bluuebunny/crossref_metadata_2025 huggingface dataset:
Conductive inks based on methacrylate end‐capped poly(3,4‐ethylenedioxythiophene) for printed and flexible electronics
Authors: Sabatini V. , Farina H. , Ortenzi M.A.
Published: January 2017

A new synthesis of methacrylate end‐capped poly(3,4‐ethylenedioxythiophene) (PEDOT) was performed: the polymer is soluble in common organic solvents, thus overcoming the well‐known technical problems related to the use of commercial PEDOT in different printing technologies, such as screen printing, due to its poor processability and compatibility in formulations with other resins and polymers. The new synthetic method developed is based on the direct oxidative polycondensation of 3,4‐ethylenedioxythiophene (EDOT) in the presence of an oxidant species and a crosslinkable end‐capper, i.e., methacrylate end‐capped EDOT (mEDOT), prepared via Friedel Crafts acylation with methacryloyl chloride. The oxidative polycondensation between EDOT and mEDOT monomers in the presence of a new kind of doping agent, Sulfonated Polyarylethersulfone (SPES)—characterized by different degree of sulfonation (DS)—was conducted, leading to functional end‐capped conducting PEDOT (mPEDOT_SPES), with conductivity of 210 S/cm, 50 S/cm higher than the one of commercial PEDOT. Thanks to the enhancement of solubility, leading to better processability, end‐capped PEDOTs were formulated with a thermoplastic ink, Plastisol®, and electronic circuits were successfully screen printed on flexible cotton substrates, to obtain printed crosslinkable electronic circuits. The conductive features of mPEDOT_SPESs were successfully compared with the ones of PEDOT and of not‐doped end‐capped PEDOTs. POLYM. ENG. SCI., 57:491–501, 2017. © 2017 Society of Plastics Engineers
Quantitative proteomic analysis of HIV‐1 Tat‐induced dysregulation in SH‐SY5Y neuroblastoma cells
Authors: Ganief Tariq , Gqamana Putuma , Garnett Shaun , Hoare Jackie , Stein Dan J. , Joska John , Soares Nelson , Blackburn Jonathan M.
Published: January 2017

Despite affecting up to 70% of HIV‐positive patients and being the leading cause of dementia in patients under 40 years, the molecular mechanisms involved in the onset of HIV‐associated neurocognitive disorders (HAND) are not well understood. To address this, we performed SILAC‐based quantitative proteomic analysis on HIV‐Tat treated SH‐SY5Y neuroblastoma cells. Isolated protein was fractionated by SDS‐PAGE and analyzed by nLC‐MS/MS on an Orbitrap Velos. Using MaxQuant, we identified and quantified 3077 unique protein groups, of which 407 were differentially regulated. After applying an additional standard deviation‐based cutoff, 29 of these were identified as highly significantly and stably dysregulated. GO term analysis shows dysregulation in both protein translation machinery as well as cytoskeletal regulation that have both been implicated in other dementias. In addition, several key cytoskeletal regulatory proteins such as ARHGEF17, the Rho GTPase, SHROOM3, and CMRP1 are downregulated. Together, these data demonstrate that HIV‐Tat can dysregulate neuronal cytoskeletal regulatory proteins that could lead to the major HAND clinical manifestation‐synapse loss.
Continuous‐time Kalman filtering on the orthogonal group O(n)
Authors: de Ruiter Anton H. J. , Forbes James Richard
Published: January 2017

This paper presents a continuous‐time O(n)‐constrained Kalman‐like filter. O(n) is the group of n × n orthonormal matrices. The O(n)‐constrained Kalman‐like filter is derived by posing a constrained optimization problem. The solution involves a projection of the unconstrained Kalman state estimate derivative onto the tangent space of O(n). Using this filter, an extended O(n)‐constrained Kalman‐like filter is developed for nonlinear systems where a portion of the states evolve on O(n). A numerical example demonstrates the effectiveness of the extended O(n)‐constrained Kalman‐like filter. Copyright © 2017 John Wiley & Sons, Ltd.
Measuring the risk value of sensitive dataflow path in Android applications
Authors: Feng Pengbin , Sun Cong , Ma Jianfeng
Published: January 2017

Nowadays, smartphones carry large amounts of user privacy and sensitive data. With the popularity of the Android operating system, the cases of sensitive date leakage in Android applications are on the rise and are causing a great loss to Android users. In order to mitigate this condition, static and dynamic taint analysis are applied to precisely detect sensitive data leakages. These approaches cannot distinguish sensitive data leakages in benign apps from the ones in malicious apps. Recently, the difference on sensitive data flows between benign apps and malicious apps has been found to be significant. In this paper, we further find that there exists great difference between benign and malicious apps on the frequencies of sensitive dataflow paths. This difference can be used to enforce a risk value over every sensitive dataflow path. This risk value can guide the identification of sensitive data leakages in malicious apps. We present RISKPATH, a tool that automatically calculates the risk values for sensitive dataflow paths in Android applications. Applying the result of RISKPATH to MUDFLOW framework, we increase the true positive rate of malware detection by 3.96–6.54% on different datasets with reasonable increase in time and memory consumption. Copyright © 2017 John Wiley & Sons, Ltd.
Well Known or Well Liked? The Effects of Corporate Reputation on Firm Value at the Onset of a Corporate Crisis
Authors: Wei Jiuchang , Ouyang Zhe , Chen Haipeng (Allan)
Published: January 2017

Research summary: We study how two dimensions of reputation (i.e., generalized favorability and being known) and attribution of crisis responsibility affect firm value at the onset of a crisis. Analyzing 126 corporate crises befalling publicly listed firms in China from 2008 to 2014, we find that generalized favorability serves as a buffer, while being known can be a burden, in influencing firm value. We also find that the buffering effect of generalized favorability is stronger when the attribution of crisis responsibility is low (vs. high). In addition, there is a negative interaction effect between the two dimensions of reputation such that the buffering effect of generalized favorability weakens when firms are better known. We discuss our contributions to research on corporate reputation and crisis management.

