bluuebunny/crossref_metadata_2025_split huggingface dataset:
Homoarginine and inhibition of human arginase activity: kinetic characterization and biological relevance
Authors: Tommasi S. , Elliot D. J. , Da Boit M. , Gray S. R. , Lewis B. C. , Mangoni A. A. 
Published: February 2018

AbstractThe inhibition of arginase, resulting in higher arginine (ARG) availability for nitric oxide synthesis, may account for the putative protective effect of homoarginine (HOMOARG) against atherosclerosis and cardiovascular disease. However, uncertainty exists regarding the significance of HOMOARG-induced arginase inhibition in vivo. A novel UPLC-MS method, measuring the conversion of ARG to ornithine (ORN), was developed to determine arginase 1 and arginase 2 inhibition by HOMOARG, lysine (LYS), proline (PRO), agmatine (AG), asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), and NG-Monomethyl-L-arginine (L-NMMA). Plasma HOMOARG, ARG and ORN concentrations were further measured in 50 healthy older adults >65 years (27 males and 23 females). HOMOARG inhibited arginase 1 with IC50 and Ki values of 8.14 ± 0.52 mM and 6.1 ± 0.50 mM, and arginase 2 with IC50 and Ki values of 2.52 ± 0.01 mM and 1.73 ± 0.10 mM, respectively. Both arginase isoforms retained 90% activity vs. control when physiological HOMOARG concentrations (1–10 µM) were used. In partial correlation analysis, plasma HOMOARG was not associated with ARG (P = 0.38) or ARG/ORN ratio (P = 0.73) in older adults. Our results suggest that arginase inhibition is unlikely to play a significant role in the reported cardio-protective effects of HOMOARG.
Chimeric peptide EP45 as a dual agonist at GLP-1 and NPY2R receptors
Authors: Chepurny Oleg G. , Bonaccorso Ron L. , Leech Colin A. , Wöllert Torsten , Langford George M. , Schwede Frank , Roth Christian L. , Doyle Robert P. , Holz George G. 
Published: February 2018

AbstractWe report the design and target validation of chimeric peptide EP45, a novel 45 amino acid monomeric dual agonist peptide that contains amino acid sequence motifs present within the blood glucose-lowering agent exendin-4 (Ex-4) and the appetite-suppressing agent PYY(3–36). In a new high-throughput FRET assay that provides real-time kinetic information concerning levels of cAMP in living cells, EP45 recapitulates the action of Ex-4 to stimulate cAMP production via the glucagon-like peptide-1 receptor (GLP-1R), while also recapitulating the action of PYY(3–36) to inhibit cAMP production via the neuropeptide Y2receptor (NPY2R). EP45 fails to activate glucagon or GIP receptors, whereas for cells that co-express NPY2R and adenosine A2Breceptors, EP45 acts in an NPY2R-mediated manner to suppress stimulatory effects of adenosine on cAMP production. Collectively, such findings are remarkable in that they suggest a new strategy in which the co-existing metabolic disorders of type 2 diabetes and obesity will be treatable using a single peptide such as EP45 that lowers levels of blood glucose by virtue of its GLP-1R-mediated effect, while simultaneously suppressing appetite by virtue of its NPY2R-mediated effect.
Genetic heterogeneity of primary lesion and metastasis in small intestine neuroendocrine tumors
Authors: Walter Dirk , Harter Patrick N. , Battke Florian , Winkelmann Ria , Schneider Markus , Holzer Katharina , Koch Christine , Bojunga Jörg , Zeuzem Stefan , Hansmann Martin Leo , Peveling-Oberhag Jan , Waidmann Oliver 
Published: February 2018

AbstractData on intratumoral heterogeneity of small intestine neuroendocrine tumors (SI-NETs) and related liver metastasis are limited. The aim of this study was to characterize genetic heterogeneity of 5 patients with SI-NETs. Therefore, formalin-fixed, paraffin-embedded tissue samples of primary and metastatic lesions as well as benign liver of five patients with synchronously metastasized, well differentiated SI-NETs were analyzed with whole exome sequencing. For one patient, chip based 850k whole DNA methylome analysis was performed of primary and metastatic tumor tissue as well as control tissue. Thereby, 156 single nucleotide variants (SNVs) in 150 genes were identified and amount of mutations per sample ranged from 9–34 (mean 22). The degree of common (0–94%) and private mutations per sample was strongly varying (6–100%). In all patients, copy number variations (CNV) were found and the degree of intratumoral heterogeneity of CNVs corresponded to SNV analysis. DNA methylation analysis of a patient without common SNVs revealed a large overlap of common methylated CpG sites. In conclusion, SI-NET primary and metastatic lesions show a highly varying degree of intratumoral heterogeneity. Driver events might not be detectable with exome analysis only, and further comprehensive studies including whole genome and epigenetic analyses are warranted.
Nestedness patterns and the role of morphodynamics and spatial distance on sandy beach fauna: ecological hypotheses and conservation strategies
Authors: Checon Helio H. , Corte Guilherme N. , Shah Esmaeili Yasmina M. L. , Amaral A. Cecilia Z. 
Published: February 2018

