bluuebunny/crossref_metadata_2025_split huggingface dataset:
Skilled migration and economic performances: Evidence from OECD countries
Authors: Orefice Gianluca 
Published: January 2018

Summary
This paper investigates the effects of immigration flows and their human capital content on per capita GDP variation in 24 OECD host countries. Theoretical models concludes that the effect of immigrants in host country’s income depends on the human capital content of migrants (Benhabib, 1996); empirically the question is still open and this paper contributes to make light on this. So we propose an empirical estimation on the effects of immigrants and their human capital content on per capita GDP variation. Using a IV model to solve the endogeneity problem we found that high human capital content by immigrants has a positive effect on per capita GDP variation, but it is not enough to fully compensate the overall negative effects of migration on changes in per capita output.
Overall Survival of Papillary Thyroid Carcinoma Patients: A Single‐Institution Long‐Term Follow‐Up of 5897 Patients
Authors: Ito Yasuhiro , Miyauchi Akira , Kihara Minoru , Fukushima Mitsuhiro , Higashiyama Takuya , Miya Akihiro 
Published: January 2018

AbstractIntroductionPapillary thyroid carcinoma (PTC) generally shows an excellent prognosis except in cases with aggressive backgrounds or clinicopathological features. Although the cause‐specific survival (CSS) of PTC patients has been extensively investigated, the overall survival (OS) of these patients is unclear. We herein investigated both the OS and CSS of a large PTC patient series.Materials and methodsWe enrolled 5897 PTC patients who underwent initial surgery between 1987 and 2005 (658 males and 5339 females; median age 51 years). Their median postoperative follow‐up period was 177 months. Univariate and multivariate analyses for OS and CSS assessed the effects of gender, older age (≥55 years), distant metastasis at diagnosis (M1), significant extrathyroid extension, tumor size (cutoffs 2 and 4 cm), large node metastasis (N ≥ 3 cm), and extranodal tumor extension.ResultsTo date, 387 patients (7%) in this series have died from various causes, including 117 (2%) due to PTC. The 10‐, 15‐, and 20‐year OS rates are 97, 95, and 90%, respectively. Older age and M1 were important prognostic factors for OS and CSS. Older age was a more significant factor than M1 for OS and vice versa for CSS. In the older patients, M1 was a prominent prognostic factor for both OS and CSS. In the young patients, M1 had less prognostic impact than in the older patients, and the prognostic values of M1 and N ≥ 3 cm for OS and CSS were identical and similar, respectively.ConclusionsThe most important prognostic value for OS was patient age, indicating that PTC is generally indolent. However, the control of distant metastasis in older patients remains a future challenge in order to further improve their OS and CSS. PTC of ≥3 cm in young patients should be carefully followed, even in the absence of metastases, and these patients should undergo aggressive therapies for recurrent lesions and metastases.
Risk of progression from subjective cognitive decline to mild cognitive impairment: The role of study setting
Authors: Snitz Beth E. , Wang Tianxiu , Cloonan Yona Keich , Jacobsen Erin , Chang Chung‐Chou H. , Hughes Tiffany F. , Kamboh M. Ilyas , Ganguli Mary 
Published: January 2018

AbstractIntroductionWe compared risk of progression from subjective cognitive decline (SCD) to mild cognitive impairment (MCI) in an academic memory clinic versus a population‐based study.MethodsOlder adults presenting at a memory clinic were classified as SCD (n = 113) or as noncomplainers (n = 82). Participants from a population study were classified as SCD (n = 592) and noncomplainers (n = 589) based on a memory complaint score. Annual follow‐up performed for a mean of 3 years.ResultsThe adjusted hazard ratio for SCD was 15.97 (95% confidence interval: 6.08–42.02, P < .001) in the memory clinic versus 1.18 (95% confidence interval: 1.00–1.40, P = .047) in the population study, where reported “worry” about memory further increased SCD‐associated risk for MCI.DiscussionSCD is more likely to progress to MCI in a memory clinic than the general population; participants' characteristics vary across settings. Study setting should be considered when evaluating SCD as a risk state for MCI and dementia.
Translational inhibition of APP by Posiphen: Efficacy, pharmacodynamics, and pharmacokinetics in the APP/PS1 mouse
Authors: Teich Andrew F. , Sharma Ekta , Barnwell Eliza , Zhang Hong , Staniszewski Agnieszka , Utsuki Tadanobu , Padmaraju Vasudevaraju , Mazell Cheryl , Tzekou Apostolia , Sambamurti Kumar , Arancio Ottavio , Maccecchini Maria L. 
Published: January 2018

