bluuebunny/crossref_metadata_2025 huggingface dataset:
Concordância intra e interobservador com relação ao sistema de classificação de Walch para artrose da articulação do ombro
Authors: Pajolli Lauro José Rocchetti , Carlini Marcelo Casciato , Ferrari Isabella , Matsunaga Fábio Teruo , Archetti Netto Nicola , Tamaoki Marcel Jun Sugawara
Published: May 2018

Objetivo Avaliar a concordância inter e intraobservador com relação ao sistema de classificação de Walch para artrose do ombro.

Materiais e Métodos Foram selecionadas tomografias computadorizadas da articulação do ombro de pacientes adultos entre 2012 e 2016, que foram classificadas por médicos com diferentes níveis de experiência em ortopedia. As imagens foram examinadas em três momentos distintos, e a análise foi avaliada pelo índice Kappa de Fleiss para verificar a concordância intra e interobservador.

Resultados O índice Kappa na concordância intraobservador variou entre 0,305 e 0,545. A concordância interobservador se mostrou muito baixa no fim das três avaliações (κ = 0,132).

Conclusão A concordância intraobservador com relação à classificação de Walch modificada mostrou-se variável, entre moderada e baixa. A concordância interobservador foi baixa.
Intermediate lakes of the Chulym and Kargat river valleys and their role in the evolution of the Lake Chany basin
Authors: Krivonogov S.K. , Gusev V.A. , Parkhomchuk E.V. , Zhilich S.V.
Published: May 2018

The Chulym and Kargat Rivers flow through chains of saucer-shaped depressions, which are swampy meadows or drainage lakes. In the past, all of them were lakes short-lived in different Holocene periods. These depressions accumulated a significant amount of the Chulym and Kargat runoff and thus influenced the water balance of Lake Chany. Our studies have reconstructed the history of these depressions. A model describing their filling with sediments is proposed. The lacustrine sediments penetrated by boreholes and pits are dated by the radiocarbon method at 6.3–2.0 cal. kyr BP. The data obtained explane the long existence of Lake Chany as a shallow basin and rise in its level at ~ 2 kyr BP.
Penetrating Anorectal Injury Caused by a Wild Boar Attack: A Case Report
Authors: Okano Ichiro , Midorikawa Yuki , Kushima Nobumasa , Watanabe Yui , Sugiyama Takuya , Mitachi Katsutaka , Shinohara Kazuaki , Sawada Takatoshi , Inagaki Katsunori
Published: May 2018

Wild boar attacks have rarely been reported in the medical literature. This is the case of an 83-year-old male farmer who was assaulted from behind by an injured adult wild boar. He presented with hemorrhagic shock after sustaining injuries to the right profunda femoris artery and right sciatic nerve as well as significant soft-tissue injuries, bilateral iliac wing fractures, an open pneumothorax, and an anorectal injury. The anorectal injury was treated with fecal diversion but was complicated by soft-tissue infection in the surrounding dead space. The patient needed multiple operations, including removal of the distal rectum and creation of a permanent colostomy. In this report, we highlighted the characteristics of anorectal trauma caused by a wild boar attack. We conclude that penetrating anorectal injuries caused by this type of attack can be associated with extensive soft-tissue damage despite externally appearing to be simple puncture wounds. Anorectal combat injuries have demonstrated similar extensive surrounding soft-tissue injuries and propensity for infection; therefore, this case supports adopting a similar treatment strategy, that of serial and radical debridement, to treat certain wild boar injuries.
MISSING THE POOREST IN RURAL AREAS? TARGETING LOW INCOME VOTERS IN MAYORAL ELECTIONS
Authors: Amick Joe
Published: May 2018

This article utilizes an original household survey of two regency-level elections in Indonesia to explore campaign targeting. It uses a list experiment to show that direct survey questions about accepting transfers from campaigns elicit honest responses from respondents in Indonesia. Although the relationship between income and whether a respondent accepted transfers from political campaigns decreases over the entire distribution of income, it increases initially, producing a curvilinear relationship between income and accepting transfers from campaigns. This article argues that the poorest voters face barriers to being targeted by campaigns. However, these barriers recede as they become relatively richer, at which point a negative relationship is found due to diminishing marginal utility of accepting these transfers. Finally, in-kind transfers, as opposed to cash transfers, target low-income voters more effectively.
Rayleigh–Bénard convection in a creeping solid with melting and freezing at either or both its horizontal boundaries
Authors: Labrosse Stéphane , Morison Adrien , Deguen Renaud , Alboussière Thierry
Published: May 2018

