bluuebunny/crossref_metadata_2025 huggingface dataset:
Stepped care in primary care – guided self-help and face-to-face cognitive behavioural therapy for common mental disorders: a randomized controlled trial
Authors: Salomonsson Sigrid , Santoft Fredrik , Lindsäter Elin , Ejeby Kersti , Ljótsson Brjánn , Öst Lars-Göran , Ingvar Martin , Lekander Mats , Hedman-Lagerlöf Erik
Published: November 2017

Background

Common mental disorders (CMD) cause large suffering and high societal costs. Cognitive behavioural therapy (CBT) can effectively treat CMD, but access to treatment is insufficient. Guided self-help (GSH) CBT, has shown effects comparable with face-to-face CBT. However, not all patients respond to GSH, and stepping up non-responders to face-to-face CBT, could yield larger response rates. The aim was to test a stepped care model for CMD in primary care by first evaluating the effects of GSH-CBT and secondly, for non-responders, evaluating the additional effect of face-to-face CBT.

Methods

Consecutive patients (N = 396) with a principal disorder of depression, anxiety, insomnia, adjustment or exhaustion disorder were included. In Step I, all patients received GSH-CBT. In Step II, non-responders were randomized to face-to-face CBT or continued GSH. The primary outcome was remission status, defined as a score below a pre-established cutoff on a validated disorder-specific scale.

Results

After GSH-CBT in Step I, 40% of patients were in remission. After Step II, 39% of patients following face-to-face CBT were in remission compared with 19% of patients after continued GSH (p = 0.004). Using this stepped care model required less than six therapy sessions per patient and led to an overall remission rate of 63%.

Conclusions

Stepped care can be effective and resource-efficient to treat CMD in primary care, leading to high remission rates with limited therapist resources. Face-to-face CBT speeded up recovery compared with continued GSH. At follow-ups after 6 and 12 months, remission rates were similar in the two groups.
Constructing contempt
Authors: Spring Victoria L. , Cameron C. Daryl , Gray Kurt , Lindquist Kristen A.
Published: November 2017

Gervais & Fessler argue that contempt is a natural kind and that its experience cannot be explained by a constructionist account of emotion. We dispute these claims and offer a positive constructionist model of contempt that accounts for the existing evidence and unifies conflicting findings in the literature on contempt.
Warmth and competence as distinct dimensions of value in social emotions
Authors: Cikara Mina
Published: November 2017

Gervais & Fessler's analysis collapses across two orthogonal dimensions of social value to explain contempt: relational value, predicted by cooperation, and agentic value, predicted by status. These dimensions interact to potentiate specific social emotions and behaviors in intergroup contexts. By neglecting the unique roles of these dimensions – and their associated attributes: warmth and competence – the sentiment framework cedes predictive precision.
Deep mechanisms of social affect – Plastic parental brain mechanisms for sensitivity versus contempt
Authors: Swain James E. , Ho S. Shaun
Published: November 2017

Insensitive parental thoughts and affect, similar to contempt, may be mapped onto a network of basic emotions moderated by attitudinal representations of social-relational value. Brain mechanisms that reflect emotional valence of baby signals among parents vary according to individual differences and show plasticity over time. Furthermore, mental health problems and treatments for parents may affect these brain systems toward or away from contempt, respectively.
Self-focusing of asymmetric cosh-Gaussian laser beams propagating through collisionless magnetized plasma
Authors: Vhanmore B. D. , Patil S. D. , Valkunde A. T. , Urunkar T. U. , Gavade K. M. , Takale M. V.
Published: November 2017

In this paper, self-focusing of asymmetric cosh-Gaussian laser beams in collisionless magnetized plasma has been studied. The non-linearity in dielectric constant considered herein is mainly due to the ponderomotive force. The non-linear coupled differential equations for the beam width parameters in transverse dimensions of the beam have been obtained by using WKB and paraxial approximations under parabolic equation approach. The numerical computation is completed by using fourth-order Runge–Kutta method. The effect of unlike decentered parameters in both transverse dimensions of the beam on self-focusing of cosh-Gaussian beams has been presented. Further, the effect of the static magnetic field and polarization modes of the laser has been explored.
Strong electromagnetic pulses generated in high-intensity short-pulse laser interactions with thin foil targets
Authors: Rączka P. , Dubois J.-L. , Hulin S. , Tikhonchuk V. , Rosiński M. , Zaraś-Szydłowska A. , Badziak J.
Published: November 2017

Measurements are reported of the target neutralization current, the target charge, and the tangential component of the magnetic field generated as a result of laser–target interaction by pulses with the energy in the range of 45–92 mJ on target and the pulse duration from 39 to 1000 fs. The experiment was performed at the Eclipse facility in CELIA, Bordeaux. The aim of the experiment was to extend investigations performed for the thick (mm scale) targets to the case of thin (μm thickness) targets in a way that would allow for a straightforward comparison of the results. We found that thin foil targets tend to generate 20–50% higher neutralization current and the target charge than the thick targets. The measurement of the tangential component of the magnetic field had shown that the initial spike is dominated by the 1 ns pulse consistent with the 1 ns pulse of the neutralization current, but there are some differences between targets of different types on sub-ns scale, which is an effect going beyond a simple picture of the target acting as an antenna. The sub-ns structure appears to be reproducible to surprising degree. We found that there is in general a linear correlation between the maximum value of the magnetic field and the maximum neutralization current, which supports the target-antenna picture, except for pulses 100s of fs long.
JIVE FOR PANEL DYNAMIC SIMULTANEOUS EQUATIONS MODELS
Authors: Hsiao Cheng , Zhou Qiankun
Published: November 2017