AbstractIntroductionTranslational inhibition of amyloid precursor protein (APP) by Posiphen has been shown to reduce APP and its fragments in cell culture, animal models, and mildly cognitively impaired patients, making it a promising drug candidate for the treatment of Alzheimer's disease.MethodsWe used a mouse model of Alzheimer's disease (APP/presenilin‐1) to examine Posiphen's efficacy, pharmacodynamics, and pharmacokinetics.ResultsPosiphen treatment normalized impairments in spatial working memory, contextual fear learning, and synaptic function in APP/presenilin‐1 mice, without affecting their visual acuity, motor skills, or motivation and without affecting wild‐type mice. Posiphen had a prolonged effect in reducing APP and all related peptides for at least 9 hours after the last dose. Its concentration was higher in the brain than in plasma, and the most abundant metabolite was N8‐norPosiphen.DiscussionThis is the first study demonstrating the therapeutic efficacy of inhibiting the translation of APP and its fragments in an Alzheimer's disease model.
Rationally almost periodic sequences, polynomial multiple recurrence and symbolic dynamics
Authors: BERGELSON V. , KUŁAGA-PRZYMUS J. , LEMAŃCZYK M. , RICHTER F. K. 
Published: January 2018

A set$R\subset \mathbb{N}$is calledrationalif it is well approximable by finite unions of arithmetic progressions, meaning that for every$\unicode[STIX]{x1D716}>0$there exists a set$B=\bigcup _{i=1}^{r}a_{i}\mathbb{N}+b_{i}$, where$a_{1},\ldots ,a_{r},b_{1},\ldots ,b_{r}\in \mathbb{N}$, such that$$\begin{eqnarray}\overline{d}(R\triangle B):=\limsup _{N\rightarrow \infty }\frac{|(R\triangle B)\cap \{1,\ldots ,N\}|}{N}<\unicode[STIX]{x1D716}.\end{eqnarray}$$Examples of rational sets include many classical sets of number-theoretical origin such as the set of squarefree numbers, the set of abundant numbers, or sets of the form$\unicode[STIX]{x1D6F7}_{x}:=\{n\in \mathbb{N}:\boldsymbol{\unicode[STIX]{x1D711}}(n)/n<x\}$, where$x\in [0,1]$and$\boldsymbol{\unicode[STIX]{x1D711}}$is Euler’s totient function. We investigate the combinatorial and dynamical properties of rational sets and obtain new results in ergodic Ramsey theory. Among other things, we show that if$R\subset \mathbb{N}$is a rational set with$\overline{d}(R)>0$, then the following are equivalent:(a)$R$is divisible, i.e. $\overline{d}(R\cap u\mathbb{N})>0$for all$u\in \mathbb{N}$;(b)$R$is an averaging set of polynomial single recurrence;(c)$R$is an averaging set of polynomial multiple recurrence.As an application, we show that if$R\subset \mathbb{N}$is rational and divisible, then for any set$E\subset \mathbb{N}$with$\overline{d}(E)>0$and any polynomials$p_{i}\in \mathbb{Q}[t]$,$i=1,\ldots ,\ell$, which satisfy$p_{i}(\mathbb{Z})\subset \mathbb{Z}$and$p_{i}(0)=0$for all$i\in \{1,\ldots ,\ell \}$, there exists$\unicode[STIX]{x1D6FD}>0$such that the set$$\begin{eqnarray}\{n\in R:\overline{d}(E\cap (E-p_{1}(n))\cap \cdots \cap (E-p_{\ell }(n)))>\unicode[STIX]{x1D6FD}\}\end{eqnarray}$$has positive lower density.Ramsey-theoretical applications naturally lead to problems in symbolic dynamics, which involverationally almost periodic sequences(sequences whose level-sets are rational). We prove that if${\mathcal{A}}$is a finite alphabet,$\unicode[STIX]{x1D702}\in {\mathcal{A}}^{\mathbb{N}}$is rationally almost periodic,$S$denotes the left-shift on${\mathcal{A}}^{\mathbb{Z}}$and$$\begin{eqnarray}X:=\{y\in {\mathcal{A}}^{\mathbb{Z}}:\text{each word appearing in}~y~\text{appears in}~\unicode[STIX]{x1D702}\},\end{eqnarray}$$then$\unicode[STIX]{x1D702}$is a generic point for an$S$-invariant probability measure$\unicode[STIX]{x1D708}$on$X$such that the measure-preserving system$(X,\unicode[STIX]{x1D708},S)$is ergodic and has rational discrete spectrum.
Particle acceleration by beating of two intense cross-focused cosh-Gaussian laser beams in plasma
Authors: Gaur Bineet , Rawat Priyanka , Purohit Gunjan 
Published: January 2018