Solid-state convection can take place in the rocky or icy mantles of planetary objects, and these mantles can be surrounded above or below or both by molten layers of similar composition. A flow towards the interface can proceed through it by changing phase. This behaviour is modelled by a boundary condition taking into account the competition between viscous stress in the solid, which builds topography of the interface with a time scale $\unicode[STIX]{x1D70F}_{\unicode[STIX]{x1D702}}$, and convective transfer of the latent heat in the liquid from places of the boundary where freezing occurs to places of melting, which acts to erase topography, with a time scale $\unicode[STIX]{x1D70F}_{\unicode[STIX]{x1D719}}$. The ratio $\unicode[STIX]{x1D6F7}=\unicode[STIX]{x1D70F}_{\unicode[STIX]{x1D719}}/\unicode[STIX]{x1D70F}_{\unicode[STIX]{x1D702}}$ controls whether the boundary condition is the classical non-penetrative one ($\unicode[STIX]{x1D6F7}\rightarrow \infty$) or allows for a finite flow through the boundary (small $\unicode[STIX]{x1D6F7}$). We study Rayleigh–Bénard convection in a plane layer subject to this boundary condition at either or both its boundaries using linear and weakly nonlinear analyses. When both boundaries are phase-change interfaces with equal values of $\unicode[STIX]{x1D6F7}$, a non-deforming translation mode is possible with a critical Rayleigh number equal to $24\unicode[STIX]{x1D6F7}$. At small values of $\unicode[STIX]{x1D6F7}$, this mode competes with a weakly deforming mode having a slightly lower critical Rayleigh number and a very long wavelength, $\unicode[STIX]{x1D706}_{c}\sim 8\sqrt{2}\unicode[STIX]{x03C0}/3\sqrt{\unicode[STIX]{x1D6F7}}$. Both modes lead to very efficient heat transfer, as expressed by the relationship between the Nusselt and Rayleigh numbers. When only one boundary is subject to a phase-change condition, the critical Rayleigh number is $\mathit{Ra}_{c}=153$ and the critical wavelength is $\unicode[STIX]{x1D706}_{c}=5$. The Nusselt number increases approximately two times faster with the Rayleigh number than in the classical case with non-penetrative conditions, and the average temperature diverges from $1/2$ when the Rayleigh number is increased, towards larger values when the bottom boundary is a phase-change interface.
Interaction of a pair of ferrofluid drops in a rotating magnetic field
Authors: Qiu Mingfeng , Afkhami Shahriar , Chen Ching-Yao , Feng James J.
Published: May 2018

We use two-dimensional numerical simulation to study the interaction between a pair of ferrofluid drops suspended in a rotating uniform magnetic field. Numerical results show four distinct regimes over the range of parameters tested: independent spin, planetary motion, drop locking and direct coalescence. These are in qualitative agreement with experiments, and the transition between them can be understood from the competition between magnetophoretic forces and viscous drag. We further analyse in detail the planetary motion, i.e. the revolution of the drops around each other while each spins in phase with the external magnetic field. For drops, as opposed to solid microspheres, the interaction is dominated by viscous sweeping, a form of hydrodynamic interaction. Magnetic dipole–dipole interaction via mutual induction only plays a secondary role. This insight helps us explain novel features of the planetary revolution of the ferrofluid drops that cannot be explained by a dipole model, including the increase of the angular velocity of planetary motion with the rotational rate of the external field, and the attainment of a limit separation between the drops that is independent of the initial separation.
On turbulent friction in straight ducts with complex cross-section: the wall law and the hydraulic diameter
Authors: Pirozzoli Sergio
Published: May 2018

We develop predictive formulae for frictional resistance in ducts with complex cross-sectional shape based on the use of the log law and neglect of wall shear stress non-uniformities. The traditional hydraulic diameter naturally emerges from the analysis as the controlling length scale for common duct shapes such as triangles and regular polygons. The analysis also suggests that a new effective diameter should be used in more general cases, yielding corrections of a few percent to friction estimates based on the traditional hydraulic diameter. Fair, but consistent, predictive improvement is shown for duct geometries of practical relevance, including rectangular and annular ducts, and circular rod bundles.
Phase-response analysis of synchronization for periodic flows
Authors: Taira Kunihiko , Nakao Hiroya
Published: May 2018

We apply phase-reduction analysis to examine synchronization properties of periodic fluid flows. The dynamics of unsteady flows is described in terms of the phase dynamics, reducing the high-dimensional fluid flow to its single scalar phase variable. We characterize the phase response to impulse perturbations, which can in turn quantify the influence of periodic perturbations on the unsteady flow. These insights from phase-based analysis uncover the condition for synchronization. In the present work, we study as an example the influence of periodic external forcing on an unsteady cylinder wake. The condition for synchronization is identified and agrees closely with results from direct numerical simulations. Moreover, the analysis reveals the optimal forcing direction for synchronization. Phase-response analysis holds potential to uncover lock-on characteristics for a range of periodic flows.
ON OVERTWISTED CONTACT SURGERIES
Authors: ONARAN SINEM
Published: May 2018

In this paper, we obtain a new result for overtwisted contact $(+1/n)$-surgery. We also give a counterexample to a conjecture by James Conway on overtwistedness of manifolds obtained by contact surgery.
Prenatal malnutrition and adult cognitive impairment: a natural experiment from the 1959–1961 Chinese famine
Authors: He Ping , Liu Li , Salas J. M. Ian , Guo Chao , Cheng Yunfei , Chen Gong , Zheng Xiaoying
Published: May 2018

The current measures of cognitive functioning in adulthood do not indicate a long-term association with prenatal exposure to the Dutch famine. However, whether such association emerges in China is poorly understood. We aimed to investigate the potential effect of prenatal exposure to the 1959–1961 Chinese famine on adult cognitive impairment. We obtained data from the Second National Sample Survey on Disability implemented in thirty-one provinces in 2006, and restricted our analysis to 387 093 individuals born in 1956–1965. Cognitive impairment was defined as intelligence quotient (IQ) score under 70 and IQ of adults was evaluated by the Wechsler Adult Intelligence Scale – China Revision. Famine severity was defined as excess death rate. The famine impact on adult cognitive impairment was estimated by difference-in-difference models, established by examining the variations of famine exposure across birth cohorts. Results show that compared with adults born in 1956–1958, those who were exposed to Chinese famine during gestation (born in 1959–1961) were at greater risk of cognitive impairment in the total sample. Stratified analyses showed that this effect was evident in males and females, but only in rural, not in urban areas. In conclusion, prenatal exposure to famine had an enduring deleterious effect on risk of cognitive impairment in rural adults.
Recruitment advertising for Antarctic personnel: between adventure and routine
Authors: Nielsen Hanne E. F. , Jaksic Cyril
Published: May 2018