We consider the method of moments estimation of a structural equation in a panel dynamic simultaneous equations model under different sample size combinations of cross-sectional dimension,N, and time series dimension,T. Two types of linear transformation to remove the individual-specific effects from the model, first difference and forward orthogonal demeaning, are considered. We show that the Alvarez and Arellano (2003) type GMM estimator under both transformations is consistent only if${T \over N} \to 0$as$\left( {N,T} \right) \to \infty $. However, it is asymptotically biased if${{{T^3}} \over N} \to \kappa \ne 0 < \infty$as$\left( {N,T} \right) \to \infty $. Since the validity of statistical inference depends critically on whether an estimator is asymptotically unbiased, we suggest a jackknife bias reduction method and derive its limiting distribution. Monte Carlo studies are conducted to demonstrate the importance of using an asymptotically unbiased estimator to obtain valid statistical inference.
ROLE OF THE EMOTIONS AND CLASSROOM ENVIRONMENT IN WILLINGNESS TO COMMUNICATE
Authors: Khajavy Gholam Hassan , MacIntyre Peter D. , Barabadi Elyas
Published: November 2017

The purpose of the present study was to examine the relations between emotions, classroom environment, and willingness to communicate (WTC) using the advanced quantitative methodological procedure of doubly latent multilevel analysis. To this end, 1528 secondary school students from 65 different classrooms in Iran participated in the study. Results of the doubly latent multilevel analysis showed that a positive classroom environment is related to fostering WTC and enjoyment, while it reduces anxiety among students. Moreover, enjoyment was found as an important factor in increasing WTC at both student and classroom level, while anxiety reduced WTC only at the student level. Finally, the results of the study are discussed and pedagogical implications are provided for language teachers.
Discounting and intragenerational equity
Authors: Emmerling Johannes
Published: November 2017

We study the social discount rate, taking into account inequality within generations, that is, across countries or individuals. We show that if inequality decreases over time, the social discount rate should be lower than the one obtained by the standard Ramsey rule under certain but reasonable conditions. Applied to the global discount rate and due to the projected convergence across countries, this implies that the inequality adjusted discount rate should be about twice as high as the standard Ramsey rule predicts. For individual countries on the other hand, where inequality tends to increase over time, the effect goes in the other direction. For the United States for instance, this inequality effect leads to a reduction of the social discount rate by about 0.5 to 1 percentage points. We also present an analytical formula for the social discount rate allowing us to disentangle inequality, risk, and intertemporal fluctuation aversion.
Integrated risk management for defined benefit pension schemes: a practical guide
Authors: Hitchcox A. N. , Patel C. , Ramsey C. J. , Studd E. L. , Ma L. T. , Elliott M. B. , Keogh T. W.
Published: November 2017

The Working Party has developed some practical hints and tips for those developing integrated risk management (IRM) plans for UK defined benefit pension schemes in the context of the requirements of the Pensions Regulator. Four case studies are presented to illustrate its conclusions, which are encapsulated in the ten commandments for effective IRM. IRM is the consideration of investment, funding and covenant issues, and how these interact. Its purpose should be to aid decision making and so should have a clear outcome in mind. It should be a continuous process and should form part of everyday trustee governance – it is not simply a one-off exercise. Whilst most Trustees and advisors consider funding issues when setting their investment strategy and vice versa, fewer fully integrate covenant into their decision-making process. However, covenant underpins all risk taken in a pension scheme and so needs to form a regular part of trustee discussions and analysis by advisors.
RELATIVE CYCLES WITH MODULI AND REGULATOR MAPS
Authors: Binda Federico , Saito Shuji
Published: November 2017

Let$\overline{X}$be a separated scheme of finite type over a field$k$and$D$a non-reduced effective Cartier divisor on it. We attach to the pair$(\overline{X},D)$a cycle complex with modulus, those homotopy groups – called higher Chow groups with modulus – generalize additive higher Chow groups of Bloch–Esnault, Rülling, Park and Krishna–Levine, and that sheafified on$\overline{X}_{\text{Zar}}$gives a candidate definition for a relative motivic complex of the pair, that we compute in weight$1$. When$\overline{X}$is smooth over$k$and$D$is such that$D_{\text{red}}$is a normal crossing divisor, we construct a fundamental class in the cohomology of relative differentials for a cycle satisfying the modulus condition, refining El Zein’s explicit construction of the fundamental class of a cycle. This is used to define a natural regulator map from the relative motivic complex of$(\overline{X},D)$to the relative de Rham complex. When$\overline{X}$is defined over$\mathbb{C}$, the same method leads to the construction of a regulator map to a relative version of Deligne cohomology, generalizing Bloch’s regulator from higher Chow groups. Finally, when$\overline{X}$is moreover connected and proper over$\mathbb{C}$, we use relative Deligne cohomology to define relative intermediate Jacobians with modulus$J_{\overline{X}|D}^{r}$of the pair$(\overline{X},D)$. For$r=\dim \overline{X}$, we show that$J_{\overline{X}|D}^{r}$is the universal regular quotient of the Chow group of$0$-cycles with modulus.
Ultra compact multi-standard low-noise amplifiers in 28 nm CMOS with inductive peaking
Authors: Sobotta Elena , Belfiore Guido , Ellinger Frank
Published: November 2017