Managerial summary: Corporate reputation is an intangible asset, especially at the onset of a corporate crisis. This research sheds light on the “double‐edged sword” of corporate reputation by examining the effects of two reputation dimensions (i.e., being liked and being known) on firm value. Our results suggest that well‐liked firms can leverage their generalized favorability among stakeholders to assuage firm value loss, whereas well‐known firms may have to better communicate with stakeholders to overcome the burden of stakeholders' attention that escalates firm value loss. To better cope with the onset of a crisis, firms should therefore enhance their generalized favorability and simultaneously avert stakeholders' excessive attention. In addition, well‐liked firms can further buffer against the loss in firm value by reducing the perceived intentionality of a crisis. Copyright © 2017 John Wiley & Sons, Ltd.
Entry into Nascent Industries: Disentangling a Firm's Capability Portfolio at the Time of Investment Versus Market Entry
Authors: Moeen Mahka
Published: January 2017

Research summary: This article examines the capability antecedents of firm entry into nascent industries. Because a firm's technological investments in nascent industries typically occur before market entry, this study makes a distinction between firm capabilities at the time of market entry and at the time of initial investment. At the time of market entry, core technical capabilities and complementary assets influence the likelihood of entry. However, at the time of investment, a firm's integrative capabilities as well as the initial stocks of related technical capabilities and complementary assets become critical, as they enable endogenous development of core technical capabilities and complementary assets by the time of entry. The empirical sample consists of firms involved in field experiments in agricultural biotechnology during the period 1980–2010.

Managerial summary: New product commercialization in a nascent industry typically requires access to not only core technologies of the focal industry, but also supporting commercialization assets. However, firms may not possess these critical capabilities when they first invest in the industry. Instead, empirical evidence from the context of agricultural biotechnology shows that at the time of first investment, a firm's integrative capabilities partly explain their likelihood of entry. Integrative capabilities encompass a set of practices that enable effective coordination and communication, and in turn put firms in an advantageous position to develop the needed capabilities by the time of entry. Copyright © 2017 John Wiley & Sons, Ltd.
Concise Review: Regeneration in Mammalian Cochlea Hair Cells: Help from Supporting Cells Transdifferentiation
Authors: Franco Bénédicte , Malgrange Brigitte
Published: January 2017

It is commonly assumed that mammalian cochlear cells do not regenerate. Therefore, if hair cells are lost following an injury, no recovery could occur. However, during the first postnatal week, mice harbor some progenitor cells that retain the ability to give rise to new hair cells. These progenitor cells are in fact supporting cells. Upon hair cells loss, those cells are able to generate new hair cells both by direct transdifferentiation or following cell cycle re-entry and differentiation. However, this property of supporting cells is progressively lost after birth. Here, we review the molecular mechanisms that are involved in mammalian hair cell development and regeneration. Manipulating pathways used during development constitute good candidates for inducing hair cell regeneration after injury. Despite these promising studies, there is still no evidence for a recovery following hair cells loss in adult mammals.
Identifying the Biphasic Role of Calcineurin/NFAT Signaling Enables Replacement of Sox2 in Somatic Cell Reprogramming
Authors: Khodeer Sherif , Era Takumi
Published: January 2017

Induction of pluripotency with defined factors (octamer-binding transcription factor 4 [Oct4], SRY (sex determining region Y)-box 2 [Sox2], Kruppel-like factor 4 [Klf4], c-Myc) raises hopes for successful clinical trials. Despite considerable efforts, the molecular mechanism of reprogramming remains poorly understood. The aim of the present study was to identify the role of calcineurin/nuclear factor of activated T cells (NFAT) in reprogramming. Our results demonstrated a biphasic role for calcineurin/NFAT signaling during reprogramming. In the early phase of reprogramming, calcineurin activity is required to maintain proper cell cycle division and for mesenchymal–epithelial transition. In the late phase, calcineurin exerts a negative effect that is mediated by NFATc2. NFATc2 interacts with Hdac3, Ezh2, and Suv39h1 to increase H3K9me3 and H3K27me3 over the Sox2 enhancer and Klf2 promoter, respectively, resulting in the downregulation of their expression. Moreover, Gαq was identified as a positive upstream regulator for calcineurin. The Gαq/calcineurin/NFATc2 axis negatively regulates the late step of reprogramming. By inhibiting NFATc2 or calcineurin, induced pluripotent stem cells could be established without exogenous Sox2. Thus, the present study revealed another regulatory level of reprogramming, and proposes a biological axis that could be useful for cancer therapy.
Strategic resources: a missing role in understanding integration speed in international acquisition
Authors: Wei Tian , Clegg Jeremy
Published: January 2017