AbstractThe effect of two intense cross-focused cosh-Gaussian laser (CGL) beams on the generation of electron plasma wave (EPW) and particle acceleration in collisionless plasma has been investigated under the relativistic–ponderomotive regime. Due to mutual interaction of two laser beams, cross-focusing takes place in plasma. The EPW is generated by the beating of two cross-focused CGL beams of frequencies ω1 and ω2. An analytical expression for the beamwidth of laser beams and EPW as well as the power of the generated EPW has been evaluated using Wentzel–Kramers–Brillouin and paraxial approximations. The energy of the accelerated electrons by the beat-wave process has also been calculated. Numerical simulations have been carried out to investigate the effect of typical laser plasma parameters on the power of excited EPW and acceleration of electrons. The results are compared with only relativistic nonlinearity and the Gaussian profile of laser beams. It is observed that CGL beams focused earlier than Gaussian beams, which significantly affected the dynamics of plasma wave excitation and particle acceleration. Numerical results indicate that there is a remarkable change in the power of generated EPW and electron acceleration in the relativistic–ponderomotive case in comparison with only relativistic case.
The spatial and metabolic basis of colony size variation
Authors: Chacón Jeremy M , Möbius Wolfram , Harcombe William R 
Published: January 2018

AbstractSpatial structure impacts microbial growth and interactions, with ecological and evolutionary consequences. It is therefore important to quantitatively understand how spatial proximity affects interactions in different environments. We tested how proximity influences colony size when either Escherichia coli or Salmonella enterica are grown on various carbon sources. The importance of colony location changed with species and carbon source. Spatially explicit, genome-scale metabolic modeling recapitulated observed colony size variation. Competitors that determine territory size, according to Voronoi diagrams, were the most important drivers of variation in colony size. However, the relative importance of different competitors changed through time. Further, the effect of location increased when colonies took up resources quickly relative to the diffusion of limiting resources. These analyses made it apparent that the importance of location was smaller than expected for experiments with S. enterica growing on glucose. The accumulation of toxic byproducts appeared to limit the growth of large colonies and reduced variation in colony size. Our work provides an experimentally and theoretically grounded understanding of how location interacts with metabolism and diffusion to influence microbial interactions.
The histone methyltransferase DOT1L inhibits osteoclastogenesis and protects against osteoporosis
Authors: Gao Yanpan , Ge Wei 
Published: January 2018