This work presents the design of two compact multi-standard low-noise amplifier (LNA) in a 28 nm low-power bulk CMOS process. The transistor parameters were optimized by the gm/ID method taking into account the parasitics and the behavior of highly scaled transistors. To cover the industrial science medical (ISM)-bands around 2.4 and 5.8 GHz, the WLAN band as well as the Ku band a bandwidth enhancement is required. Two versions of LNAs, one with vertical inductors and one with active inductors, are implemented and verified by measurements. The noise figure (NF) exhibits 4.2 dB for the LNA with active inductors and 3.5 dB for the LNA with vertical inductors. The voltage gain reaches 12.8 and 13.4 dB, respectively, with a 3 dB-bandwidth of 20 GHz. Both input referred 1-dB-compression points are higher than −12 dBm making the chips attractive for communication standards with high linearity requirements. The chips consume 53 mW DC power and the LNA with active inductors occupies a core area of only 0.0018 mm2, whereas the version with vertical inductors requires 0.021 mm2.
A low-cost wideband phase shifter for two-way mm-wave phased array antenna system
Authors: Al-Saedi Hussam , Abdel-Wahab Wael M. , Gigoyan Suren , Taeb Aidin , Safavi-Naeini Safieddin
Published: November 2017

This paper presents a wideband, low-cost, high-performance, and continuous phase shifter for millimeter-wave (mm-wave) phased array systems. Its operational principle is based on modifying the propagation mode of a grounded coplanar waveguide (GCPW) line by placing a high dielectric constant slab over the GCPW line. The propagation constant and hence the phase shift is varied by changing the air gap height between the GCPW line and the dielectric slab. As a proof of concept, a piezoelectric transducer is used to precisely control this air gap height. A printed circuit board-based phase shifter prototype has been designed, fabricated, and tested at two different frequency bands (19–21 and 28.5–30.5 GHz), which are the downlink and uplink bands, respectively, of the Ka-band two-way satellite communication system. A continuous and almost linear phase–voltage characteristic has been achieved experimentally with average phase shift variations 170° and 260° over the two bands, respectively. The footprint of the proposed phase shifter is 2.1 mm×3 mm, which is quite small and suitable for low-profile mm-wave applications. The average insertion losses over the two bands are <0.53 and 2.35 dB with very low variations±0.22 and ±0.35 dB, respectively.
Metformin ameliorates arsenic trioxide hepatotoxicity via inhibiting mitochondrial complex I
Authors: Ling Sunbin , Shan Qiaonan , Liu Peng , Feng Tingting , Zhang Xuanyu , Xiang Penghui , Chen Kangchen , Xie Haiyang , Song Penghong , Zhou Lin , Liu Jimin , Zheng Shusen , Xu Xiao
Published: November 2017

Arsenic trioxide (ATO) is a well-accepted chemotherapy agent in managing promyelocytic leukemia. ATO often causes severe health hazards such as hepatotoxicity, dermatosis, neurotoxicity, nephrotoxicity and cardiotoxicity. The production of reactive oxygen species, (ROS) play a significant role in ATO-induced hepatotoxicity. The oral hypoglycemic drug, metformin, is considered to be a potential novel agent for chemoprevention in the treatment of cancer. Moreover, metformin has also been shown to have hepatoprotective effects. In the present study, we demonstrated that metformin protected normal hepatocytes from ATO-induced apoptotic cell death in vitro and in vivo. Gene expression screening revealed that glucose metabolism might be related to the metformin-induced protective effect on ATO-treated AML12 cells. The metformin-promoted or induced glycolysis was not responsible for the protection of AML12 cells from ATO-induced apoptotic cell death. Instead, metformin increased the intracellular NADH/NAD+ ratio by inhibiting mitochondrial respiratory chain complex I, further decreasing the intracellular ROS induced by ATO. Treatment with low glucose or rotenone, a mitochondrial respiratory chain complex I inhibitor, also protected AML12 cells from ATO-induced apoptotic cell death. We show for the first time that metformin protects the hepatocyte from ATO by regulating the mitochondrial function. With its properties of chemoprevention, chemosensitization and the amelioration of liver damage, metformin has great prospects for clinical application other than type 2 diabetes mellitus (T2DM).
Epothilone B impairs functional recovery after spinal cord injury by increasing secretion of macrophage colony-stimulating factor
Authors: Mao Liang , Gao Wei , Chen Shurui , Song Ying , Song Changwei , Zhou Zipeng , Zhao Haosen , Zhou Kang , Wang Wei , Zhu Kunming , Liu Chang , Mei Xifan
Published: November 2017

The microtubule-stabilizing drug epothilone B (epoB) has shown potential value in the treatment of spinal cord injury (SCI) through diverse mechanisms. However, it remains elusive why a limited overall effect was observed. We aim to investigate the limiting factors underlying functional recovery promoted by epoB. The same SCI model treated by epoB was established as discussed previously. We used a cerebrospinal fluid (CSF) sample to assess the changes in cytokines in milieu of the SCI lesion site after epoB treatment. We then analyzed the source of cytokines, the state of microglia/macrophages/monocytes (M/Ms), and the recruitment of neutrophil in the lesion site by using the results of antibody array. Following these findings, we further evaluated the motor functional recovery caused by the reshaped microenvironment. Systemic administration of epoB significantly increased levels of several cytokines in the CSF of the rat SCI model; macrophage colony-stimulating factor (M-CSF) secreted by intact central nervous system (CNS) cells was one of the cytokines with increased levels. Along with epoB and other cytokines, M-CSF reshapes the SCI milieu by activating the microglias, killing bone marrow-derived macrophages, polarizing the M/M to M1 phenotype, and activating downstream cytokines to exacerbate the SCI injury, but it also increases the expression of neurotrophic factors. Anti-inflammatory therapy using a neutralizing antibody mix shows encouraging results. Usingin vivoexperiments, our findings indicate that epoB inhibits the SCI functional recovery in many ways by reshaping the milieu, which counteracts the therapeutic efficacy that led to the limited overall effectiveness.
RNA-sequencing-based comparative analysis of human hepatic progenitor cells and their niche from alcoholic steatohepatitis livers
Authors: Ceulemans An , Verhulst Stefaan , Van Haele Matthias , Govaere Olivier , Ventura Juan-Jose , van Grunsven Leo A , Roskams Tania
Published: November 2017