It has long been debated whether integration speed positively or negatively contributes to acquisition performance. Drawing on the resource‐based view, this study addresses this controversy in the literature by investigating how integration speed for specific categories of strategic resources affects the integration process by capturing the expected value of an acquisition. With six in‐depth case studies, it concludes that the relationship between integration speed and acquisition performance cannot be understood quantitatively; instead, the focus should be on the interaction between integration speed and three broad groups of strategic resources (managerial, customer‐oriented, and supplier‐oriented) post acquisition. The study further finds that the understanding of integration speed should not be from a stand‐alone viewpoint but rather from a dynamic perspective—a viewpoint combined with time of integration. The findings of this study also complement the existing understanding of integration by extending the knowledge of task integration and its interaction with human integration. © 2017 Wiley Periodicals, Inc.
Effects of Collagen Crosslink Augmentation on Mechanism of Compressive Load Sharing in Intervertebral Discs
Authors: Hedman Thomas P. , Chen Weng-Pin , Lin Leou-Chyr , Lin Hsiu-Jen , Chuang Shih-Youeng
Published: January 2017

Exogenous crosslinking has been shown to have potential for treating disc degeneration and back pain due to its ability to increase the strength and toughness of the annulus fibrosus, increase intervertebral joint stability, decrease intradiscal pressure, and increase fluid flow through the disc. Some results imply that crosslink augmentation may also lead to changes in the compressive load sharing properties of the disc. The objective of the present study was to evaluate directional stress distribution changes of the disc following genipin crosslinking treatment. Bovine lumbar motion segments were randomly divided into control and crosslinked groups. Annular strains were determined from simultaneous deformation measurements at various time points during compressive creep testing. Four stress components of the annulus were then calculated according to the previously measured modulus data. Immediately after the application of a 750-N compressive load, mean axial and radial compressive stresses in the crosslinked group were twofold higher than control means. Conversely, mean lamellae-aligned and circumferential tensile stresses of the crosslinked discs were 8- and threefold lower, respectively, compared to control means. After 1-h creep loading, the two compressive mean stresses in both the control and genipin-crosslinked specimens increased approximately threefold from their initial 750-N-loaded values. The two tensile mean stresses in the crosslinked group remained lower than the respective levels of the control means after creep loading. A greater proportion of annular compressive load support under compressive creep loading, with a commensurate decrease in both tensile stresses and strains, was seen in the discs following exogenous crosslink augmentation.
A photo voice perspective on factors contributing to the resilience of HIV positive Yoruba adolescent girls in Nigeria
Authors: Adegoke Catherine O. , Steyn Miemsie G.
Published: January 2017

There is a growing discourse worldwide on the impact of the Human Immunodeficiency Virus (HIV) on “at risk youths”. In response, five HIV‐positive Nigerian adolescent girls were qualitatively investigated in collaboration with a non‐governmental organisation (NGO) in Ibadan, an urban settlement in Nigeria in 2013. Using a secondary data analysis from a photo voice component of the research, combined with narratives, we show that participants possess the capacity to overcome their adversities from the effects of HIV infection and remain resilient. Few studies have used photovoice − a visual participatory approach − and its impact on this group. The theories of Bourdieu, Piaget and Erikson were used as tools to interpret and document, resilience, social capital and coping among participants. Findings reveal participants frame positive goals, use social competence, coping skills, and express personal challenges. These have serious implications for policy makers, researchers and programmer in strengthening adolescents' resilience.
Delayed treatment of 6‐Bromoindirubin‐3′‐oxime stimulates neurogenesis and functional recovery after focal ischemic stroke in mice
Authors: Wang Li‐Li , Li Jimei , Gu Xiaohuan , Wei Ling , Yu Shan Ping
Published: January 2017

Glycogen synthase kinase 3β (GSK3β) was originally identified as a regulator for glycogen metabolism and is now an important therapeutic target for a variety of brain disorders including neurodegenerative diseases due to it's pivotal role in cellular metabolism, proliferation and differentiation. In the development of stroke therapies focusing on tissue repair and functional recovery, promoting neurogenesis is a main approach in regenerative medicine. In the present investigation, we explored the effects of a GSK3β specific inhibitor, 6‐Bromoindirubin‐3′‐oxime (BIO), on regenerative activities of neuroblasts in the subventricular zone (SVZ) and functional recovery after focal cerebral ischemia. Adult C57/BL mice were subjected to occlusion of distal branches of middle cerebral artery (MCA) supplying the sensorimotor barrel cortex. Three days later, BIO (8.5 μg/kg, i.p.) was administered every 2 days until sacrificed at 14 or 21 days after stroke. The BIO treatment significantly increased generation of neuroblasts labeled with BrdU and BrdU/doublecortin (DCX) in the SVZ. Comparing to vehicle controls, increased number of neuroblasts migrated to the peri‐infarct region where they differentiate into mature neurons. Along with the elevated BDNF expression at the peri‐infarct area, the number of newly formed neurons was significantly increased. BIO treatment significantly enhanced sensorimotor functional recovery after the focal ischemia. It is suggested that the GSK3 signaling may be a potential therapeutic target for regenerative treatment after ischemic stroke.
Rebelocracy
Authors: Arjona Ana
Published: January 2017

Conventional wisdom portrays war zones as chaotic and anarchic. In reality, however, they are often orderly. This work introduces a new phenomenon in the study of civil war: wartime social order. It investigates theoretically and empirically the emergence and functioning of social order in conflict zones. By theorizing the interaction between combatants and civilians and how they impact wartime institutions, the study delves into rebel behavior, civilian agency and their impact on the conduct of war. Based on years of fieldwork in Colombia, the theory is tested with qualitative and quantitative evidence on communities, armed groups, and individuals in conflict zones. The study shows how armed groups strive to rule civilians, and how the latter influence the terms of that rule. The theory and empirical results illuminate our understanding of civil war, institutions, local governance, non-violent resistance, and the emergence of political order.
Prudentius, Spain, and Late Antique Christianity
Authors: Hershkowitz Paula
Published: January 2017

