bluuebunny/crossref_metadata_2025_split huggingface dataset:
Accumulation of PNPLA3 on lipid droplets is the basis of associated hepatic steatosis
Authors: BasuRay Soumik , Wang Yang , Smagris Eriks , Cohen Jonathan C. , Hobbs Helen H. 
Published: April 2019

Significance
A sequence variant (I148M) in PNPLA3 is a major genetic risk factor for nonalcoholic fatty liver disease. Previously, we showed that PNPLA3(148M) evades ubiquitylation-mediated degradation and accumulates to high levels on lipid droplets (LDs). Here we address how this accumulation is related to steatosis. We generated an active, ubiquitylation-resistant isoform that accumulated on LDs and increased hepatic triglyceride levels when expressed in livers of mice. Conversely, depletion of PNPLA3 resolved the excess hepatic fat accumulation associated with expression of PNPLA3(148M). Our results provide direct evidence that accumulation of PNPLA3 per se causes fatty liver, and that depletion of the protein is a potential strategy for therapeutic intervention.
Radio frequency transmitter based on a laser frequency comb
Authors: Piccardo Marco , Tamagnone Michele , Schwarz Benedikt , Chevalier Paul , Rubin Noah A. , Wang Yongrui , Wang Christine A. , Connors Michael K. , McNulty Daniel , Belyanin Alexey , Capasso Federico 
Published: April 2019

Significance
Semiconductor lasers are compact sources of coherent light. When operating in an optical frequency comb regime, they can generate a spectrum consisting of discrete frequency lines that are equally spaced. Most frequency comb applications, such as spectroscopy and metrology, directly use the optical output of these lasers. In microwave photonics applications, the frequency comb output is sent to a fast photodetector and used to produce microwaves. Here, we propose to integrate laser, detector, and antenna in the same device. We show that, in addition to generating microwaves, a properly designed laser can emit microwaves wirelessly and modulate them with a signal containing information. This work opens the door to a type of hybrid electronic–photonic devices.
Origin of language and origin of languages
Authors: Graffi Giorgio 
Published: April 2019

AbstractThe question of monogenesis vs. polygenesis of human languages was essentially neglected by contemporary linguistics until the appearance of the research on the genetics of human populations by L. L. Cavalli-Sforza and his collaborators, which brought to light very exciting parallels between the distribution of human populations and that of language families. The present paper highlights some aspects of the history of the problem and some points of the contemporary discussion. We first outline the “Biblical paradigm”, which persisted until the 18th century even in scientific milieus. Then, we outline some aspects of the 19th century debate about monogenesis vs. polygenesis of languages and about the relationships between languages and human populations: in particular, we will discuss the views of Darwin on the one hand and of some linguists on the other (Schleicher, M. Müller, Whitney and Trombetti). It will be seen that their positions only partly coincide; at any rate, it will be shown that Darwin was partly inspired by the problems of the genealogy of languages and that the linguists, for their part, took account of Darwin’s views. Turning to today’s debate, we first present the positions of the linguists arguing for monogenesis, namely J. Greenberg and M. Ruhlen, as well as the criticisms raised against their methods by the majority of linguists. Other scholars, such as D. Bickerton or N. Chomsky, essentially argue, from different points of view, that the problem of monogenesis vs. polygenesis of languages is a “pseudo-problem”. We however think that, although the question cannot be reasonably solved by linguistic means, it cannot be discarded as meaningless: it is an anthropological rather than a linguistic problem. We present some reflections and suggestions, in the light of which the monogenetic hypothesis appears as more tenable than the polygenetic one.
The (en)rich(ed) meaning of expletive negation
Authors: Delfitto Denis , Melloni Chiara , Vender Maria 
Published: April 2019

AbstractThis contribution addresses the issue of one of the instances of non-standard negation, the so-called expletive negation (EN). Though it discusses data from a variety of languages, it mainly concentrates on Italian, proposing that the behavior of EN in comparative, exclamative and temporal clauses warrants an analysis of EN in terms of an operator of implicature denial. This approach derives the fact that EN is truth-conditionally irrelevant from the fact that the semantics of negation as a truth-value reversal operator is shifted, in the case of EN, to the layer of implicated meaning. The analysis has a number of interesting consequences for the notion of metalinguistic negation. It further derives many of the interpretive effects normally linked to the so-called evaluative analysis of EN, and is compatible with a new set of data showing that EN scopally interacts with other negative elements. Finally, the proposal advanced here has a number of non-trivial implications regarding the relation between morphosyntax and the systems of interpretation, potentially affecting the standard view of language within cognition.
Inflectional and derivational morphological awareness in Arabic-speaking High versus Low EFL literacy students
Authors: Saiegh-Haddad Elinor , Elouty Arige 
Published: April 2019