Hepatic progenitor cells (HPCs) are small cells with a relative large oval nucleus and a scanty cytoplasm situated in the canals of Hering that express markers of (immature) hepatocytes and cholangiocytes. HPCs are present in large numbers in alcoholic steatohepatitis (ASH), one of the leading causes of chronic liver disease. To date, the mechanisms responsible for proliferation and differentiation of human HPCs are still poorly understood and the role of HPCs in ASH development is unknown. In this study, we aimed to characterise human HPCs and their interactions with other cells through comparison, on both protein and RNA level, of HPC-enriched cell populations from adult human liver tissue using different isolation methods. Fresh human liver tissue was collected from ASH explant livers and HPC-enriched cell populations were obtained via four different isolation methods: side population (SP), epithelial cell adhesion molecule (EpCAM) and trophoblast antigen 2 (TROP-2) membrane marker isolation and laser capture microdissection. Gene expression profiles of fluorescent-activated cell-sorted HPCs, whole liver extracts and laser microdissected HPC niches were determined by RNA-sequencing. Immunohistochemical evaluation of the isolated populations indicated the enrichment of HPCs in the SP, EpCAM+ and TROP-2+ cell populations. Pathway analysis of the transcription profiles of human HPCs showed an enrichment and activation of known HPC pathways like Wnt/β-catenin, TWEAK and HGF. Integration of the HPC niche profile suggests autocrine signalling by HPCs (TNFα, PDGFB and VEGFA) as well as paracrine signalling from the surrounding niche cells including MIF and IGF-1. In addition, we identified IL-17 A signalling as a potentially novel pathway in HPC biology. In conclusion, we provide the first RNA-seq-based, comparative transcriptome analysis of isolated human HPCs from ASH patients and revealed active signalling between HPCs and their surrounding niche cells in ASH livers and suggest that HPCs can actively contribute to liver inflammation.
River-bed armouring as a granular segregation phenomenon
Authors: Ferdowsi Behrooz , Ortiz Carlos P. , Houssais Morgane , Jerolmack Douglas J.
Published: November 2017

River bed-load transport is a kind of dense granular flow, and such flows are known to segregate grains. While gravel-river beds typically have an “armoured” layer of coarse grains on the surface, which acts to protect finer particles underneath from erosion, the contribution of granular physics to river-bed armouring has not yet been investigated. Here we examine these connections in a laboratory river with bimodal sediment size, by tracking the motion of particles from the surface to deep inside the bed, and find that armour develops by two distinct mechanisms. Bed-load transport in the near-surface layer drives rapid, shear rate-dependent advective segregation. Creeping grains beneath the bed-load layer give rise to slow but persistent diffusion-dominated segregation. We verify these findings with a continuum phenomenological model and discrete element method simulations. Our experiments suggest that some river-bed armouring may be due to granular segregation from below—rather than fluid-driven sorting from above—while also providing new insights on the mechanics of segregation that are relevant to a wide range of granular flows.
Delivery of the gene encoding the tumor suppressor Sef into prostate tumors by therapeutic-ultrasound inhibits both tumor angiogenesis and growth
Authors: Mishel Sabrin , Shneyer Boris , Korsensky Lina , Goldshmidt-Tran Orit , Haber Tom , Machluf Marcelle , Ron Dina
Published: November 2017

Carcinomas constitute over 80% of all human cancer types with no effective therapy for metastatic disease. Here, we demonstrate, for the first time, the efficacy of therapeutic-ultrasound (TUS) to deliver a human tumor suppressor gene, hSef-b, to prostate tumors in vivo. Sef is downregulated in various human carcinomas, in a manner correlating with tumor aggressiveness. In vitro, hSef-b inhibited proliferation of TRAMP C2 cells and attenuated activation of ERK/MAPK and the master transcription factor NF-κB in response to FGF and IL-1/TNF, respectively. In vivo, transfection efficiency of a plasmid co-expressing hSef-b/eGFP into TRAMP C2 tumors was 14.7 ± 2.5% following a single TUS application. Repeated TUS treatments with hSef-b plasmid, significantly suppressed prostate tumor growth (60%) through inhibition of cell proliferation (60%), and reduction in blood vessel density (56%). In accordance, repeated TUS-treatments with hSef-b significantly inhibited in vivo expression of FGF2 and MMP-9. FGF2 is a known mitogen, and both FGF2/MMP-9 are proangiogenic factors. Taken together our results strongly suggest that hSef-b acts in a cell autonomous as well as non-cell autonomous manner. Moreover, the study demonstrates the efficacy of non-viral TUS-based hSef-b gene delivery approach for the treatment of prostate cancer tumors, and possibly other carcinomas where Sef is downregulated.
Fabrication of Subnanometer-Precision Nanopores in Hexagonal Boron Nitride
Authors: Gilbert S. Matt , Dunn Gabriel , Azizi Amin , Pham Thang , Shevitski Brian , Dimitrov Edgar , Liu Stanley , Aloni Shaul , Zettl Alex
Published: November 2017