This book provides an innovative approach to the Hispano-Roman Christian poet Prudentius and his poetry. It is a breakthrough in Prudentian scholarship which unifies the differing disciplines of history, archaeology, literature and art history in arguing that Prudentius and his envisaged Spanish audience cannot be fully understood in isolation from their environment in late fourth- and early fifth-century Spain. Paula Hershkowitz focuses on Prudentius' Peristephanon, his collection of verses celebrating the deaths of martyrs, and places these poems within the context of Prudentius' world, uniquely employing material, visual and textual remains as evidence for its religious, social and cultural affiliations. It also draws on this material evidence to contextualise Prudentius' awareness of the significance of the visual as a means of promoting beliefs against the background of this crucial formative period in religious history when many of his Spanish audience were not yet fully committed to the Christian faith.
Drag reduction of circular cylinders by porous coating on the leeward side
Authors: Klausmann Katharina , Ruck Bodo
Published: January 2017

The present paper describes the effect of drag reduction of circular cylinders due to a porous coating on their leeward sides. To investigate the coating effect, experiments were conducted in a wind tunnel of Goettingen type. Systematic drag measurements were carried out for different cylinder configurations and flow velocities. The drag measurements were complemented by pressure and particle image velocimetry (PIV) flow field measurements around selected cylinders. The Reynolds numbers were varied in the subcritical range of$3\times 10^{4}<Re<1.4\times 10^{5}$. The results show that a thin porous layer on the leeward side, either incorporated in the cylinder shape or applied on the cylinder surface, leads to an increase of base pressure on the leeward side of the cylinder. It causes a reduction of drag and dampens oscillation amplitudes when compared to a cylinder without coating. Results obtained for different configurations with varying key parameters (coating angles, layer thicknesses and pore sizes of the porous material) clearly indicate the drag-reducing and amplitude-damping potential of leeward coating. The amount of drag reduction and amplitude damping depends on the combination of key parameters. It was demonstrated that the lowered drag coefficients$c_{d}$were almost constant in the tested range of Reynolds numbers. A maximum reduction of drag of 13.2 % was measured. In addition, the results revealed a strong reduction of the pressure fluctuations around cylinders with a leeward coating due to the shift of the vortex region further downstream.
Spatially distributed runoff at the grounding line of a large Greenlandic tidewater glacier inferred from plume modelling
Authors: SLATER DONALD , NIENOW PETER , SOLE ANDREW , COWTON TOM , MOTTRAM RUTH , LANGEN PETER , MAIR DOUGLAS
Published: January 2017

Understanding the drivers of recent change at Greenlandic tidewater glaciers is of great importance if we are to predict how these glaciers will respond to climatic warming. A poorly constrained component of tidewater glacier processes is the near-terminus subglacial hydrology. Here we present a novel method for constraining near-terminus subglacial hydrology with application to marine-terminating Kangiata Nunata Sermia in South-west Greenland. By simulating proglacial plume dynamics using buoyant plume theory and a general circulation model, we assess the critical subglacial discharge, if delivered through a single compact channel, required to generate a plume that reaches the fjord surface. We then compare catchment runoff to a time series of plume visibility acquired from a time-lapse camera. We identify extended periods throughout the 2009 melt season where catchment runoff significantly exceeds the discharge required for a plume to reach the fjord surface, yet we observe no plume. We attribute these observations to spatial spreading of runoff across the grounding line. Persistent distributed drainage near the terminus would lead to more spatially homogeneous submarine melting and may promote more rapid basal sliding during warmer summers, potentially providing a mechanism independent of ocean forcing for increases in atmospheric temperature to drive tidewater glacier acceleration.
The acquisition of tense morphology over time by English second language children with specific language impairment: Testing the cumulative effects hypothesis
Authors: PARADIS JOHANNE , JIA RUITING , ARPPE ANTTI
Published: January 2017

The cumulative effects hypothesis (CEH) claims that bilingual development would be a challenge for children with specific language impairment (SLI). To date, research on second language (L2) children with SLI has been limited mainly to their early years of L2 exposure; however, examining the long-term outcomes of L2 children with SLI is essential for testing the CEH. Accordingly, the present study examined production and grammaticality judgments of English tense morphology from matched groups of L2 children with SLI and L2 children with typical development (TD) for 3 years, from ages 8 to 10 with 4–6 years of exposure to English. This study found that the longitudinal acquisition profile of the L2 children with SLI and TD was similar to the acquisition profile reported for monolinguals with SLI and TD. Furthermore, L2-SLI children's accuracy with tense morphology was similar to that of their monolingual age peers with SLI at the end of the study, and exceeded that of younger monolingual peers with SLI whose age matched the L2 children's length of exposure to English. These findings are not consistent with the CEH, but instead show that morphological acquisition parallel to monolinguals with SLI is possible for L2 children with SLI.
Political support for reforms of the pension system: two experiments
Authors: GOUVEIA ANA FONTOURA
Published: January 2017