AbstractSandy beach fauna is hypothesized to be mainly structured by environmental variables. As such, it is expected that morphodynamic characteristics are limiting factors, and the species pool inhabiting harsher reflective beaches would be a subset of (i.e., nested in) the fauna of nearby dissipative beaches. We investigated the existence of a nestedness pattern in sandy beach assemblages, as well as the contribution of environmental and spatial variables (i.e., factors that potentially affect an assemblage regardless of environmental conditions - typically related to distance between sites and dispersal of organisms) on sandy beach macrobenthic fauna. Dissipative beaches had higher species richness than reflective beaches but we found no nestedness pattern. Furthermore, almost every beach showed exclusive species. Spatial variables exerted stronger influence on macrobenthic assemblages than local environmental variables. Our results therefore suggest that local and small-scale recruitment is the predominant process structuring macrobenthic assemblages. These results bring important implications for sandy beach conservation: given that spatial distance is an important factor structuring macrobenthic fauna and different sandy beaches harbor different pools of species, conservation programs need to focus on sandy beaches across large spatial scales and with varied morphodynamic characteristics in order to preserve coastal biodiversity.
Target delivery of doxorubicin tethered with PVP stabilized gold nanoparticles for effective treatment of lung cancer
Authors: Ramalingam Vaikundamoorthy , Varunkumar Krishnamoorthy , Ravikumar Vilwanathan , Rajaram Rajendran 
Published: February 2018

AbstractDevelopment of drug delivery system conjugated with doxorubicin (dox) on the surface of AuNPs with polyvinylpyrrolidone (Dox@PVP-AuNPs), we have demonstrated that human lung cancer cells can significantly overcome by the combination of highly effective cellular entry and responsive intracellular release of doxorubicin from Dox@PVP-AuNPs complex. Previously drug release from doxorubicin-conjugated AuNPs was confirmed by the recovered fluorescence of doxorubicin from quenching due to the nanosurface energy transfer between doxorubicinyl groups and AuNPs. Dox@PVP-AuNPs achieved enhanced inhibition of lung cancer cells growth than free Doxorubicin and PVP-AuNPs. The in vitro cytotoxic effect of PVP-AuNPs, free Dox and Dox@PVP-AuNPs inhibited the proliferation of human lung cancer cells with IC50 concentration. Compared with control cells, PVP-AuNPs and free Dox, Dox@PVP-AuNPs can increases ROS generation, sensitize mitochondrial membrane potential and induces both early and late apoptosis in lung cancer cells. Moreover, Dox@PVP-AuNPs highly upregulates the expression of tumor suppressor genes than free Dox and PVP-AuNPs and induces intrinsic apoptosis in lung cancer cells. From the results, Dox@PVP-AuNPs can be considered as an potential drug delivery system for effective treatment of human lung cancer.
TRPV4-mediates oscillatory fluid shear mechanotransduction in mesenchymal stem cells in part via the primary cilium
Authors: Corrigan Michele A. , Johnson Gillian P. , Stavenschi Elena , Riffault Mathieu , Labour Marie-Noelle , Hoey David A. 
Published: February 2018

AbstractSkeletal homeostasis requires the continued replenishment of the bone forming osteoblast from a mesenchymal stem cell (MSC) population, a process that has been shown to be mechanically regulated. However, the mechanisms by which a biophysical stimulus can induce a change in biochemical signaling, mechanotransduction, is poorly understood. As a precursor to loading-induced bone formation, deciphering the molecular mechanisms of MSC osteogenesis is a critical step in developing novel anabolic therapies. Therefore, in this study we characterize the expression of the mechanosensitive calcium channel Transient Receptor Potential subfamily V member 4 (TRPV4) in MSCs and demonstrate that TRPV4 localizes to areas of high strain, specifically the primary cilium. We demonstrate that TRPV4 is required for MSC mechanotransduction, mediating oscillatory fluid shear induced calcium signaling and early osteogenic gene expression. Furthermore, we demonstrate that TRPV4 can be activated pharmacologically eliciting a response that mirrors that seen with mechanical stimulation. Lastly, we show that TRPV4 localization to the primary cilium is functionally significant, with MSCs with defective primary cilia exhibiting an inhibited osteogenic response to TRPV4 activation. Collectively, this data demonstrates a novel mechanism of stem cell mechanotransduction, which can be targeted therapeutically, and further highlights the critical role of the primary cilium in MSC biology.
Collision sensitive niche profile of the worst affected bird-groups at wind turbine structures in the Federal State of Brandenburg, Germany
Authors: Bose Anushika , Dürr Tobias , Klenke Reinhard A. , Henle Klaus 
Published: February 2018