We demonstrate the fabrication of individual nanopores in hexagonal boron nitride (h-BN) with atomically precise control of the pore shape and size. Previous methods of pore production in other 2D materials typically create pores with irregular geometry and imprecise diameters. In contrast, other studies have shown that with careful control of electron irradiation, defects in h-BN grow with pristine zig-zag edges at quantized triangular sizes, but they have failed to demonstrate production and control of isolated defects. In this work, we combine these techniques to yield a method in which we can create individual size-quantized triangular nanopores through an h-BN sheet. The pores are created using the electron beam of a conventional transmission electron microscope; which can strip away multiple layers of h-BN exposing single-layer regions, introduce single vacancies, and preferentially grow vacancies only in the single-layer region. We further demonstrate how the geometry of these pores can be altered beyond triangular by changing beam conditions. Precisely size- and geometry-tuned nanopores could find application in molecular sensing, DNA sequencing, water desalination, and molecular separation.
Frontal theta activation during motor synchronization in autism
Authors: Kawasaki Masahiro , Kitajo Keiichi , Fukao Kenjiro , Murai Toshiya , Yamaguchi Yoko , Funabiki Yasuko
Published: November 2017

Autism is characterized by two primary characteristics: deficits in social interaction and repetitive behavioral patterns. Because interpersonal communication is extremely complicated, its underlying brain mechanisms remain unclear. Here we showed that both characteristics can be explained by a unifying underlying mechanism related to difficulties with irregularities. To address the issues, we measured electroencephalographm during a cooperative tapping task, which required participants to tap a key alternately and synchronously with constant rhythmic a PC program, a variable rhythmic PC program, or a human partner. We found that people with autism had great difficulty synchronizing tapping behavior with others, and exhibited greater than normal theta-wave (6 Hz) activity in the frontal cortex during the task, especially when their partner behaved somewhat irregularly (i.e. a variable rhythmic PC program or a human partner). Importantly, the higher theta-wave activity was related to the severity of autism, not the performance on the task. This indicates that people with autism need to use intense cognition when trying to adapt to irregular behavior and can easily become overtaxed. Difficulty adapting to irregular behavior in others is likely related to their own tendencies for repetitive and regular behaviors. Thus, while the two characteristics of autism have been comprehended separately, our unifying theory makes understanding the condition and developing therapeutic strategies more tractable.
EXOSC10/Rrp6 is post-translationally regulated in male germ cells and controls the onset of spermatogenesis
Authors: Jamin Soazik P. , Petit Fabrice G. , Kervarrec Christine , Smagulova Fatima , Illner Doris , Scherthan Harry , Primig Michael
Published: November 2017

EXOSC10 is a catalytic subunit of the exosome that processes biologically active transcripts, degrades aberrant mRNAs and targets certain long non-coding RNAs (lncRNAs). The yeast orthologue Rrp6 is required for efficient growth and gametogenesis, and becomes unstable during meiosis. However, nothing is known about the localization, stability and function of EXOSC10 in the rodent male germline. We detect the protein in nucleoli and the cytoplasm of mitotic and meiotic germ cells, and find that it transiently associates with the XY body, a structure targeted by meiotic sex chromosome inactivation (MSCI). Finally, EXOSC10 becomes unstable at later stages of gamete development. To determine Exosc10’s meiotic function, we inactivated the gene specifically in male germ cells using cre recombinase controlled by Stra8 or Ddx4/Vasa promoters. Mutant mice have small testes, show impaired germ cell differentiation and are subfertile. Our results demonstrate that EXOSC10 is post-translationally regulated in germ cells, associate the protein with epigenetic chromosome silencing, and reveal its essential role in germ cell growth and development.
High Energy Conversion Efficiency with 3-D Micro-Patterned Photoanode for Enhancement Diffusivity and Modification of Photon Distribution in Dye-Sensitized Solar Cells
Authors: Yun Min Ju , Sim Yeon Hyang , Cha Seung I. , Seo Seon Hee , Lee Dong Y.
Published: November 2017

Dye sensitize solar cells (DSSCs) have been considered as the promising alternatives silicon based solar cell with their characteristics including high efficiency under weak illumination and insensitive power output to incident angle. Therefore, many researches have been studied to improve the energy conversion efficiency of DSSCs. However the efficiency of DSSCs are still trapped at the around 10%. In this study, micro-scale hexagonal shape patterned photoanode have proposed to modify light distribution of photon. In the patterned electrode, the appearance efficiency have been obtained from 7.1% to 7.8% considered active area and the efficiency of 12.7% have been obtained based on the photoanode area. Enhancing diffusion of electrons and modification of photon distribution utilizing the morphology of the electrode are major factors to improving the performance of patterned electrode. Also, finite element method analyses of photon distributions were conducted to estimate morphological effect that influence on the photon distribution and current density. From our proposed study, it is expecting that patterned electrode is one of the solution to overcome the stagnant efficiency and one of the optimized geometry of electrode to modify photon distribution. Process of inter-patterning in photoanode has been minimized.
Cellular information dynamics through transmembrane flow of ions
Authors: Gatenby Robert A. , Frieden B. Roy
Published: November 2017

We propose cells generate large transmembrane ion gradients to form information circuits that detect, process, and respond to environmental perturbations or signals. In this model, the specialized gates of transmembrane ion channels function as information detectors that communicate to the cell through rapid and (usually) local pulses of ions. Information in the ion “puffs” is received and processed by the cell through resulting changes in charge density and/or mobile cation (and/or anion) concentrations alter the localization and function of peripheral membrane proteins. The subsequent changes in protein binding to the membrane or activation of K+, Ca2+ or Mg2+-dependent enzymes then constitute a cellular response to the perturbation. To test this hypothesis we analyzed ion-based signal transmission as a communication channel operating with coded inputs and decoded outputs. By minimizing the Kullback-Leibler cross entropy $${{\boldsymbol{H}}}_{{\boldsymbol{K}}{\boldsymbol{L}}}({\boldsymbol{p}}||{\boldsymbol{q}})$$