AbstractOsteoclasts are absorptive cells that play a critical role in homeostatic bone remodeling and pathological bone resorption. Emerging evidence suggests an important role of epigenetic regulation in osteoclastogenesis. In this study, we investigated the role of DOT1L, which regulates gene expression epigenetically by histone H3K79 methylation (H3K79me), during osteoclast formation. Using RANKL-induced RAW264.7 macrophage cells as an osteoclast differentiation model, we found that DOT1L and H3K79me2 levels were upregulated during osteoclast differentiation. Small molecule inhibitor- (EPZ5676 or EPZ004777) or short hairpin RNA-mediated reduction in DOT1L expression promoted osteoclast differentiation and resorption. In addition, DOT1L inhibition increased osteoclast surface area and accelerated bone-mass reduction in a mouse ovariectomy (OVX) model of osteoporosis without alter osteoblast differentiation. DOT1L inhibition increase reactive oxygen species (ROS) generation and autophagy activity, and cell migration in pre-osteoclasts. Moreover, it strengthened expression of osteoclast fusion and resorption-related protein CD9 and MMP9 in osteoclasts derived from RAW264.7. Our findings support a new mechanism of DOT1L-regulated, H3K79me2-mediated, epigenetic regulation of osteoclast differentiation, implicating DOT1L as a new therapeutic target for osteoclast dysregulation-induced disease.
Phosphorylation of ULK1 by AMPK is essential for mouse embryonic stem cell self-renewal and pluripotency
Authors: Gong Jiaqi , Gu Haifeng , Zhao Lin , Wang Liang , Liu Pinglei , Wang Fuping , Xu Haoyu , Zhao Tongbiao 
Published: January 2018

AbstractAutophagy is a catabolic process to degrade both damaged organelles and aggregated proteins in somatic cells. We have recently identified that autophagy is an executor for mitochondrial homeostasis in embryonic stem cell (ESC), and thus contribute to stemness regulation. However, the regulatory and functional mechanisms of autophagy in ESC are still largely unknown. Here we have shown that activation of ULK1 by AMPK is essential for ESC self-renewal and pluripotency. Dysfunction of Ulk1 decreases the autophagic flux in ESC, leading to compromised self-renewal and pluripotency. These defects can be rescued by reacquisition of wild-type ULK1 and ULK1(S757A) mutant, but not ULK1(S317A, S555A and S777A) and kinase dead ULK1(K46I) mutant. These data indicate that phosphorylation of ULK1 by AMPK, but not mTOR, is essential for stemness regulation in ESC. The findings highlight a critical role for AMPK-dependent phosphorylation of ULK1 pathway to maintain ESC self-renewal and pluripotency.
Insulin-like growth factor 2 is a key mitogen driving liver repopulation in mice
Authors: Wang Min-Jun , Chen Fei , Liu Qing-Gui , Liu Chang-Cheng , Yao Hao , Yu Bing , Zhang Hai-Bin , Yan He-Xin , Ye Yibiao , Chen Tao , Wangensteen Kirk J. , Wang Xin , Hu Yi-Ping , He Zhi-Ying 
Published: January 2018