We conduct two randomized control trials designed to understand the role of information and priming on the willingness to retrench the pension system. The first entails a survey to a sample of Portuguese voters, who are randomly presented with a text providing factual information about the public pension system. The second surveys a sample of Portuguese University students, randomly presented with an alternative order of questions. We show that more literacy on the pension system has a positive impact on the individual willingness to support reforms. Given that public opinion is usually seen as an important deterrent of effective action by politicians and that the level of voters’ literacy can be influenced by policy action, this analysis may provide useful insights to policy makers faced with the challenge of reforming existent pension systems. Our analysis also suggests that priming effects should not be ignored, given their impact in individuals in the extremes of the political spectrum.
A systematic review of religious beliefs about major end-of-life issues in the five major world religions
Authors: Chakraborty Rajshekhar , El-Jawahri Areej R. , Litzow Mark R. , Syrjala Karen L , Parnes Aric D. , Hashmi Shahrukh K.
Published: January 2017

Objective:

The objective of this study was to examine the religious/spiritual beliefs of followers of the five major world religions about frequently encountered medical situations at the end of life (EoL).

Method:

This was a systematic review of observational studies on the religious aspects of commonly encountered EoL situations. The databases used for retrieving studies were: Ovid MEDLINE In-Process & Other Non-Indexed Citations, Ovid MEDLINE, Ovid EMBASE, Ovid PsycINFO, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, and Scopus. Observational studies, including surveys from healthcare providers or the general population, and case studies were included for review. Articles written from a purely theoretical or philosophical perspective were excluded.

Results:

Our search strategy generated 968 references, 40 of which were included for review, while 5 studies were added from reference lists. Whenever possible, we organized the results into five categories that would be clinically meaningful for palliative care practices at the EoL: advanced directives, euthanasia and physician-assisted suicide, physical requirements (artificial nutrition, hydration, and pain management), autopsy practices, and other EoL religious considerations. A wide degree of heterogeneity was observed within religions, depending on the country of origin, level of education, and degree of intrinsic religiosity.

Significance of results:

Our review describes the religious practices pertaining to major EoL issues and explains the variations in EoL decision making by clinicians and patients based on their religious teachings and beliefs. Prospective studies with validated tools for religiosity should be performed in the future to assess the impact of religion on EoL care.
Psychiatric rehabilitation in Europe
Authors: Rössler W. , Drake R. E.
Published: January 2017

To describe the core elements of modern psychiatric rehabilitation. Based on selected examples we describe the discussion about values in mental health care with focus on Europe. We present outcome data from studies, which have tried to implement care structures based on this value discussion. In the second half of the 20th century, mental health care in all European and other high-income countries changed conceptually and structurally. Deinstitutionalisation reduced the number of psychiatric beds and transferred priority to outpatient care and community-based services, but community mental health programs developed differently across and within these countries. High-income countries in Europe continued to invest in costly traditional services that were neither evidence-based nor person-centered by emphasising inpatient services, sheltered group homes and sheltered workshops. We argue that evidence-based, person-centred, recovery-oriented psychiatric rehabilitation offers a parsimonious solution to developing a consensus plan for community-based care in Europe. The challenges to scaling up effective psychiatric rehabilitation services in high-income countries are not primarily a lack of resources, but rather a lack of political will and inefficient use and dysfunctional allocation of resources.
Efficacy of an Intervention Program to Improve Employability of University Students
Authors: Hernández-Fernaud Estefanía , Ruiz-de la Rosa Carmen Inés , Negrín Fátima , Ramos-Sapena Yeray , Hernández Bernardo
Published: January 2017

In the current socioeconomic situation, the need to improve employability of potential workers is especially relevant. The aim of this study was to evaluate the efficacy of an intervention program focusing on improving employability of university students. To do this, a two-group study was designed: one group undertook the intervention program and the other group were used for comparison. Two measurements were taken at different times (pre-intervention and post-intervention). The sample consisted of 271 university students. The results show that the group that underwent the intervention program improved their perceived employability F(1, 269) = 17.49, p < .001; η2 = .06, openness to learning F(1, 269) = 4.24, p < .05; η2 = .02, self-efficacy for labor market insertion F(1, 269) = 75.70, p < .001; η2 = .22 and for teamwork F(1, 269) = 39.43, p < .001; η2 = .13, and their knowledge of employment resources F(1, 269) = 512.89, p < .001; η2 = .66 compared to the group that did not. Furthermore, there was a high level of satisfaction of participants with the intervention program.
Interactions between C-reactive protein and traditional risk factors in predicting mortality of older adults
Authors: Rudolf Henrik , Wall Naemi , Klaassen-Mielke Renate , Thiem Ulrich , Diehm Curt , Trampisch Hans-Joachim , Krause Dietmar
Published: January 2017