H

K
L

(
p

|

|

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)
between concentrations of the ion species inside $${{\boldsymbol{p}}}_{{\boldsymbol{i}}}({\boldsymbol{t}}){\boldsymbol{,}}{\boldsymbol{i}}={\boldsymbol{1}},\ldots ,{\boldsymbol{N}}$$

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i

(
t
)
,
i
=
1
,
…
,
N
and outside $$\,{{\boldsymbol{q}}}_{{\boldsymbol{i}}}({\boldsymbol{t}})$$

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i

(
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the cell membrane, we find signal transmission through transmembrane ion flow forms an optimal Shannon information channel that minimizes information loss and maximizes transmission speed. We demonstrate the ion dynamics in neuronal action potentials described by Hodgkin and Huxley (including the equations themselves) represent a special case of these general information principles.
Sialidase inhibitors attenuate pulmonary fibrosis in a mouse model
Authors: Karhadkar Tejas R. , Pilling Darrell , Cox Nehemiah , Gomer Richard H.
Published: November 2017

Fibrosis involves increasing amounts of scar tissue appearing in a tissue, but what drives this is unclear. In fibrotic lesions in human and mouse lungs, we found extensive desialylation of glycoconjugates, and upregulation of sialidases. The fibrosis-associated cytokine TGF-β1 upregulates sialidases in human airway epithelium cells, lung fibroblasts, and immune system cells. Conversely, addition of sialidases to human peripheral blood mononuclear cells induces accumulation of extracellular TGF-β1, forming what appears to be a sialidase - TGF-β1 - sialidase positive feedback loop. Monocyte-derived cells called fibrocytes also activate fibroblasts, and we found that sialidases potentiate fibrocyte differentiation. A sialylated glycoprotein called serum amyloid P (SAP) inhibits fibrocyte differentiation, and sialidases attenuate SAP function. Injections of the sialidase inhibitors DANA and oseltamivir (Tamiflu) starting either 1 day or 10 days after bleomycin strongly attenuate pulmonary fibrosis in the mouse bleomycin model, and by breaking the feedback loop, cause a downregulation of sialidase and TGF-β1 accumulation. Together, these results suggest that a positive feedback loop involving sialidases potentiates fibrosis, and suggest that sialidase inhibitors could be useful for the treatment of fibrosis.
BOT-4-one attenuates NLRP3 inflammasome activation: NLRP3 alkylation leading to the regulation of its ATPase activity and ubiquitination
Authors: Shim Do-Wan , Shin Woo-Young , Yu Sang-Hyeun , Kim Byung-Hak , Ye Sang-Kyu , Koppula Sushruta , Won Hyung-Sik , Kang Tae-Bong , Lee Kwang-Ho
Published: November 2017

The ATPase activity of NLRP3 has pivotal role in inflammasome activation and is recognized as a good target for the development of the NLRP3 inflammasome-specific inhibitor. However, signals in the vicinity of the ATPase activity of NLRP3 have not been fully elucidated. Here, we demonstrate NLRP3 inflammasome-specific action of a benzoxathiole derivative, BOT-4-one. BOT-4-one exhibited an inhibition of NLRP3 inflammasome activation, which was attributable to its alkylating capability to NLRP3. In particular, the NLRP3 alkylation by BOT-4-one led to an impaired ATPase activity of NLRP3, thereby obstructing the assembly of the NLRP3 inflammasome. Additionally, we found that NLRP3 alkylators, including BOT-4-one, enhance the ubiquitination level of NLRP3, which might also contribute to the inhibition of NLRP3 inflammasome activation. Finally, BOT-4-one appeared to be superior to other known NLRP3 alkylators in inhibiting the functionality of the NLRP3 inflammasome and its resulting anti-inflammatory activity was confirmed in vivo using a monosodium urate-induced peritonitis mouse model. Collectively, the results suggest that NLRP3 alkylators function by inhibiting ATPase activity and increasing the ubiquitination level of NLRP3, and BOT-4-one could be the type of NLRP3 inhibitor that may be potentially useful for the novel development of a therapeutic agent in controlling NLRP3 inflammasome-related diseases.
Influenza virus segment 5 (+)RNA - secondary structure and new targets for antiviral strategies
Authors: Soszynska-Jozwiak Marta , Michalak Paula , Moss Walter N. , Kierzek Ryszard , Kesy Julita , Kierzek Elzbieta
Published: November 2017

Influenza A virus is a threat for humans due to seasonal epidemics and occasional pandemics. This virus can generate new strains that are dangerous through nucleotide/amino acid changes or through segmental recombination of the viral RNA genome. It is important to gain wider knowledge about influenza virus RNA to create new strategies for drugs that will inhibit its spread. Here, we present the experimentally determined secondary structure of the influenza segment 5 (+)RNA. Two RNAs were studied: the full-length segment 5 (+)RNA and a shorter construct containing only the coding region. Chemical mapping data combined with thermodynamic energy minimization were used in secondary structure prediction. Sequence/structure analysis showed that the determined secondary structure of segment 5 (+)RNA is mostly conserved between influenza virus type A strains. Microarray mapping and RNase H cleavage identified accessible sites for oligonucleotides in the revealed secondary structure of segment 5 (+)RNA. Antisense oligonucleotides were designed based on the secondary structure model and tested against influenza virus in cell culture. Inhibition of influenza virus proliferation was noticed, identifying good targets for antisense strategies. Effective target sites fall within two domains, which are conserved in sequence/structure indicating their importance to the virus.
Engineering DNA Backbone Interactions Results in TALE Scaffolds with Enhanced 5-Methylcytosine Selectivity
Authors: Rathi Preeti , Witte Anna , Summerer Daniel
Published: November 2017