Abstract
This paper investigates morphological awareness for inflected and derived words among high versus low literacy
students of English as a foreign language in the 5th, 7th and 9th grades. The study experimented with Arabic L1 students and
tested inflectional morphological awareness (IMA) and derivational morphological awareness (DMA) separately using the Word
Analogy task. Results demonstrate generally less developed morphological awareness skills in low as against high EFL
literacy students. Moreover, significant differences between IMA and DMA in favor on IMA were observed in both groups of students
and across all grades. This appears to reflect the distributional and linguistic properties of the two morphological systems.
Moreover, though morphological awareness emerged rather early in EFL learning, differences between the two morphological systems
decreased, though remained significant, as grade level increased. The theoretical and practical implications of these findings, as
well as the potential role of Arabic as L1, are discussed.
Variation in Perso-Arabic and Devanāgarī Sindhī orthographies
Authors: Iyengar Arvind 
Published: April 2019

AbstractThe Sindhī language has been written in numerous scripts throughout its history. However, in the twentieth century, Perso-Arabic and Devanāgarī emerged as the dominant scripts for the language. Today, Perso-Arabic is the sole official script for Sindhī in Pakistan, while both Perso-Arabic and Devanāgarī are in concurrent use for the language in India. This paper identifies and analyses areas of orthographic standardisation and variation in the Perso-Arabic and Devanāgarī scripts for Sindhī, focusing primarily on practices in the Indian context. It first classifies orthographic variation into that stemming from phonological ambiguity, and that which is purely graphematic. The former includes the representation of reduced vowels, gemination, vocalic endings, loanwords, consonant clusters and sounds of unclear phonemic status. The latter includes the shapes and positioning of diacritics, allographs, derivative graphemes and collation orders. The paper concludes by summarising the possible pedagogical implications of such orthographic standardisation and variation.
Proteomic characterisation of leech microglia extracellular vesicles (EVs): comparison between differential ultracentrifugation and Optiprep™ density gradient isolation
Authors: Arab T , Raffo‐Romero A , Van Camp C , Lemaire Q , Le Marrec‐Croq F , Drago F , Aboulouard S , Slomianny C , Lacoste A‐S , Guigon I , Touzet H , Salzet M , Fournier I , Lefebvre C , Vizioli J , Sautière P‐E 
Published: April 2019

ABSTRACTIn Mammals, microglial cells are considered as the resident immune cells in central nervous system (CNS). Many studies demonstrated that, after injury, these cells are activated and recruited at the lesion site. Leech microglia present a similar pattern of microglial activation and migration upon experimental lesion of CNS. This activation is associated with the release of a large amount of extracellular vesicles (EVs). We collected EVs released by microglia primary culture and compared two different protocols of isolation: one with differential ultracentrifugation (UC) and one using an additional Optiprep™ Density Gradient (ODG) ultracentrifugation. Nanoparticles tracking analysis (NTA) and transmission electron microscopy (TEM) were used to assess vesicles size and morphology. The protein content of isolated EVs was assessed by mass spectrometry approaches. Results showed the presence of EV‐specific proteins in both procedures. The extensive proteomic analysis of each single ODG fractions confirmed the efficiency of this protocol in limiting the presence of co‐isolated proteins aggregates and other membranous particles during vesicles isolation. The present study permitted for the first time the characterisation of microglial EV protein content in an annelid model. Interestingly, an important amount of proteins found in leech vesicles was previously described in EV‐specific databases. Finally, purified EVs were assessed for neurotrophic activity and promote neurites outgrowth on primary cultured neurons.
Constant spacing in filament bundles
Authors: Atkinson Daria W , Santangelo Christian D , Grason Gregory M 
Published: April 2019

