético y Futuro perifrástico
en español. Proponemos que dichas formas categorizan el control del emisor sobre la ocurrencia del
evento, mediante la consideración de que el hablante recurre al Futuro perifrástico para
señalar control, y al Futuro sintético para señalar la ausencia de control. A la luz de este
significado del Futuro sintético, la forma resulta adecuada para expresar mensajes tanto de
posibilidad como de profecía. Por otra parte, la opción por la perífrasis se adecua a los mensajes que intentan
inferir control. Probamos nuestra hipótesis sobre el significado de las variantes en un corpus de discurso
periodístico.