This paper examines how Antarctica has been depicted in recruitment material, and compares the expectations set up in the advertising imagery with the reality of expeditioners’ experiences. Textual analyses of advertisements and job descriptions are used to reveal dominant themes, including the trope of extremity, while interviews with those who have spent time on the ice provide reflections on the actual challenges encountered when working in Antarctica, such as boredom. Much of the popular discourse around Antarctica continues to centre on the Heroic Era (1895–1922), a time of exploration typified by men pitting themselves against nature and striding out into unchartered expanses of ice. Although modern day life on Antarctic stations differs markedly from the extreme conditions experienced by early explorers, the continent continues to be associated with notions of toughness and extremity. We argue that in some cases, advertisements may actually target the wrong audience. This has important implications for how an Antarctic station as a workplace is conceptualised, and then experienced by those who head south, with potential detrimental effects.
Revisiting Labor Activism in Iran: Some Notes on the Vatan Factory Strike in 1931
Authors: Afacan Serhan
Published: May 2018

This article discusses the discursive practices of Iranian workers between 1921 and 1941, with a particular focus on the Vatan Factory strike, which took place in Isfahan in May 1931. Initially, the article provides a brief background on the industrialization process of the era for a better contextualization of the factory and the strike under study. Then, it discusses Iranian workers’ self-perceptions and the discursive practices and strategies they used in their engagement with the ruling classes, by utilizing the petitions they sent to various authorities. And finally, it elaborates on the Vatan Factory strike in order to gain a better understanding of workers’ self-representations and the changing dynamics between them and the official authorities. In the main, this article suggests that notwithstanding the confrontational nature of this particular labor action, striking workers’ discursive engagement was in conformity with the developing labor discourse at large.
The New Speech Politics
Authors: Raine Barnaby
Published: May 2018

In engaging the popularity of “free speech” as a conservative battle cry in recent years, this article poses two questions: What particular conception of that demand does the right defend, and how should the left respond? Finding that conservatives have moved from a “negative” to a “positive” understanding of this freedom selectively applied, this article presents the consistent application of that positive understanding of free speech as a challenge to concentrations of power that conspire to privilege some speech over others. Turning to recent attempts by graduate students on North American campuses to unionize, the article attempts to ground a reading of union rights as free speech rights. Free speech is presented as a useful frame through which to think about political struggles more generally, though the article cautions against treating free speech as an invariably desirable principle.
Populism is Not in the Air (but maybe it should be)
Authors: Semán Ernesto
Published: May 2018

Analogies between the rise of Donald Trump in the United States and populist leaders in Latin America are an emblematic case of misleading comparative analysis. They hide the ideological core of Trumpism, which undermines collective action and its emblematic institution, organized labor, dismantling the protections it attained during the twentieth century. In particular, references to Argentina's Juan Perón obscure Trump's emphasis on individual economic freedom, property rights, and the naturalization of inequality, values engrained in American political thinking. They also distort the populist legacies in Latin America. Populist leaders in the postwar years challenged liberal democratic thinking by posing that social rights and collective prerogatives for excluded groups should prevail over individual citizenship in order to expand political democracy. That legacy is not only alien to Trumpism; it might also be the main weapon to fight against it.
Evaluation of Cotton Responses to Fomesafen-Based Treatments Applied Preemergence
Authors: Li Xiao , Grey Timothy , Vencill William , Freeman James , Price Katilyn , Cutts George , Price Andrew
Published: May 2018

Fomesafen provides effective control of glyphosate-resistant Palmer amaranth in cotton. However, cotton seedlings can be injured when fomesafen is applied PRE. Therefore, greenhouse and field experiments were conducted at Athens, GA, and at six locations in Alabama and Georgia in 2013 and 2016 to evaluate cotton growth and yield response to fomesafen applied PRE at 70, 140, 280, 560, 1,120, or 2,240 g ai ha−1, and in combination with pendimethalin, diuron, acetochlor, and fluridone at 1×label rates. Greenhouse bioassays indicated that fomesafen reduced cotton height and dry weight with increasing rate in Cecil sandy loam and Tifton loamy sand but not in Greenville sandy clay loam––possibly as a result of this soil’s higher organic matter (OM) and clay content. Fomesafen applied at 2,240 g ai ha−1reduced cotton stand by as much as 83% compared to the nontreated check (NTC) at all field locations except Alabama’s Macon and Baldwin counties, and 1,120 g ai ha−1reduced cotton stand only at Pulaski County, GA, by 52%. Cotton height was reduced by the two highest rates of fomesafen at all locations except Clarke County, GA, and Baldwin County, AL. Injury data indicated more visual injury followed increasing fomesafen rates, and high-rate treatments produced more injury in sandier soils. Cotton yield was unaffected by herbicide treatments at any location, except for the 1,120 g ai ha−1rate at Pulaski County (49% yield loss compared to NTC), 2,240 g ai ha−1at Pulaski County (72% yield loss), and Tift County (29% yield loss). These data indicated cotton yield should not be negatively affected by fomesafen applied PRE alone within label rates or in combination with pendimethalin, diuron, acetochlor, and fluridone at 1×label rates, although some visual injury, or stand or height reduction may occur early in the growing season.
It’s So UnFAIR!
Authors: Desai Ankur
Published: May 2018