AbstractBiodiversity-related impacts at wind energy facilities have increasingly become a cause of conservation concern, central issue being the collision of birds. Utilizing spatial information of their carcass detections at wind turbines (WTs), we quantified the detections in relation to the metric distances of the respective turbines to different land-use types. We used ecological niche factor analysis (ENFA) to identify combinations of land-use distances with respect to the spatial allocation of WTs that led to higher proportions of collisions among the worst affected bird-groups: Buntings, Crows, Larks, Pigeons and Raptors. We also assessed their respective similarities to the collision phenomenon by checking for overlaps amongst their distance combinations. Crows and Larks showed the narrowest “collision sensitive niche”; a part of ecological niche under higher risk of collisions with turbines, followed by that of Buntings and Pigeons. Raptors had the broadest niche showing significant overlaps with the collision sensitive niches of the other groups. This can probably be attributed to their larger home range combined with their hunting affinities to open landscapes. Identification of collision sensitive niches could be a powerful tool for landscape planning; helping avoid regions with higher risks of collisions for turbine allocations and thus protecting sensitive bird populations.
Nail or plate in the management of distal extra-articular tibial fracture, what is better? Valutation of outcomes
Authors: Bisaccia Michele , Cappiello Andrea , Meccariello Luigi , Rinonapoli Giuseppe , Falzarano Gabriele , Medici Antonio , Vicente Cristina Ibáñez , Piscitelli Luigi , Stano Verdiana , Bisaccia Olga , Caraffa Auro 
Published: February 2018

Introduction: Distal tibial fractures are the most common long bone fractures. Several studies focusing on the methods of treatment of displaced distal tibial fractures have been published. To date, locked plates, intramedullary nails and external fixation are the three most used techniques. The aim of our study was to compare intramedullary nail (IMN) and locked plate (LP) for treatment of this kind of fracture.
Materials and methods: We collected data on 81 patients with distal tibial fractures (distance from the joint between 40 and 100 mm) and we divided into two groups: IMN and LP. We compared in the 2 groups the mean operation time, the mean union time, the infection rate the rate of malunion and nonunion, the full weight bearing time.
Results: No patient in the two groups developed a nonunion. None of the patients obtained a fair or poor outcome. Overall 52 patients obtained an excellent result (69.3%) and 23 obtained a good result (30.6%).
Discussion: Our study results indicate a superiority of IMN over LP in terms of lower rates of infections and statistically significant shorter time to full weight bearing. Whereas LP appeared to be advantageous over IMN in terms of leading to a better anatomical and fixed reductions of the fracture and a lower rate of union complications. The two treatments achieved comparable results in terms of operation time, hospital stay, union time and functional outcomes.
Thorakolumbale Frakturen – Fixateur perkutan
Authors: Blattert Thomas , Katscher Sebastian 
Published: February 2018

ZusammenfassungWährend Reposition und Stabilisierung von thorakolumbalen Wirbelfrakturen lange Zeit eine Domäne des offenen Vorgehens waren, haben sich perkutane Techniken zwischenzeitlich umfangreich etabliert. Neben den schon seit jeher klassischen MIS-Indikationen der temporären internen Stabilisierung wie zum Beispiel bei der ossären Chance-Verletzung, sind die Vorteile des minimalinvasiven Vorgehens mit ihrem weichteilschonenden Charakter zwischenzeitlich evidenzbasiert nachgewiesen. Dies hat zu einer deutlichen Erweiterung des Indikationsspektrums geführt, wie die Verwendung perkutaner Verfahren in der Alterstraumatologie oder der Initialstabilisierung polytraumatisierter Wirbelsäulenverletzter. War die Repositionsqualität früherer perkutaner Systeme bisweilen kompromissbehaftet, so haben sich die Implantate mittlerweile wesentlich weiterentwickelt und können unter Verwendung entsprechender externer Repositionshilfen nun eine den offenen Verfahren ebenbürtige Reposition erreichen. Zudem wurden minimalinvasive Dekompressionstechniken entwickelt, so dass auch die Notwendigkeit einer neben der Stabilisierung zusätzlichen Dekompression kein Grund zur Konversion mehr ist. Einer der wesentlichen Nachteile der perkutanen Insertion von Pedikelschrauben-Stab-Systemen gegenüber dem offenen Vorgehen ist die erhöhte Strahlenbelastung des OP-Personals. Dies lässt sich jedoch durch zusätzliche Verwendung intraoperativer Navigationssysteme deutlich relativieren.
Nicht kleinzelliges Lungenkarzinom – doppelte Resistenzentwicklung
Authors: Moeller M. , Siebolts U. , Wickenhauser C. , Schuette W. 
Published: February 2018