Abstract. Background: Elevated levels of C-reactive protein (CRP) are known to be associated with cardiovascular (CV) morbidity and mortality in older adults, however, there seems to be heterogeneity of this association across subsets of individuals. We aim to assess the effects of interactions between CRP and one of the following traditional CV risk factors regarding all-cause mortality in unselected elderly men and women: age, sex, body mass index, diabetes, and hypertension. Patients and methods: Three hundred and forty-four general practitioners all over Germany enrolled 6,817 unselected participants, aged 65 years or older, and performed thorough examinations, including CRP measurement at baseline (getABI study). All-cause mortality was determined in the following seven years. Cox regression analyses were done using uni- and multivariable models. Results: At baseline 4,172 participants of this cohort had a CRP value of ≤ 3 mg/L (low level CRP group), 2,645 participants had a CRP value of > 3 mg/L (high level CRP group). The unadjusted hazard ratio for all-cause death of the high level CRP group compared to the low level CRP group was 1.49 (95 % confidence interval [95 %CI] 1.34 to 1.66). After adjustment for sex, age, education, peripheral artery disease/media sclerosis, other prior vascular events, smoking status, diabetes, systolic blood pressure, antihypertensive medication, body mass index, cholesterol, and statin use, the hazard ratio was 1.34 (95 %CI 1.20 to 1.50). Significant interactions with CRP were found for sex (adjusted hazard ratio 1.38, 95 %CI 1.11 to 1.72), age (0.75, 95 %CI 0.60 to 0.94), and baseline systolic blood pressure (0.64, 95 % CI 0.51 to 0.81). The interactions of CRP with body mass index and of CRP with diabetes were not significant. Conclusions: In older German adults, there seem to be effect modifications by age, sex, and arterial hypertension regarding the effect of CRP in the prediction of all-cause mortality.
Berberine-sonodynamic therapy induces autophagy and lipid unloading in macrophage
Authors: Kou Jiayuan Y , Li Ying , Zhong Zhaoyu Y , Jiang Yueqing Q , Li Xuesong S , Han Xiaobo B , Liu Zhongni N , Tian Ye , Yang Liming M
Published: January 2017

Impaired autophagy in macrophages accompanies the progression of atherosclerosis and contributes to lipid loading in plaques and ineffective lipid degradation. Therefore, evoking autophagy and its associated cholesterol efflux may provide a therapeutic treatment for atherosclerosis. In the present study, berberine-mediated sonodynamic therapy (BBR-SDT) was used to induce autophagy and cholesterol efflux in THP-1 macrophages and derived foam cells. Following BBR-SDT, autophagy was increased in the macrophages, autophagy resistance in the foam cells was prevented, and cholesterol efflux was induced. The first two effects were blocked by the reactive oxygen species scavenger, N-acetyl cysteine. BBR-SDT also reduced the phosphorylation of Akt and mTOR, two key molecules in the PI3K/AKT/mTOR signaling pathway, which is responsible for inducing autophagy. Correspondingly, treatment with the autophagy inhibitor, 3-methyladenine, or the PI3K inhibitor, LY294002, abolished the autophagy-induced effects of BBR-SDT. Furthermore, induction of cholesterol efflux by BBR-SDT was reversed by an inhibition of autophagy by 3-methyladenine or by a small interfering RNA targeting Atg5. Taken together, these results demonstrate that BBR-SDT effectively promotes cholesterol efflux by increasing reactive oxygen species generation, and this subsequently induces autophagy via the PI3K/AKT/mTOR signaling pathway in both ‘normal’ macrophages and lipid-loaded macrophages (foam cells). Thus, BBR-SDT may be a promising atheroprotective therapy to inhibit the progression of atherosclerosis and should be further studied.
Cellular prion protein mediates early apoptotic proteome alternation and phospho-modification in human neuroblastoma cells
Authors: Zafar Saima , Behrens Christina , Dihazi Hassan , Schmitz Matthias , Zerr Inga , Schulz-Schaeffer Walter J , Ramljak Sanja , Asif Abdul R
Published: January 2017

Anti-apoptotic properties of physiological and elevated levels of the cellular prion protein (PrPc) under stress conditions are well documented. Yet, detrimental effects of elevated PrPc levels under stress conditions, such as exposure to staurosporine (STS) have also been described. In the present study, we focused on discerning early apoptotic STS-induced proteome and phospho-proteome changes in SH-SY5Y human neuroblastoma cells stably transfected either with an empty or PRNP-containing vector, expressing physiological or supraphysiological levels of PrPc, respectively. PrPc-overexpression per se appears to stress the cells under STS-free conditions as indicated by diminished cell viability of PrPc-overexpressing versus control cells. However, PrPc-overexpression becomes advantageous following exposure to STS. Thus, only a short exposure (2 h) to 1 μM STS results in lower survival rates and significantly higher caspase-3 activity in control versus PrPc-overexpressing cells. Hence, by exposing both experimental groups to the same apoptotic conditions we were able to induce apoptosis in control, but not in PrPc-overexpressing cells (as assessed by caspase-3 activity), which allowed for filtering out proteins possibly contributing to protection against STS-induced apoptosis in PrPc-overexpressing cells. Among other proteins regulated by different PrPc levels following exposure to STS, those involved in maintenance of cytoskeleton integrity caught our attention. In particular, the finding that elevated PrPc levels significantly reduce profilin-1 (PFN-1) expression. PFN-1 is known to facilitate STS-induced apoptosis. Silencing of PFN-1 expression by siRNA significantly increased viability of PrPc-overexpressing versus control cells, under STS treatment. In addition, PrPc-overexpressing cells depleted of PFN-1 exhibited increased viability versus PrPc-overexpressing cells with preserved PFN-1 expression, both subjected to STS. Concomitant increase in caspase-3 activity was observed in control versus PrPc-overexpressing cells after treatment with siRNA- PFN-1 and STS. We suggest that reduction of PFN-1 expression by elevated levels of PrPc may contribute to protective effects PrPc-overexpressing SH-SY5Y cells confer against STS-induced apoptosis.
Foot-and-mouth disease virus infection suppresses autophagy and NF-кB antiviral responses via degradation of ATG5-ATG12 by 3Cpro
Authors: Fan Xuxu , Han Shichong , Yan Dan , Gao Yuan , Wei Yanquan , Liu Xiangtao , Liao Ying , Guo Huichen , Sun Shiqi
Published: January 2017