A recent paper in JGR: Biogeosciences demonstrates that sharing data has positive benefits not just for the scientific community but also for the one doing the sharing.
Transcriptome analysis in whole blood reveals increased microbial diversity in schizophrenia
Authors: Olde Loohuis Loes M. , Mangul Serghei , Ori Anil P. S. , Jospin Guillaume , Koslicki David , Yang Harry Taegyun , Wu Timothy , Boks Marco P. , Lomen-Hoerth Catherine , Wiedau-Pazos Martina , Cantor Rita M. , de Vos Willem M. , Kahn René S. , Eskin Eleazar , Ophoff Roel A.
Published: May 2018

The role of the human microbiome in health and disease is increasingly appreciated. We studied the composition of microbial communities present in blood across 192 individuals, including healthy controls and patients with three disorders affecting the brain: schizophrenia, amyotrophic lateral sclerosis, and bipolar disorder. By using high-quality unmapped RNA sequencing reads as candidate microbial reads, we performed profiling of microbial transcripts detected in whole blood. We were able to detect a wide range of bacterial and archaeal phyla in blood. Interestingly, we observed an increased microbial diversity in schizophrenia patients compared to the three other groups. We replicated this finding in an independent schizophrenia case–control cohort. This increased diversity is inversely correlated with estimated cell abundance of a subpopulation of CD8+ memory T cells in healthy controls, supporting a link between microbial products found in blood, immunity and schizophrenia.
Iron overload promotes mitochondrial fragmentation in mesenchymal stromal cells from myelodysplastic syndrome patients through activation of the AMPK/MFF/Drp1 pathway
Authors: Zheng Qingqing , Zhao Youshan , Guo Juan , Zhao Sida , Fei Chengming , Xiao Chao , Wu Dong , Wu Lingyun , Li Xiao , Chang Chunkang
Published: May 2018

Iron overload (IO) has been reported to contribute to mesenchymal stromal cell (MSC) damage, but the precise mechanism has yet to be clearly elucidated. In this study, we found that IO increased cell apoptosis and lowered cell viability in MSCs, accompanied by extensive mitochondrial fragmentation and autophagy enhancement. All these effects were reactive oxygen species (ROS) dependent. In MSCs with IO, the ATP concentrations were significantly reduced due to high ROS levels and low electron respiratory chain complex (ETC) II/III activity. Reduced ATP phosphorylated AMP-activated protein kinase (AMPK). Activation of AMPK kinase complexes triggered mitochondrial fission. Moreover, gene knockout of AMPK via CRISPR/Cas9 reduced cell apoptosis, enhanced cell viability and attenuated mitochondrial fragmentation and autophagy caused by IO in MSCs. Further, AMPK-induced mitochondrial fragmentation of MSCs with IO was mediated via phosphorylation of mitochondrial fission factor (MFF), a mitochondrial outer-membrane receptor for the GTPase dynamin-related protein 1 (Drp1). Gene knockdown of MFF reversed AMPK-induced mitochondrial fragmentation in MSCs with IO. In addition, MSCs from IO patients with myelodysplastic syndrome (MDS) showed increased cell apoptosis, decreased cell viability, higher ROS levels, lower ATP concentrations and increased mitochondrial fragmentation compared with MSCs from non-IO patients. In addition, iron chelation or antioxidant weakened the activity of the AMPK/MFF/Drp1 pathway in MDS-MSCs with IO from several patients, accompanied by attenuation of mitochondrial fragmentation and autophagy. Taken together, the AMPK/MFF/Drp1 pathway has an important role in the damage to MDS-MSCs caused by IO.
HOXB9 promotes endometrial cancer progression by targeting E2F3
Authors: Wan Junhu , Liu Hongyang , Feng Quanling , Liu Jun , Ming Liang
Published: May 2018

HOXB9, as a HOX family transcription factor, playing a significant role in embryonic development and cancer progression. However, the function of HOXB9 and its precise mechanism in regulating endometrial cancer progression remains unknown. Here, we demonstrated that the expression of HOXB9 was increased in endometrial cancer, and associated with histological grade and lymph node metastasis. In addition, elevated HOXB9 predicts a poor prognosis in endometrial cancer patients. Interestingly, bioinformatics analysis of TCGA cancer database showed that HOXB9 expression is positively correlated with E2F3 expression. Moreover, HOXB9 promoted E2F3 expression by directly targeting to its promoter. Furthermore, we found that knocking down E2F3 abolished the ability of HOXB9 in enhancing cell migration. Taken together, for the first, we demonstrated the function and mechanism of HOXB9 in regulating endometrial cancer progression, and indicated HOXB9 may be a novel prognostic marker of endometrial cancer.
Nucleolar TRF2 attenuated nucleolus stress-induced HCC cell-cycle arrest by altering rRNA synthesis
Authors: Yuan Fuwen , Xu Chenzhong , Li Guodong , Tong Tanjun
Published: May 2018

The nucleolus is an important organelle that is responsible for the biogenesis of ribosome RNA (rRNA) and ribosomal subunits assembly. It is also deemed to be the center of metabolic control, considering the critical role of ribosomes in protein translation. Perturbations of rRNA synthesis are closely related to cell proliferation and tumor progression. Telomeric repeat-binding factor 2 (TRF2) is a member of shelterin complex that is responsible for telomere DNA protection. Interestingly, it was recently reported to localize in the nucleolus of human cells in a cell-cycle-dependent manner, while the underlying mechanism and its role on the nucleolus remained unclear. In this study, we found that nucleolar and coiled-body phosphoprotein 1 (NOLC1), a nucleolar protein that is responsible for the nucleolus construction and rRNA synthesis, interacted with TRF2 and mediated the shuttle of TRF2 between the nucleolus and nucleus. Abating the expression of NOLC1 decreased the nucleolar-resident TRF2. Besides, the nucleolar TRF2 could bind rDNA and promoted rRNA transcription. Furthermore, in hepatocellular carcinoma (HCC) cell lines HepG2 and SMMC7721, TRF2 overexpression participated in the nucleolus stress-induced rRNA inhibition and cell-cycle arrest.
Small GTPases and BAR domain proteins regulate branched actin polymerisation for clathrin and dynamin-independent endocytosis
Authors: Sathe Mugdha , Muthukrishnan Gayatri , Rae James , Disanza Andrea , Thattai Mukund , Scita Giorgio , Parton Robert G. , Mayor Satyajit
Published: May 2018