ZusammenfassungErworbene Resistenzen gegenüber Tyrosinkinaseinhibitoren beim nicht kleinzelligen Lungenkarzinom entwickeln sich nach etwa 9 – 12 Monaten. In etwa 60 % der Fälle entstehen diese durch eine sekundäre EGFR-T790 M Resistenzmutation. In dieser Kasuistik wird der Fall einer Patientin mit einer Mutation im EGFR Exon 19 beschrieben. Es entwickeln sich unter TKI-Therapie 2 parallele Resistenzmechanismen. Zum einen eine T790M-Resistenzmutation, zum anderen die Transformation in ein kleinzelliges neuroendokrines Karzinom. Unter der Therapie mit Osimertinib sowie paralleler Chemotherapie mit Carboplatin und Etoposid konnte nach 2 Zyklen eine partielle Remission erzielt werden.
Comparing the representation of refugees, asylum seekers and migrants in the Irish and UK press
Authors: O’Regan Veronica , Riordan Elaine 
Published: February 2018

Abstract
Coverage of migration in the media intensified during 2015 against the backdrop of a largescale European refugee crisis. Using corpus linguistics and critical discourse analysis, we explore the representation of refugees, asylum seekers, immigrants and migrants from September to November 2015, in UK and Irish newspapers. Data was collected from Nexis, using the Baker et al. (2008) RASIM framework. Using corpus linguistic techniques, we identify how these groups are represented, before drawing on CDA to examine the data sets further. Frequency lists of the UK and Irish corpora were compared across variety followed by more detailed diachronic analysis of the most frequently occurring items. The extent to which the issue of migration is refracted through a discourse of terrorism in Irish and UK coverage is compared through cluster analyses and a close CDA analysis of randomised downsamples of the Irish and UK sub-corpora drawing in particular on the DHA approach.
At the boundaries of linguistic convergence: Variation in presentational haber / haver-hi
Authors: Blas Arroyo José Luis 
Published: February 2018

Abstract
In this paper, we focus on an eventual convergence outcome (the pluralization of presentational haber/haver-hi) in the grammar of two Romance languages, Spanish and Catalan, which have been living side-by-side for centuries in Eastern Spain. Taking into account the sociolinguistic comparative method and on the basis of several representative corpora of the two languages in contact, the data from this research offer evidence that points to a notable congruence between the underlying grammars of both languages, which would, at least partially, account for a similar diffusion of these vernacular pluralizations. Moreover, some of the few cases of disagreement found can be explained on the basis of both internal (such as the existence of points of structural conflict in some verbal paradigms) and external factors (such as hypercorrection), which certain social groups particularly sensitive to normative pressure are more receptive to.
‘Exclamative’ and ‘quotative’ illocutionary complementisers in Catalan, European Portuguese and Spanish
Authors: Corr Alice 
Published: February 2018

AbstractThe use of the Ibero-Romance complementiserquein non-embedded contexts with various illocutionary functions is argued to be non-trivially distinct from its canonical function as a marker of subordination. Interpretative and grammatical differences, and variation in the availability and clause-typing of non-embedded ‘exclamative’ and ‘quotative’ illocutionaryqueacross Catalan, European Portuguese and Spanish provide evidence that the subordinating complementiser has been repurposed for the representation of pragmatic information in the complementiser systems of Ibero-Romance, a hypothesis supported by analogies drawn between illocutionaryqueand illocutionary functions of the interrogative complementisersi/sein Catalan and European Portuguese.
Public service reforms and clientelism: explaining variation of service delivery modes in Croatian social policy
Authors: Kekez Anka 
Published: February 2018