Abstract
Assemblies of one-dimensional filaments appear in a wide range of physical systems: from biopolymer bundles, columnar liquid crystals, and superconductor vortex arrays; to familiar macroscopic materials, like ropes, cables, and textiles. Interactions between the constituent filaments in such systems are most sensitive to the distance of closest approach between the central curves which approximate their configuration, subjecting these distinct assemblies to common geometric constraints. In this paper, we consider two distinct notions of constant spacing in multi-filament packings in

R

3

: equidistance, where the distance of closest approach is constant along the length of filament pairs; and isometry, where the distances of closest approach between all neighboring filaments are constant and equal. We show that, although any smooth curve in

R

3

permits one dimensional families of collinear equidistant curves belonging to a ruled surface, there are only two families of tangent fields with mutually equidistant integral curves in

R

3

. The relative shapes and configurations of curves in these families are highly constrained: they must be either (isometric) developable domains, which can bend, but not twist; or (non-isometric) constant-pitch helical bundles, which can twist, but not bend. Thus, filament textures that are simultaneously bent and twisted, such as twisted toroids of condensed DNA plasmids or wire ropes, are doubly frustrated: twist frustrates constant neighbor spacing in the cross-section, while non-equidistance requires additional longitudinal variations of spacing along the filaments. To illustrate the consequences of the failure of equidistance, we compare spacing in three ‘almost equidistant’ ansatzes for twisted toroidal bundles and use our formulation of equidistance to construct upper bounds on the growth of longitudinal variations of spacing with bundle thickness.
A sufficient condition for the finiteness of Frobenius test exponents
Authors: Maddox Kyle 
Published: April 2019

The Frobenius test exponent

Fte
⁡
(
R
)

\operatorname {Fte}(R)

of a local ring

(
R
,

m

)

(R,\mathfrak {m})

of prime characteristic

p
>
0

p>0

is the smallest

e
0

∈

N

e_0 \in \mathbb {N}

such that for every ideal

q

\mathfrak {q}

generated by a (full) system of parameters, the Frobenius closure

q

F

\mathfrak {q}^F

has

(

q

F

)

[

p

e
0

]

=

q

[

p

e
0

]

(\mathfrak {q}^F)^{\left [p^{e_0}\right ]}=\mathfrak {q}^{\left [ p^{e_0}\right ]}

. We establish a sufficient condition for

Fte
⁡
(
R
)
>
∞

\operatorname {Fte}(R)>\infty

and use it to show that if

R
R

is such that the Frobenius closure of the zero submodule in the lower local cohomology modules has finite colength, i.e.,

H

m

j

(
R
)

/

0

H

m

j

(
R
)

F

H^j_\mathfrak {m}(R)/0^F_{H^j_\mathfrak {m}(R)}

is finite length for

0
≤
j
>
dim
⁡
(
R
)

0 \le j > \dim (R)

, then

Fte
⁡
(
R
)
>
∞

\operatorname {Fte}(R)>\infty

.
Two solutions for a planar equation with combined nonlinearities and critical growth
Authors: Furtado Marcelo 
Published: April 2019

We prove the existence of two nonnegative nontrivial solutions for the equation

−
Δ
u
−

1
2

(
x
⋅
∇
u
)
=
λ
a
(
x
)

|

u

|

q
−
2

u
+
f
(
u
)
,

x
∈

R

2

,

\begin{equation*} -\Delta u -\frac {1}{2} (x\cdot \nabla u) = \lambda a(x)|u|^{q-2}u+f(u),\qquad x\in \mathbb {R}^2, \end{equation*}

where

1
>
q
>
2

1>q>2

,

a
a

is indefinite in sign, and the function

f
(
s
)

f(s)

behaves like

e

α

s
2

e^{\alpha s^2}

at infinity. The results hold for small values of the parameter

λ
>
0

\lambda >0

.
Using the Self-Controlled Tree-Temporal Scan Statistic to Assess the Safety of Live Attenuated Herpes Zoster Vaccine
Authors: Yih W Katherine , Kulldorff Martin , Dashevsky Inna , Maro Judith C 
Published: April 2019