AbstractHepatocyte transplantation holds great promise as an alternative to orthotopic organ transplantation in the treatment of liver diseases. However, obtaining clinically meaningful levels of liver repopulation has not been achieved because the mechanisms regulating hepatocyte proliferation in recipient livers have not yet been well characterized. In the mouse model of Hereditary Tyrosinemia Type I, the fumarylacetoacetate hydrolase-deficient (Fah−/−) mouse, we found gradually increasing expression level of insulin-like growth factor 2 (IGF2) in the hepatocytes of host livers. Similarly, high levels of IGF2 were found in the livers of patients with deficient FAH activity. Recombinant IGF2 directly promotes proliferation of primary hepatocytes in vitro. Inhibition on IGF2 expression through the interruption of PI3K/Akt and MAPK pathways significantly reduced the level of liver repopulation in Fah−/− mice. Interestingly, treatment with IGF2 before hepatocyte transplantation generally improved the amount of liver repopulation seen in various mice models of liver injury. Altogether, these findings underscore the underlying mechanisms of therapeutic liver repopulation in Fah−/− mice, and indicate that IGF2 is a potential hepatocyte mitogen for liver cell transplantation therapies.
Parallel derivation of isogenic human primed and naive induced pluripotent stem cells
Authors: Kilens Stéphanie , Meistermann Dimitri , Moreno Diego , Chariau Caroline , Gaignerie Anne , Reignier Arnaud , Lelièvre Yohann , Casanova Miguel , Vallot Céline , Nedellec Steven , Flippe Léa , Firmin Julie , Song Juan , Charpentier Eric , Lammers Jenna , Donnart Audrey , Marec Nadège , Deb Wallid , Bihouée Audrey , Le Caignec Cédric , Pecqueur Claire , Redon Richard , Barrière Paul , Bourdon Jérémie , Pasque Vincent , Soumillon Magali , Mikkelsen Tarjei S. , Rougeulle Claire , Fréour Thomas , David Laurent ,   The Milieu Intérieur Consortium, Abel Laurent , Alcover Andres , Astrom Kalla , Bousso Philippe , Bruhns Pierre , Cumano Ana , Duffy Darragh , Demangel Caroline , Deriano Ludovic , Di Santo James , Dromer Françoise , Eberl Gérard , Enninga Jost , Fellay Jacques , Freitas Antonio , Gelpi Odile , Gomperts-Boneca Ivo , Hercberg Serge , Lantz Olivier , Leclerc Claude , Mouquet Hugo , Patin Etienne , Pellegrini Sandra , Pol Stanislas , Rogge Lars , Sakuntabhai Anavaj , Schwartz Olivier , Schwikowski Benno , Shorte Spencer , Soumelis Vassili , Tangy Frédéric , Tartour Eric , Toubert Antoine , Ungeheuer Marie-Noëlle , Quintana-Murci Lluis , Albert Matthew L. 
Published: January 2018

AbstractInduced pluripotent stem cells (iPSCs) have considerably impacted human developmental biology and regenerative medicine, notably because they circumvent the use of cells of embryonic origin and offer the potential to generate patient-specific pluripotent stem cells. However, conventional reprogramming protocols produce developmentally advanced, or primed, human iPSCs (hiPSCs), restricting their use to post-implantation human development modeling. Hence, there is a need for hiPSCs resembling preimplantation naive epiblast. Here, we develop a method to generate naive hiPSCs directly from somatic cells, using OKMS overexpression and specific culture conditions, further enabling parallel generation of their isogenic primed counterparts. We benchmark naive hiPSCs against human preimplantation epiblast and reveal remarkable concordance in their transcriptome, dependency on mitochondrial respiration and X-chromosome status. Collectively, our results are essential for the understanding of pluripotency regulation throughout preimplantation development and generate new opportunities for disease modeling and regenerative medicine.
Comprehensive profiling of the ligand binding landscapes of duplexed aptamer families reveals widespread induced fit
Authors: Munzar Jeffrey D. , Ng Andy , Juncker David 
Published: January 2018

AbstractDuplexed aptamers (DAs) are ligand-responsive constructs engineered by hybridizing an aptamer with an aptamer-complementary element (ACE, e.g., a DNA oligonucleotide). Although DAs are commonly deployed, the binding dynamics of ternary ACE-aptamer–ligand systems remain underexplored, having been conventionally described by a conformational selection framework. Here we introduce aptamer-complementary element scanning (ACE-Scan) as a method to generate comprehensive hybridization, spontaneous off-rate, and induced fit ligand-binding landscapes for entire DA families. ACE-Scan reveals induced fit in DAs engineered from small molecule- and protein-binding DNA and RNA aptamers, as well as DAs engineered from the natural add riboswitch aptamer. To validate ACE-Scan, we engineer solution-phase ATP-specific DAs from 5 ACEs with varying spontaneous and induced fit off-rates, generating aptasensors with 8-fold differences in dynamic range consistent with ACE-Scan. This work demonstrates that ACE-Scan can readily map induced fit in DAs, empowering aptamers in biosensing, synthetic biology, and DNA nanomachines.
Diversity of meso-scale architecture in human and non-human connectomes
Authors: Betzel Richard F. , Medaglia John D. , Bassett Danielle S. 
Published: January 2018