Using real-time TIRF microscopy imaging, we identify sites of clathrin and dynamin-independent CLIC/GEEC (CG) endocytic vesicle formation. This allows spatio-temporal localisation of known molecules affecting CG endocytosis; GBF1 (a GEF for ARF1), ARF1 and CDC42 which appear sequentially over 60 s, preceding scission. In an RNAi screen for BAR domain proteins affecting CG endocytosis, IRSp53 and PICK1, known interactors of CDC42 and ARF1, respectively, were selected. Removal of IRSp53, a negative curvature sensing protein, abolishes CG endocytosis. Furthermore, the identification of ARP2/3 complex at CG endocytic sites, maintained in an inactive state reveals a function for PICK1, an ARP2/3 inhibitor. The spatio-temporal sequence of the arrival and disappearance of the molecules suggest a mechanism for a clathrin and dynamin-independent endocytic process. Coincident with the loss of PICK1 by GBF1-activated ARF1, CDC42 recruitment leads to the activation of IRSp53 and the ARP2/3 complex, resulting in a burst of F-actin polymerisation potentially powering scission.
Biosynthetic pathway for furanosteroid demethoxyviridin and identification of an unusual pregnane side-chain cleavage
Authors: Wang Gao-Qian , Chen Guo-Dong , Qin Sheng-Ying , Hu Dan , Awakawa Takayoshi , Li Shao-Yang , Lv Jian-Ming , Wang Chuan-Xi , Yao Xin-Sheng , Abe Ikuro , Gao Hao
Published: May 2018

Furanosteroids, represented by wortmannin, viridin, and demethoxyviridin, are a special group of fungal-derived, highly oxygenated steroids featured by an extra furan ring. They are well-known nanomolar-potency inhibitors of phosphatidylinositol 3-kinase and widely used in biological studies. Despite their importance, the biosyntheses of these molecules are poorly understood. Here, we report the identification of the biosynthetic gene cluster for demethoxyviridin, consisting of 19 genes, and among them 15 biosynthetic genes, including six cytochrome P450 monooxygenase genes, are deleted. As a result, 14 biosynthetic intermediates are isolated, and the biosynthetic pathway for demethoxyviridin is elucidated. Notably, the pregnane side-chain cleavage requires three enzymes: flavin-dependent Baeyer-Villiger monooxygenase, esterase, and dehydrogenase, in sharp contrast to the single cytochrome P450-mediated process in mammalian cells. Structure–activity analyses of these obtained biosynthetic intermediates reveal that the 3-keto group, the C1β–OH, and the aromatic ring C are important for the inhibition of phosphatidylinositol 3-kinase.
qSR: a quantitative super-resolution analysis tool reveals the cell-cycle dependent organization of RNA Polymerase I in live human cells
Authors: Andrews J. O. , Conway W. , Cho W -K. , Narayanan A. , Spille J -H. , Jayanth N. , Inoue T. , Mullen S. , Thaler J. , Cissé I. I.
Published: May 2018

We present qSR, an analytical tool for the quantitative analysis of single molecule based super-resolution data. The software is created as an open-source platform integrating multiple algorithms for rigorous spatial and temporal characterizations of protein clusters in super-resolution data of living cells. First, we illustrate qSR using a sample live cell data of RNA Polymerase II (Pol II) as an example of highly dynamic sub-diffractive clusters. Then we utilize qSR to investigate the organization and dynamics of endogenous RNA Polymerase I (Pol I) in live human cells, throughout the cell cycle. Our analysis reveals a previously uncharacterized transient clustering of Pol I. Both stable and transient populations of Pol I clusters co-exist in individual living cells, and their relative fraction vary during cell cycle, in a manner correlating with global gene expression. Thus, qSR serves to facilitate the study of protein organization and dynamics with very high spatial and temporal resolutions directly in live cell.
Heritability of Sleep EEG Topography in Adolescence: Results from a Longitudinal Twin Study
Authors: Markovic Andjela , Achermann Peter , Rusterholz Thomas , Tarokh Leila
Published: May 2018

The topographic distribution of sleep EEG power is a reflection of brain structure and function. The goal of this study was to examine the degree to which genes contribute to sleep EEG topography during adolescence, a period of brain restructuring and maturation. We recorded high-density sleep EEG in monozygotic (MZ; n = 28) and dizygotic (DZ; n = 22) adolescent twins (mean age = 13.2 ± 1.1 years) at two time points 6 months apart. The topographic distribution of normalized sleep EEG power was examined for the frequency bands delta (1–4.6 Hz) to gamma 2 (34.2–44 Hz) during NREM and REM sleep. We found highest heritability values in the beta band for NREM and REM sleep (0.44 ≤ h2 ≤ 0.57), while environmental factors shared amongst twin siblings accounted for the variance in the delta to sigma bands (0.59 ≤ c2 ≤ 0.83). Given that both genetic and environmental factors are reflected in sleep EEG topography, our results suggest that topography may provide a rich metric by which to understand brain function. Furthermore, the frequency specific parsing of the influence of genetic from environmental factors on topography suggests functionally distinct networks and reveals the mechanisms that shape these networks.
Novel Polymer-Free Everolimus-Eluting Stent Fabricated using Femtosecond Laser Improves Re-endothelialization and Anti-inflammation
Authors: Bae In-Ho , Jeong Myung Ho , Lim Kyung Seob , Park Dae Sung , Shim Jae Won , Park Jun-Kyu , Oh Kwang Hwan , Jin Mi Rim , Sim Doo Sun
Published: May 2018