Abstract
The self-controlled tree-temporal scan statistic allows detection of potential vaccine- or drug-associated adverse events without prespecifying the specific events or postexposure risk intervals of concern. It thus opens a promising new avenue for safety studies. The method has been successfully used to evaluate the safety of 2 vaccines for adolescents and young adults, but its suitability to study vaccines for older adults had not been established. The present study applied the method to assess the safety of live attenuated herpes zoster vaccination during 2011–2017 in US adults aged ≥60 years, using claims data from Truven Health MarketScan Research Databases. Counts of International Classification of Diseases diagnosis codes recorded in emergency department or hospital settings were scanned for any statistically unusual clustering within a hierarchical tree structure of diagnoses and within 42 days after vaccination. Among 1.24 million vaccinations, 4 clusters were found: cellulitis on days 1–3, nonspecific erythematous condition on days 2–4, “other complications . . .” on days 1–3, and nonspecific allergy on days 1–6. These results are consistent with local injection-site reactions and other known, generally mild, vaccine-associated adverse events and a favorable safety profile. This method might be useful for assessing the safety of other vaccines for older adults.
Insights from the study of complex systems for the ecology and evolution of animal populations
Authors: Fisher David N , Pruitt Jonathan N 
Published: April 2019

AbstractPopulations of animals comprise many individuals, interacting in multiple contexts, and displaying heterogeneous behaviors. The interactions among individuals can often create population dynamics that are fundamentally deterministic yet display unpredictable dynamics. Animal populations can, therefore, be thought of as complex systems. Complex systems display properties such as nonlinearity and uncertainty and show emergent properties that cannot be explained by a simple sum of the interacting components. Any system where entities compete, cooperate, or interfere with one another may possess such qualities, making animal populations similar on many levels to complex systems. Some fields are already embracing elements of complexity to help understand the dynamics of animal populations, but a wider application of complexity science in ecology and evolution has not occurred. We review here how approaches from complexity science could be applied to the study of the interactions and behavior of individuals within animal populations and highlight how this way of thinking can enhance our understanding of population dynamics in animals. We focus on 8 key characteristics of complex systems: hierarchy, heterogeneity, self-organization, openness, adaptation, memory, nonlinearity, and uncertainty. For each topic we discuss how concepts from complexity theory are applicable in animal populations and emphasize the unique insights they provide. We finish by outlining outstanding questions or predictions to be evaluated using behavioral and ecological data. Our goal throughout this article is to familiarize animal ecologists with the basics of each of these concepts and highlight the new perspectives that they could bring to variety of subfields.
Pathogenic budding yeasts isolated outside of clinical settings
Authors: Opulente Dana A , Langdon Quinn K , Buh Kelly V , Haase Max A B , Sylvester Kayla , Moriarty Ryan V , Jarzyna Martin , Considine Samantha L , Schneider Rachel M , Hittinger Chris Todd 
Published: April 2019

ABSTRACT
Budding yeasts are distributed across a wide range of habitats, including as human commensals. However, under some conditions, these commensals can cause superficial, invasive, and even lethal infections. Despite their importance to human health, little is known about the ecology of these opportunistic pathogens, aside from their associations with mammals and clinical environments. During a survey of approximately 1000 non-clinical samples across the United States of America, we isolated 54 strains of budding yeast species considered opportunistic pathogens, including Candida albicans and Candida (Nakaseomyces) glabrata. We found that, as a group, pathogenic yeasts were positively associated with fruits and soil environments, whereas the species Pichia kudriavzevii (syn. Candida krusei syn. Issatchenkia orientalis) had a significant association with plants. Of the four species that cause 95% of candidiasis, we found a positive association with soil. These results suggest that pathogenic yeast ecology is more complex and diverse than is currently appreciated and raises the possibility that these additional environments could be a point of contact for human infections.
Standard-Dose Intradermal Influenza Vaccine Elicits Cellular Immune Responses Similar to Those of Intramuscular Vaccine in Men With and Those Without HIV Infection
Authors: Amoah Samuel , Mishina Margarita , Praphasiri Prabda , Cao Weiping , Kim Jin Hyang , Liepkalns Justine S , Guo Zhu , Carney Paul J , Chang Jessie C , Fernandez Stefan , Garg Shikha , Beacham Lauren , Holtz Timothy H , Curlin Marcel E , Dawood Fatimah , Olsen Sonja J , Gangappa Shivaprakash , Stevens James , Sambhara Suryaprakash 
Published: April 2019

Abstract

Background
Human immunodeficiency virus (HIV)–infected persons are at a higher risk of severe influenza. Although we have shown that a standard-dose intradermal influenza vaccine versus a standard-dose intramuscular influenza vaccine does not result in differences in hemagglutination-inhibition titers in this population, a comprehensive examination of cell-mediated immune responses remains lacking.