Transcription activator-like effectors (TALEs) are DNA major-groove binding proteins widely used for genome targeting. TALEs contain an N-terminal region (NTR) and a central repeat domain (CRD). Repeats of the CRD selectively recognize each one DNA nucleobase, offering programmability. Moreover, repeats with selectivity for 5-methylcytosine (5mC) and its oxidized derivatives can be designed for analytical applications. However, both TALE domains also nonspecifically interact with DNA phosphates via basic amino acids. To enhance the 5mC selectivity of TALEs, we aimed to decrease the nonselective binding energy of TALEs. We substituted basic amino acids with alanine in the NTR and identified TALE mutants with increased selectivity. We then analysed conserved, DNA phosphate-binding KQ diresidues in CRD repeats and identified further improved mutants. Combination of mutations in the NTR and CRD was highly synergetic and resulted in TALE scaffolds with up to 4.3-fold increased selectivity in genomic 5mC analysis via affinity enrichment. Moreover, transcriptional activation in HEK293T cells by a TALE-VP64 construct based on this scaffold design exhibited a 3.5-fold increased 5mC selectivity. This provides perspectives for improved 5mC analysis and for the 5mC-conditional control of TALE-based editing constructs in vivo.
Impaired oxidative stress response characterizes HUWE1-promoted X-linked intellectual disability
Authors: Bosshard Matthias , Aprigliano Rossana , Gattiker Cristina , Palibrk Vuk , Markkanen Enni , Backe Paul Hoff , Pellegrino Stefania , Raymond F. Lucy , Froyen Guy , Altmeyer Matthias , Bjørås Magnar , Dianov Grigory L. , van Loon Barbara
Published: November 2017

Mutations in the HECT, UBA and WWE domain-containing 1 (HUWE1) E3 ubiquitin ligase cause neurodevelopmental disorder X-linked intellectual disability (XLID). HUWE1 regulates essential processes such as genome integrity maintenance. Alterations in the genome integrity and accumulation of mutations have been tightly associated with the onset of neurodevelopmental disorders. Though HUWE1 mutations are clearly implicated in XLID and HUWE1 regulatory functions well explored, currently much is unknown about the molecular basis of HUWE1-promoted XLID. Here we showed that the HUWE1 expression is altered and mutation frequency increased in three different XLID individual (HUWE1 p.R2981H, p.R4187C and HUWE1 duplication) cell lines. The effect was most prominent in HUWE1 p.R4187C XLID cells and was accompanied with decreased DNA repair capacity and hypersensitivity to oxidative stress. Analysis of HUWE1 substrates revealed XLID-specific down-regulation of oxidative stress response DNA polymerase (Pol) λ caused by hyperactive HUWE1 p.R4187C. The subsequent restoration of Polλ levels counteracted the oxidative hypersensitivity. The observed alterations in the genome integrity maintenance may be particularly relevant in the cortical progenitor zones of human brain, as suggested by HUWE1 immunofluorescence analysis of cerebral organoids. These results provide evidence that impairments of the fundamental cellular processes, like genome integrity maintenance, characterize HUWE1-promoted XLID.
Production and Purification of Filovirus Glycoproteins in Insect and Mammalian Cell Lines
Authors: Clarke Elizabeth C. , Collar Amanda L. , Ye Chunyan , Caì Yíngyún , Anaya Eduardo , Rinaldi Derek , Martinez Britney , Yarborough Sarah , Merle Christine , Theisen Manfred , Wada Jiro , Kuhn Jens H. , Bradfute Steven B.
Published: November 2017

Filoviruses are highly virulent pathogens capable of causing severe disease. The glycoproteins of filoviruses are the only virally expressed proteins on the virion surface and are required for receptor binding. As such, they are the main candidate vaccine antigen. Despite their virulence, most filoviruses are not comprehensively characterized, and relatively few commercially produced reagents are available for their study. Here, we describe two methods for production and purification of filovirus glycoproteins in insect and mammalian cell lines. Considerations of expression vector choice, modifications to sequence, troubleshooting of purification method, and glycosylation differences are all important for successful expression of filovirus glycoproteins in cell lines. Given the scarcity of commercially available filovirus glycoproteins, we hope our experiences with possible difficulties in purification of the proteins will facilitate other researchers to produce and purify filovirus glycoproteins rapidly.
Gender composition mediates social facilitation effect in co-action condition
Authors: Liu Na , Yu Ruifeng , Yang Lindong , Lin Xuelian
Published: November 2017

Working with co-actors is a common work-organization mode. Whether the presence of opposite-sex co-actors (OCs) can induce social facilitation effect and how an actor’s performance is influenced by the gender composition of co-actors remain unknown. The present study aims to examine the influence of the gender composition of co-actors on the intensity of the social facilitation effect. In Experiment 1, participants performed visual search tasks alone and in six co-action conditions with varying gender compositions. In Experiment 2, the participants performed modular arithmetic tasks in three conditions with electroencephalogram activity recorded and salivary cortisol measured: alone, with a same-sex co-actor (SC), and with an OC. Results indicated that the social facilitation effect was stronger in the presence of OCs than in the presence of only SCs. The intensities of social facilitation effect resulting from the varying gender composition of co-actors were obtained and compared. A participant’s power of alpha band was lower, whereas power of beta band and normalised cortisol level were higher in the presence of an OC than in the presence of an SC. These findings provide insights into the influencing mechanisms of gender composition on the intensity of the social facilitation effect in the co-action condition.
Hypochlorite degrades 2D graphene oxide sheets faster than 1D oxidised carbon nanotubes and nanohorns
Authors: Newman Leon , Lozano Neus , Zhang Minfang , Iijima Sumio , Yudasaka Masako , Bussy Cyrill , Kostarelos Kostas
Published: November 2017