AbstractBrain function is reflected in connectome community structure. The dominant view is that communities are assortative and segregated from one another, supporting specialized information processing. However, this view precludes the possibility of non-assortative communities whose complex inter-community interactions could engender a richer functional repertoire. We use weighted stochastic blockmodels to uncover the meso-scale architecture of Drosophila, mouse, rat, macaque, and human connectomes. We find that most communities are assortative, though others form core-periphery and disassortative structures, which better recapitulate observed patterns of functional connectivity and gene co-expression in human and mouse connectomes compared to standard community detection techniques. We define measures for quantifying the diversity of communities in which brain regions participate, showing that this measure is peaked in control and subcortical systems in humans, and that inter-individual differences are correlated with cognitive performance. Our report paints a more diverse portrait of connectome communities and demonstrates their cognitive relevance.
Regulation of REM and Non-REM Sleep by Periaqueductal GABAergic Neurons
Authors: Weber Franz , Hoang Do Johnny Phong , Chung Shinjae , Beier Kevin T. , Bikov Mike , Saffari Doost Mohammad , Dan Yang 
Published: January 2018

AbstractMammalian sleep consists of distinct rapid eye movement (REM) and non-REM (NREM) states. The midbrain region ventrolateral periaqueductal gray (vlPAG) is known to be important for gating REM sleep, but the underlying neuronal mechanism is not well understood. Here, we show that activating vlPAG GABAergic neurons in mice suppresses the initiation and maintenance of REM sleep while consolidating NREM sleep, partly through their projection to the dorsolateral pons. Cell-type-specific recording and calcium imaging reveal that most vlPAG GABAergic neurons are strongly suppressed at REM sleep onset and activated at its termination. In addition to the rapid changes at brain state transitions, their activity decreases gradually between REM sleep and is reset by each REM episode in a duration-dependent manner, mirroring the accumulation and dissipation of REM sleep pressure. Thus, vlPAG GABAergic neurons powerfully gate REM sleep, and their firing rate modulation may contribute to the ultradian rhythm of REM/NREM alternation.
Combined chemical genetics and data-driven bioinformatics approach identifies receptor tyrosine kinase inhibitors as host-directed antimicrobials
Authors: Korbee Cornelis J. , Heemskerk Matthias T. , Kocev Dragi , van Strijen Elisabeth , Rabiee Omid , Franken Kees L. M. C. , Wilson Louis , Savage Nigel D. L. , Džeroski Sašo , Haks Mariëlle C. , Ottenhoff Tom H. M. 
Published: January 2018

AbstractAntibiotic resistance poses rapidly increasing global problems in combatting multidrug-resistant (MDR) infectious diseases like MDR tuberculosis, prompting for novel approaches including host-directed therapies (HDT). Intracellular pathogens likeSalmonellaeandMycobacterium tuberculosis(Mtb) exploit host pathways to survive. Only very few HDT compounds targeting host pathways are currently known. In a library of pharmacologically active compounds (LOPAC)-based drug-repurposing screen, we identify multiple compounds, which target receptor tyrosine kinases (RTKs) and inhibit intracellularMtband Salmonellae more potently than currently known HDT compounds. By developing a data-driven in silico model based on confirmed targets from public databases, we successfully predict additional efficacious HDT compounds. These compounds target host RTK signaling and inhibit intracellular (MDR)Mtb. A complementary human kinome siRNA screen independently confirms the role of RTK signaling and kinases (BLK, ABL1, and NTRK1) in host control ofMtb. These approaches validate RTK signaling as a drugable host pathway for HDT against intracellular bacteria.