Methods
Serological, antigen-specific B-cell, and interleukin 2–, interferon γ–, and tumor necrosis factor α–secreting T-cell responses were assessed in 79 HIV-infected men and 79 HIV-uninfected men.

Results
The route of vaccination did not affect the immunoglobulin A and immunoglobulin G (IgG) plasmablast or memory B-cell response, although these were severely impaired in the group with a CD4+ T-cell count of <200 cells/μL. The frequencies of IgG memory B cells measured on day 28 after vaccination were highest in the HIV-uninfected group, followed by the group with a CD4+ T-cell count of ≥200 cells/μL and the group with a CD4+ T-cell count of <200 cells/μL. The route of vaccination did not affect the CD4+ or CD8+ T-cell responses measured at various times after vaccination.

Conclusions
The route of vaccination had no effect on antibody responses, antibody avidity, T-cell responses, or B-cell responses in HIV-infected or HIV-uninfected subjects. With the serological and cellular immune responses to influenza vaccination being impaired in HIV-infected individuals with a CD4+ T-cell count of <200 cells/μL, passive immunization strategies need to be explored to protect this population.

Clinical trials registration
NCT01538940.
Pathomechanisms of immune-mediated alopecia
Authors: Anzai Alessandra , Wang Eddy Hsi Chun , Lee Eunice Y , Aoki Valeria , Christiano Angela M 
Published: April 2019

Abstract
The hair follicle (HF) is a complex mini-organ that constantly undergoes dynamic cycles of growth and regression throughout life. While proper progression of the hair cycle requires homeostatic interplay between the HF and its immune microenvironment, specific parts of the HF, such as the bulge throughout the hair cycle and the bulb in the anagen phase, maintain relative immune privilege (IP). When this IP collapses, inflammatory infiltrates that aggregate around the bulge and bulb launch an immune attack on the HF, resulting in hair loss or alopecia. Alopecia areata (AA) and primary cicatricial alopecia (PCA) are two common forms of immune-mediated alopecias, and recent advancements in understanding their disease mechanisms have accelerated the discovery of novel treatments for immune-mediated alopecias, specifically AA. In this review, we highlight the pathomechanisms involved in both AA and CA in hopes that a deeper understanding of their underlying disease pathogenesis will encourage the development of more effective treatments that can target distinct disease pathways with greater specificity while minimizing adverse effects.
Genetic variation and relationships among Afrotropical species of Myotis (Chiroptera: Vespertilionidae)
Authors: Patterson Bruce D , Webala Paul W , Kerbis Peterhans Julian C , Goodman Steven M , Bartonjo Michael , Demos Terrence C 
Published: April 2019

Abstract
The genus Myotis is nearly cosmopolitan and the second-most speciose genus of mammals, but its Afrotropical members are few and poorly known. We analyzed phylogenetic and phylogeographic relationships of six of the eight known Afrotropical species using Cytb and sequences from four nuclear introns. Using Bayesian and maximum-likelihood approaches to generate single-locus, concatenated, and species trees, we confirmed prior evidence that the clade containing Afrotropical Myotis also contains both Palearctic and Indomalayan members. Additionally, we demonstrate that M. bocagii is sister to the Indian Ocean species M. anjouanensis, that this group is sister to M. tricolor and the Palearctic M. emarginatus, and find evidence suggesting that M. welwitschii is the earliest-diverging Afrotropical species and sister to the remainder. Although M. tricolor and M. welwitschii are both currently regarded as monotypic, both mitochondrial and nuclear data sets document significant, largely concordant geographic structure in each. Evidence for the distinction of two lineages within M. tricolor is particularly strong. On the other hand, geographic structure is lacking in M. bocagii, despite the current recognition of two subspecies in that species. Additional geographic sampling (especially at or near type localities), finer-scale sampling (especially in zones of sympatry), and integrative taxonomic assessments will be needed to better document this radiation and refine its nomenclature.