The aim of this study was to fabricate a novel polymer-free everolimus-eluting stent with nanostructure using a femtosecond laser (FSL). The stent were coated with everolimus (EVL) using FSL and electrospinning processes. The surface was rendered hydrophobic, which negatively affected both platelet adhesion (82.1%) and smooth muscle cell response. Animal study was performed using a porcine coronary restenosis model. The study groups were divided into 1) bare metal stent (BMS), 2) poly(L-lactide) (PLA)-based EVL drug eluting stent (DES), 3) commercial EVL-eluting DES, and 4) FSL-EVL-DES. After four weeks of stent implantation, various analyses were performed. Quantitative analysis showed that the amount of in-stent restenosis was higher in the BMS group (BMS; 27.8 ± 2.68%, PLA-based DES; 12.2 ± 0.57%, commercial DES; 9.8 ± 0.28%, and FSL-DES; 9.3 ± 0.25%,n = 10,p < 0.05). Specifically, the inflammation score was reduced in the FSL-DES group (1.9 ± 0.39,n = 10,p < 0.05). The increment in re-endothelialization in the FSL-DES group was confirmed by immunofluorescence analysis. Taken together, the novel polymer-free EVL-eluting stent fabricated using FSL can be an innovative DES with reduced risk of ISR, thrombosis, and inflammation.
Trivalent soluble TNF Receptor, a potent TNF-α antagonist for the treatment collagen-induced arthritis
Authors: Cui Xiaofang , Chang Linmo , Li Youwei , Lv Qianrui , Wang Fei , Lin Yaxian , Li Weiyang , Meade Jonathan D. , Walden Jamie C. , Liang Peng
Published: May 2018

Tumor necrosis factor is a major pro-inflammatory cytokine which triggers various physiological consequences by binding to and trimerizing its receptors, and has been the single most sought-after drug target for intervening autoimmune diseases such as rheumatoid arthritis and psoriasis. However, current TNF-α blockers, including soluble receptor-Fc fusion and therapeutic antibodies, are all dimeric in structure, whereas their target TNF-α itself is homotrimeric in nature. Here we describe the development of a trivalent soluble TNF receptor and show that it is a more potent than the dimeric TNF receptor decoys in inhibiting TNF-α signaling bothin vitroandin vivo. The process involves gene fusion between a soluble receptor TNFRII with a ligand binding domain and a trimerization tag from the C-propeptide of human collagen (Trimer-Tag), which is capable of self-assembly into a covalently linked trimer. We show that the homotrimeric soluble TNF receptor (TNFRII-Trimer) produced with such method is more potent in ligand binding kinetics and cell based bioassays, as well as more efficacious in attenuating collagen-induced arthritis (CIA) in a mouse model than its dimeric TNFRII-Fc counterpart. Thus, this work demonstrates the proof of concept of Trimer-Tag and provides a new platform for rational designs of next generation biologic drugs.
A machine learning model with human cognitive biases capable of learning from small and biased datasets
Authors: Taniguchi Hidetaka , Sato Hiroshi , Shirakawa Tomohiro
Published: May 2018

Human learners can generalize a new concept from a small number of samples. In contrast, conventional machine learning methods require large amounts of data to address the same types of problems. Humans have cognitive biases that promote fast learning. Here, we developed a method to reduce the gap between human beings and machines in this type of inference by utilizing cognitive biases. We implemented a human cognitive model into machine learning algorithms and compared their performance with the currently most popular methods, naïve Bayes, support vector machine, neural networks, logistic regression and random forests. We focused on the task of spam classification, which has been studied for a long time in the field of machine learning and often requires a large amount of data to obtain high accuracy. Our models achieved superior performance with small and biased samples in comparison with other representative machine learning methods.
A novel potential primary method for quantification of enantiomers by high performance liquid chromatography-circular dichroism
Authors: Luo Yi , Wu Liqing , Yang Bin , Jin Youxun , Zheng Kangle , He Zhangjing
Published: May 2018

Primary methods play an important role in metrology. They can be used for the value assignment of certified reference materials, enabling the accuracy and comparability of the measurement. A novel potential primary method for enantiomer quantitation based on high-performance liquid chromatography-circular dichroism is described using L-phenylalanine as an example. The optimal quantitation range of L-Phe was from 0.1 mg/g to 1.2 mg/g, where both the relative bias and method variance were lower than 1%. The LOD and LOQ were 4 μg/g and 30 μg/g, respectively. The proposed method was also applied to the determination of the mass fraction of pure porcine insulin in solid. The average mass fraction obtained was 0.922 g/g with a RSD of 1.5%, and the associated relative uncertainty is 3.8% (k = 2), which agreed well with that obtained from the traditional isotope dilution mass spectrometry method. The LOD and LOQ for insulin quantitation were found to be 0.12 mg/g and 0.44 mg/g, respectively. The proposed method can be entirely described and understood by equations and a complete uncertainty statement can be defined in SI units.Therefore, it may be a potential primary method useful for the quantification of chiral compounds and proteins, and a supplementary method to the traditional isotope dilution mass spectrometry approach.
Auto-FPFA: An Automated Microscope for Characterizing Genetically Encoded Biosensors
Authors: Nguyen Tuan A. , Puhl Henry L. , Pham An K. , Vogel Steven S.
Published: May 2018