Autophagy-related protein ATG5-ATG12 is an essential complex for the autophagophore elongation in autophagy, which has been reported to be involved in foot-and-mouth disease virus (FMDV) replication. Previous reports show that ATG5-ATG12 positively or negatively regulates type I interferon (IFN-α/β) pathway during virus infection. In this study, we found that FMDV infection rapidly induced LC3 lipidation and GFP-LC3 subcellular redistribution at the early infection stage in PK-15 cells. Along with infection time course to 2–5 h.p.i., the levels of LC3II and ATG5-ATG12 were gradually reduced. Further study showed that ATG5-ATG12 was degraded by viral protein 3Cpro, demonstrating that FMDV suppresses autophagy along with viral protein production. Depletion of ATG5-ATG12 by siRNA knock down significantly increased the FMDV yields, whereas overexpression of ATG5-ATG12 had the opposite effects, suggesting that degradation of ATG5-ATG12 benefits virus growth. Further experiment showed that overexpression of ATG5-ATG12 positively regulated NF-кB pathway during FMDV infection, marked with promotion of IKKα/β phosphorylation and IκBα degradation, inhibition of p65 degradation, and facilitation of p65 nuclear translocation. Meanwhile, ATG5-ATG12 also promoted the phosphorylation of TBK1 and activation of IRF3 via preventing TRAF3 degradation. The positive regulation of NF-кB and IRF3 pathway by ATG5-ATG12 resulted in enhanced expression of IFN-β, chemokines/cytokines, and IFN stimulated genes, including anti-viral protein PKR. Altogether, above findings suggest that ATG5-ATG12 positively regulate anti-viral NF-κB and IRF3 signaling during FMDV infection, thereby limiting FMDV proliferation. FMDV has evolved mechanisms to counteract the antiviral function of ATG5-ATG12, via degradation of them by viral protein 3Cpro.
IL-17-mediated mitochondrial dysfunction impairs apoptosis in rheumatoid arthritis synovial fibroblasts through activation of autophagy
Authors: Kim Eun Kyung , Kwon Jeong-Eun , Lee Seon-Young , Lee Eun-Jung , Kim Da Som , Moon Su-Jin , Lee Jennifer , Kwok Seung-Ki , Park Sung-Hwan , Cho Mi-La
Published: January 2017

Fibroblast-like synoviocytes (FLSs) are a major cell population of the pannus that invades cartilage and bone in rheumatoid arthritis (RA). FLS resistance to apoptosis is a major characteristic of RA. The aims of this study were to investigate the effects of interleukin-17 (IL-17) and IL-17-producing T helper (Th17) cells on resistance to apoptosis in FLSs from RA patients (RA FLSs) and their roles in mitochondrial dysfunction and autophagy. Mitochondrial function was assessed in RA FLSs and FLSs from osteoarthritis patients (OA FLSs). FLSs were treated with IL-17 and their morphological features, respiratory level and mitochondrial gene expression were measured. The effects of IL-17 and Th17 cells on the relationship between autophagy and apoptosis were evaluated by measuring the expression of apoptosis-related genes using sodium nitroprusside or 3-methyladenine. The mitochondria of FLSs isolated from RA and osteoarthritis patients displayed different morphological and physiological features. RA FLSs exhibited greater autophagosome formation and greater dysfunction of mitochondrial respiration compared with OA FLSs. IL-17 induced mitochondrial dysfunction and autophagosome formation in RA FLSs, suggesting that they were resistant to apoptosis. Autophagy-related antiapoptosis induced by IL-17 was restored by inhibition of autophagy, suggesting a relationship between mitochondrial dysfunction and cell survival in RA FLSs. Th17 cells and IL-17 increased autophagy of RA FLSs by causing mitochondrial dysfunction. Our findings suggest that, in RA, interactions between RA FLSs and Th17 cells may be involved in the tumorous growth of FLSs and the formation of pannus in joints.
Tumour-derived Interleukin 35 promotes pancreatic ductal adenocarcinoma cell extravasation and metastasis by inducing ICAM1 expression
Authors: Huang Chongbiao , Li Na , Li Zengxun , Chang Antao , Chen Yanan , Zhao Tiansuo , Li Yang , Wang Xiuchao , Zhang Wei , Wang Zhimin , Luo Lin , Shi Jingjing , Yang Shengyu , Ren He , Hao Jihui
Published: January 2017

Interleukin 35 (IL-35) is a novel member of the IL-12 family, consisting of an EBV-induced gene 3 (EBI3) subunit and a P35 subunit. IL-35 is an immune-suppressive cytokine mainly produced by regulatory T cells. However, the role of IL-35 in cancer metastasis and progression is not well understood. Here we demonstrate that IL-35 is overexpressed in human pancreatic ductal adenocarcinoma (PDAC) tissues, and that IL-35 overexpression is associated with poor prognosis in PDAC patients. IL-35 has critical roles in PDAC cell extravasation and metastasis by facilitating the adhesion to endothelial cells and transendothelial extravasation. Mechanistically, IL-35 promotesICAM1overexpression through a GP130-STAT1 signalling pathway, which facilitates endothelial adhesion and transendothelial migration via an ICAM1–fibrinogen–ICAM1 bridge. In an orthotopic xenograft model, IL-35 promotes spontaneous pancreatic cancer metastasis in anICAM1-dependent manner. Together, our results indicate additional functions of IL-35 in promoting PDAC metastasis through mediatingICAM1expression.
Shape-dependent ordering of gold nanocrystals into large-scale superlattices
Authors: Gong Jianxiao , Newman Richmond S. , Engel Michael , Zhao Man , Bian Fenggang , Glotzer Sharon C. , Tang Zhiyong
Published: January 2017