Abstract
This article seeks to explain the differences in outcomes of social services reform in Croatia during the previous two decades. While the service management reform was based on the principles of effectiveness, efficiency and participation in one segment of social services, in the other segment, reform was used for the development of partisan patronage networks. Using the comparable case strategy, the article focuses on six social services and relies on interviews with policy actors and official documents to map and explain different reform outcomes. The article identifies two factors that led to differences in provision of reformed social services and affected the capacity of the patronage-driven political executive to use reform as an instrument of politicized allocation of public jobs. A sufficiently institutionalized setting in which services were provided prior to the reform reduces the ability of political parties to integrate political patronage into service management. In the case of minimal or non-existent institutional setting, the presence of empowered or represented beneficiaries acts as the bulwark against political capture.
Abelian spiders and real cyclotomic integers
Authors: Calegari Frank , Guo Zoey 
Published: February 2018

If

Γ
\Gamma

is a finite graph, then the largest eigenvalue

λ
\lambda

of the adjacency matrix of

Γ
\Gamma

is a totally real algebraic integer (

λ
\lambda

is the Perron-Frobenius eigenvalue of

Γ
\Gamma

). We say that

Γ
\Gamma

is abelian if the field generated by

λ
2

\lambda ^2

is abelian. Given a fixed graph

Γ
\Gamma

and a fixed set of vertices of

Γ
\Gamma

, we define a spider graph to be a graph obtained by attaching to each of the chosen vertices of

Γ
\Gamma

some

2
2

-valent trees of finite length. The main result is that only finitely many of the corresponding spider graphs are both abelian and not Dynkin diagrams, and that all such spiders can be effectively enumerated; this generalizes a previous result of Calegari, Morrison, and Snyder. The main theorem has applications to the classification of finite index subfactors. We also prove that the set of Salem numbers of “abelian type” is discrete.
Topology of the Grünbaum–Hadwiger–Ramos hyperplane mass partition problem
Authors: Blagojević Pavle , Frick Florian , Haase Albert , Ziegler Günter 
Published: February 2018

In 1960 Grünbaum asked whether for any finite mass inRd\mathbb {R}^dthere areddhyperplanes that cut it into2d2^dequal parts. This was proved by Hadwiger (1966) ford≤3d\le 3, but disproved by Avis (1984) ford≥5d\ge 5, while the cased=4d=4remained open.

More generally, Ramos (1996) asked for the smallest dimensionΔ(j,k)\Delta (j,k)in which for anyjjmasses there arekkaffine hyperplanes that simultaneously cut each of the masses into2k2^kequal parts. At present the best lower bounds onΔ(j,k)\Delta (j,k)are provided by Avis (1984) and Ramos (1996), the best upper bounds by Mani-Levitska, Vrećica and Živaljević (2006). The problem has been an active testing ground for advanced machinery from equivariant topology.

We give a critical review of the work on the Grünbaum–Hadwiger–Ramos problem, which includes the documentation of essential gaps in the proofs for some previous claims. Furthermore, we establish thatΔ(j,2)=12(3j+1)\Delta (j,2)= \frac 12(3j+1)in the cases whenj−1j-1is a power of 22,j≥5j\ge 5.
Spatial asymptotics at infinity for heat kernels of integro-differential operators
Authors: Kaleta Kamil , Sztonyk Paweł 
Published: February 2018

We study a spatial asymptotic behavior at infinity of kernels

p
t

(
x
)

p_t(x)

for convolution semigroups of nonlocal pseudo-differential operators. We give general and sharp sufficient conditions under which the limits

lim

r
→
∞

p
t

(
r
θ
−
y
)

t

ν
(
r
θ
)

,

t
∈
T
,

θ
∈
E
,

y
∈

R

d

\begin{equation*} \lim _{r \to \infty } \frac {p_t(r\theta -y)}{t \, \nu (r\theta )}, \quad t \in T, \ \ \theta \in E, \ \ y \in \mathbb {R}^d \end{equation*}

exist and can be effectively computed. Here

ν
\nu

is the corresponding Lévy density,

T
⊂
(
0
,
∞
)

T \subset (0,\infty )

is a bounded time-set, and

E
E

is a subset of the unit sphere in

R

d

\mathbb {R}^d

,

d
≥
1

d \geq 1

. Our results are local on the unit sphere. They apply to a wide class of convolution semigroups, including those corresponding to highly asymmetric (finite and infinite) Lévy measures. Key examples include fairly general families of stable, tempered stable, jump-diffusion, and compound Poisson semigroups. A main emphasis is put on the semigroups with Lévy measures that are exponentially localized at infinity, for which our assumptions and results are strongly related to the existence of the multidimensional exponential moments. Here a key example is the evolution semigroup corresponding to the so-called quasi-relativistic Hamiltonian

−
Δ
+

m
2

−
m

\sqrt {-\Delta +m^2} - m

,

m
>
0

m>0

. As a byproduct, we also obtain sharp two-sided estimates of the kernels

p
t

p_t

in generalized cones, away from the origin.