Genetically encoded biosensors function by linking structural change in a protein construct, typically tagged with one or more fluorescent proteins, to changes in a biological parameter of interest (such as calcium concentration, pH, phosphorylation-state, etc.). Typically, the structural change triggered by alterations in the bio-parameter is monitored as a change in either fluorescent intensity, or lifetime. Potentially, other photo-physical properties of fluorophores, such as fluorescence anisotropy, molecular brightness, concentration, and lateral and/or rotational diffusion could also be used. Furthermore, while it is likely that multiple photo-physical attributes of a biosensor might be altered as a function of the bio-parameter, standard measurements monitor only a single photo-physical trait. This limits how biosensors are designed, as well as the accuracy and interpretation of biosensor measurements. Here we describe the design and construction of an automated multimodal-microscope. This system can autonomously analyze 96 samples in a micro-titer dish and for each sample simultaneously measure intensity (photon count), fluorescence lifetime, time-resolved anisotropy, molecular brightness, lateral diffusion time, and concentration. We characterize the accuracy and precision of this instrument, and then demonstrate its utility by characterizing three types of genetically encoded calcium sensors as well as a negative control.
Dissection of niche competition between introduced and indigenous arbuscular mycorrhizal fungi with respect to soybean yield responses
Authors: Niwa Rieko , Koyama Takuya , Sato Takumi , Adachi Katsuki , Tawaraya Keitaro , Sato Shusei , Hirakawa Hideki , Yoshida Shigenobu , Ezawa Tatsuhiro
Published: May 2018

Arbuscular mycorrhizal (AM) fungi associate with most land plants and deliver phosphorus to the host. Identification of biotic/abiotic factors that determine crop responses to AM fungal inoculation is an essential step for successful application of the fungi in sustainable agriculture. We conducted three field trials on soybean with a commercial inoculum and developed a new molecular tool to dissect interactions between the inoculum and indigenous fungi on the MiSeq sequencing platform. Regression analysis indicated that sequence read abundance of the inoculum fungus was the most significant factor that determined soybean yield responses to the inoculation, suggesting that dominance of the inoculum fungus is a necessary condition for positive yield responses. Agricultural practices (fallow/cropping in the previous year) greatly affected the colonization levels (i.e. read abundances) of the inoculum fungus via altering the propagule density of indigenous AM fungi. Analysis of niche competition revealed that the inoculum fungus competed mainly with the indigenous fungi that are commonly distributed in the trial sites, probably because their life-history strategy is the same as that of the inoculum fungus. In conclusion, we provide a new framework for evaluating the significance of environmental factors towards successful application of AM fungi in agriculture.
Design, characterization and in vivo performance of synthetic 2 mm-diameter vessel grafts made of PVA-gelatin blends
Authors: Atlan M. , Simon-Yarza T. , Ino J. M. , Hunsinger V. , Corté L. , Ou P. , Aid-Launais R. , Chaouat M. , Letourneur D.
Published: May 2018

Since the development of the first vascular grafts, fabrication of vessel replacements with diameters smaller than 6 mm remains a challenge. The present work aimed to develop PVA (poly (vinyl alcohol))-gelatin hybrids as tubes suitable for replacement of very small vessels and to evaluate their performance using a rat abdominal aorta interposition model. PVA-gelatin hybrid tubes with internal and external diameters of 1.4 mm and 1.8 mm, respectively, composed of 4 different gelatin ratios were prepared using a one-step strategy with both chemical and physical crosslinking. By 3D Time of Flight MRI, Doppler-Ultrasound, Computed Tomography angiography and histology, we demonstrated good patency rates with the 1% gelatin composition until the end of the study at 3 months (50% compared to 0% of PVA control grafts). A reduction of the patency rate during the time of implantation suggested some loss of properties of the hybrid material in vivo, further confirmed by mechanical evaluation until one year. In particular, stiffening and reduction of compliance of the PVA-gelatin grafts was demonstrated, which might explain the observed long-term changes in patency rate. These encouraging results confirm the potential of PVA-gelatin hybrids as ready-to-use vascular grafts for very small vessel replacement.
Association of BET1L and TNRC6B with uterine leiomyoma risk and its relevant clinical features in Han Chinese population
Authors: Liu Bailing , Wang Tao , Jiang Jue , Li Miao , Ma Wenqi , Wu Haibin , Zhou Qi
Published: May 2018

Previous studies have shown that uterine leiomyomas (UL) are benign tumours with contributions from environmental and genetic factors. We aimed to replicate two initial significant genetic factors, TNRC6B and BET1L, in a Han Chinese population. A total of 2,055 study subjects were recruited, and 55 SNPs mapped to TNRC6B and BET1L were selected and genotyped in samples from these subjects. Genetic associations were analysed at both the single marker and haplotype levels. Associations between targeted SNPs and relevant clinical features of UL were analysed in case only samples. Functional consequences of significant SNPs were analysed by bioinformatics tools. Two SNPs, rs2280543 from BET1L (χ2 = 18.3, OR = 0.64, P = 1.87 × 10−5) and rs12484776 from TNRC6B (χ2 = 19.7, OR = 1.40, P = 8.91 × 10−6), were identified as significantly associated with the disease status of UL. Rs2280543 was significantly associated with the number of fibroid nodes (P = 0.0007), while rs12484776 was significantly associated with node size (χ2 = 54.88, P = 3.44 × 10−11). Both SNPs were a significant eQTL for their genes. In this study, we have shown that both BET1L and TNRC6B contributed to the risk of UL in Chinese women. Significant SNPs from BET1L and TNRC6B were also identified as significantly associated with the number of fibroid nodes and the size of the node, respectively.
Caller characteristics influence recruitment to collective anti-predator events in jackdaws
Authors: Woods Richard D. , Kings Michael , McIvor Guillam E. , Thornton Alex
Published: May 2018