Carbon nanostructures are currently fuelling a revolution in science and technology in areas ranging from aerospace engineering to electronics. Oxidised carbon nanomaterials, such as graphene oxide, exhibit dramatically improved water dispersibility compared to their pristine equivalents, allowing their exploration in biology and medicine. Concomitant with these potential healthcare applications, the issue of degradability has been raised and has started to be investigated. The aim of the present study was to assess the potential of hypochlorite, a naturally occurring and industrially used ion, to degrade oxidised carbon nanomaterials within a week. Our main focus was to characterise the physical and chemical changes that occur during degradation of graphene oxide compared to two other oxidised carbon nanomaterials, namely carbon nanotubes and carbon nanohorns. The kinetics of degradation were closely monitored over a week using a battery of techniques including visual observation, UV–Vis spectroscopy, Raman spectroscopy, infra-red spectroscopy, transmission electron microscopy and atomic force microscopy. Graphene oxide was rapidly degraded into a dominantly amorphous structure lacking the characteristic Raman signature and microscopic morphology. Oxidised carbon nanotubes underwent degradation via a wall exfoliation mechanism, yet maintained a large fraction of the sp2 carbon backbone, while the degradation of oxidised carbon nanohorns was somewhat intermediate. The present study shows the timeline of physical and chemical alterations of oxidised carbon nanomaterials, demonstrating a faster degradation of 2D graphene oxide sheets compared to 1D oxidised carbon nanomaterials over 7 days in the presence of an oxidising species.
Acceleration of metal–ligand complexation kinetics by electrospray ionization
Authors: Kelley Morgan P. , Davis Austen , Clowers Brian , Clark Aurora E. , Clark Sue B.
Published: November 2017

Electrospray ionization mass spectrometry (ESI-MS) is demonstrated to significantly accelerate the kinetics of metal–ligand complexation, with the formation rate constant increasing by more than an order of magnitude over previously determined solution-phase values.
Highly efficient hydrogen evolution electrocatalysts based on coupled molybdenum phosphide and reduced graphene oxide derived from MOFs
Authors: Li Ji-Sen , Sha Jing-Quan , Du Bing , Tang Bo
Published: November 2017

A coupled hybrid of molybdenum phosphide and reduced graphene oxide has been synthesized utilizing Mo-based MOFs as precursors through a facile method for the first time. The nanocomposite exhibits superior electrocatalytic performance, which is one of the best MoP-based electrocatalysts under acidic conditions reported so far.
Photoinduced, copper-catalyzed three components cyanofluoroalkylation of alkenes with fluoroalkyl iodides as fluoroalkylation reagents
Authors: Guo Quanping , Wang Mengran , Wang Yanfang , Xu Zhaoqing , Wang Rui
Published: November 2017

Under UV light irradiation, the Cu-catalyzed cyanofluoroalkylation of alkenes was realized by directly using fluoroalkyl iodides as fluoroalkylation reagents.
Imaging cellular trafficking processes in real time using lysosome targeted up-conversion nanoparticles
Authors: Pramanik Sumit Kumar , Sreedharan Sreejesh , Singh Harwinder , Green Nicola H. , Smythe Carl , Thomas Jim. A. , Das Amitava
Published: November 2017

Peptide conjugated upconverting nanoparticles for specific imaging of lysosome
A hierarchically structured anatase-titania/indium-tin-oxide nanocomposite as an anodic material for lithium-ion batteries
Authors: Luo Yan , Zhang Yiming , Huang Jianguo
Published: November 2017

A nanotubular titania/ITO nanocomposite is synthesized, exhibiting enhanced electrochemical performance as an anodic material for lithium-ion batteries.
Selective MeCN/EtCN sorption and preferential inclusion of substituted benzenes in a cage structure with arylsulfonamide-armed anthraquinones
Authors: Takeda Takashi , Noro Shin-ichiro , Nakamura Takayoshi , Suzuki Yasutaka , Kawamata Jun , Akutagawa Tomoyuki
Published: November 2017

The titled compounds 1,4 formed low-dimensional crystal structures with selective sorption/inclusion properties.
Mechanistic insights on ethanol dehydrogenation on Pd–Au model catalysts: a combined experimental and DFT study
Authors: Evans E. J. , Li H. , Yu Wen-Yueh , Mullen G. M. , Henkelman G. , Mullins C. Buddie
Published: November 2017

UHV experiments and DFT show the dependence of the ethanol dehydrogenation mechanism on the Pd ensemble size on Au(111).
Calcium-dependent hydrolysis of supported planar lipids was triggered by honey bee venom phospholipase A2with the right orientation at the interface
Authors: Kai Siqi , Li Xu , Li Bolin , Han Xiaofeng , Lu Xiaolin
Published: November 2017

Hydrolysis of planar phospholipids catalyzed by honey bee venom phospholipase A2(bvPLA2) was studied.
Electron spin fluctuation in intense laser fields
Authors: Korani Youssef , Sabzyan Hassan
Published: November 2017

Spin fluctuation dynamics of diatomic and monoatomic ions interacting with ultrashort intense laser pulses is studied by solving the time-dependent Dirac equation.