Across the animal kingdom, examples abound of individuals coming together to repel external threats. When such collective actions are initiated by recruitment signals, individuals may benefit from being selective in whom they join, so the identity of the initiator may determine the magnitude of the group response. However, the role of signaller discrimination in coordinating group-level responses has yet to be tested. Here we show that in wild jackdaws, a colonial corvid species, collective responses to anti-predator recruitment calls are mediated by caller characteristics. In playbacks next to nestboxes, the calls of nestbox residents attracted most recruits, followed in turn by other colony members, non-colony members and rooks (a sympatric corvid). Playbacks in fields outside nestbox colonies, where the immediate threat to broods was lower, showed similar results, with highest recruitment to nearby colony members’ calls. Responses were further influenced by caller sex: calls from non-colony member females were less likely to elicit responsive scolding by recruits than other calls, potentially reflecting social rank associated with sex and colony membership. These results show that vocal discrimination mediates jackdaws’ collective responses and highlight the need for further research into the cognitive basis of collective actions in animal groups.
Evaluation of pre-analytical factors affecting plasma DNA analysis
Authors: Markus Havell , Contente-Cuomo Tania , Farooq Maria , Liang Winnie S. , Borad Mitesh J. , Sivakumar Shivan , Gollins Simon , Tran Nhan L. , Dhruv Harshil D. , Berens Michael E. , Bryce Alan , Sekulic Aleksandar , Ribas Antoni , Trent Jeffrey M. , LoRusso Patricia M. , Murtaza Muhammed
Published: May 2018

Pre-analytical factors can significantly affect circulating cell-free DNA (cfDNA) analysis. However, there are few robust methods to rapidly assess sample quality and the impact of pre-analytical processing. To address this gap and to evaluate effects of DNA extraction methods and blood collection tubes on cfDNA yield and fragment size, we developed a multiplexed droplet digital PCR (ddPCR) assay with 5 short and 4 long amplicons targeting single copy genomic loci. Using this assay, we compared 7 cfDNA extraction kits and found cfDNA yield and fragment size vary significantly. We also compared 3 blood collection protocols using plasma samples from 23 healthy volunteers (EDTA tubes processed within 1 hour and Cell-free DNA Blood Collection Tubes processed within 24 and 72 hours) and found no significant differences in cfDNA yield, fragment size and background noise between these protocols. In 219 clinical samples, cfDNA fragments were shorter in plasma samples processed immediately after venipuncture compared to archived samples, suggesting contribution of background DNA by lysed peripheral blood cells. In summary, we have described a multiplexed ddPCR assay to assess quality of cfDNA samples prior to downstream molecular analyses and we have evaluated potential sources of pre-analytical variation in cfDNA studies.
Electrolytic ablation enables cancer cell targeting through pH modulation
Authors: Perkons Nicholas R. , Stein Elliot J. , Nwaezeapu Chike , Wildenberg Joseph C. , Saleh Kamiel , Itkin-Ofer Roni , Ackerman Daniel , Soulen Michael C. , Hunt Stephen J. , Nadolski Gregory J. , Gade Terence P.
Published: May 2018

Minimally invasive ablation strategies enable locoregional treatment of tumors. One such strategy, electrolytic ablation, functions through the local delivery of direct current without thermal effects, facilitating enhanced precision. However, the clinical application of electrolytic ablation is limited by an incompletely characterized mechanism of action. Here we show that acid and base production at the electrodes precipitates local pH changes causing the rapid cell death that underlies macroscopic tumor necrosis at pH > 10.6 or < 4.8. The extent of cell death can be modulated by altering the local buffering capacity and antioxidant availability. These data demonstrate that electrolytic ablation is distinguished from other ablation strategies via its ability to induce cellular necrosis by directly altering the tumor microenvironment. These findings may enable further development of electrolytic ablation as a curative therapy for primary, early stage tumors.
Alleviating luminescence concentration quenching in lanthanide doped CaF2 based nanoparticles through Na+ ion doping
Authors: Xu Bing , Li Dongyu , Huang Zhen , Tang Chunliang , Mo Wenhao , Ma Ying
Published: May 2018

Optimal doping concentration of Nd3+ shifts from 10 mol% to 30 mol% through Na+ doping, along with an ∼32 times NIR brightness increase.
Mechanism of H adatoms improving the O2 reduction reaction on the Zn-modified anatase TiO2 (101) surface studied by first principles calculation
Authors: Liu Liangliang , Li Chongyang , Jiang Man , Li Xiaodong , Huang Xiaowei , Wang Zhu , Jia Yu
Published: May 2018

Surface H and subsurface Zn interstitials could facilitate O2 adsorption and dissociation on the TiO2 surface.
Uranium(iii) complexes supported by hydrobis(mercaptoimidazolyl)borates: synthesis and oxidation chemistry
Authors: Maria Leonor , Santos Isabel C. , Santos Isabel
Published: May 2018

[UIIII{κ3-H(R)B(timMe)2}2(thf)2] (R = H, Ph) complexes have been prepared by the salt ligand metathesis reaction with [UI3(thf)4]. Oxidation reactions of the uranium(iii) complexes afforded the first structurally characterized U(iv) and U(vi) complexes supported by hydrobis(mercaptoimidazolyl)borates.