Self-assembly of individual building blocks into highly ordered structures, analogous to spontaneous growth of crystals from atoms, is a promising approach to realize the collective properties of nanocrystals. Yet the ability to reliably produce macroscopic assemblies is unavailable and key factors determining assembly quality/yield are not understood. Here we report the formation of highly ordered superlattice films, with single crystalline domains of up to half a millimetre in two dimensions and thickness of up to several microns from nanocrystals with tens of nanometres in diameter. Combining experimental and computational results for gold nanocrystals in the shapes of spheres, cubes, octahedra and rhombic dodecahedra, we investigate the entire self-assembly process from disordered suspensions to large-scale ordered superlattices induced by nanocrystal sedimentation and eventual solvent evaporation. Our findings reveal that the ultimate coherence length of superlattices strongly depends on nanocrystal shape. Factors inhibiting the formation of high-quality large-scale superlattices are explored in detail.
The impact of microRNAs on transcriptional heterogeneity and gene co-expression across single embryonic stem cells
Authors: Gambardella Gennaro , Carissimo Annamaria , Chen Amy , Cutillo Luisa , Nowakowski Tomasz J. , di Bernardo Diego , Blelloch Robert
Published: January 2017

MicroRNAs act posttranscriptionally to suppress multiple target genes within a cell population. To what extent this multi-target suppression occurs in individual cells and how it impacts transcriptional heterogeneity and gene co-expression remains unknown. Here we used single-cell sequencing combined with introduction of individual microRNAs. miR-294 and let-7c were introduced into otherwise microRNA-deficient Dgcr8 knockout mouse embryonic stem cells. Both microRNAs induce suppression and correlated expression of their respective gene targets. The two microRNAs had opposing effects on transcriptional heterogeneity within the cell population, with let-7c increasing and miR-294 decreasing the heterogeneity between cells. Furthermore, let-7c promotes, whereas miR-294 suppresses, the phasing of cell cycle genes. These results show at the individual cell level how a microRNA simultaneously has impacts on its many targets and how that in turn can influence a population of cells. The findings have important implications in the understanding of how microRNAs influence the co-expression of genes and pathways, and thus ultimately cell fate.
The prevalence of CTNNB1 mutations in primary aldosteronism and consequences for clinical outcomes
Authors: Wu Vin-Cent , Wang Shuo-Meng , Chueh Shih-Chieh Jeff , Yang Shao-Yu , Huang Kuo-How , Lin Yen-Hung , Wang Jian-Jhong , Connolly Rory , Hu Ya-Hui , Gomez-Sanchez Celso E. , Peng Kang-Yung , Wu Kwan-Dun
Published: January 2017

Constitutive activation of the Wnt pathway/β-catenin signaling may be important in aldosterone-producing adenoma (APA). However, significant gaps remain in our understanding of the prevalence and clinical outcomes after adrenalectomy in APA patients harboringCTNNB1mutations. The molecular expression of CYP11B2 and gonadal receptors in adenomas were also explored. Adenomas from 219 APA patients (95 men; 44.2%; aged 50.5 ± 11.9 years) showed a high rate of somatic mutations (n = 128, 58.4%). The majority of them harboredKCNJ5mutations (n = 116, 52.9%); 8 patients (3.7%, 6 women) hadCTNNB1mutations. Patients with APAs harboringCTNNB1mutations were older and had shorter duration of hypertension. After adrenalectomy,CTNNB1mutation carriers had a higher possibility (87.5%) of residual hypertension than other APA patients. APAs harboringCTNNB1mutations have heterogeneous staining of β-catenin and variable expression of gonadal receptors and both CYP11B1 and CYP11B2. This suggests thatCTNNB1mutations may be more related to tumorigenesis rather than excessive aldosterone production.
WHSC1L1-mediated EGFR mono-methylation enhances the cytoplasmic and nuclear oncogenic activity of EGFR in head and neck cancer
Authors: Saloura Vassiliki , Vougiouklakis Theodore , Zewde Makda , Deng Xiaolan , Kiyotani Kazuma , Park Jae-Hyun , Matsuo Yo , Lingen Mark , Suzuki Takehiro , Dohmae Naoshi , Hamamoto Ryuji , Nakamura Yusuke
Published: January 2017

While multiple post-translational modifications have been reported to regulate the function of epidermal growth factor receptor (EGFR), the effect of protein methylation on its function has not been well characterized. In this study, we show that WHSC1L1 mono-methylates lysine 721 in the tyrosine kinase domain of EGFR, and that this methylation leads to enhanced activation of its downstream ERK cascade without EGF stimulation. We also show that EGFR K721 mono-methylation not only affects the function of cytoplasmic EGFR, but also that of nuclear EGFR. WHSC1L1-mediated methylation of EGFR in the nucleus enhanced its interaction with PCNA in squamous cell carcinoma of the head and neck (SCCHN) cells and resulted in enhanced DNA synthesis and cell cycle progression. Overall, our study demonstrates the multifaceted oncogenic function of the protein lysine methyltransferase WHSC1L1 in SCCHN, which is mediated through direct non-histone methylation of the EGFR protein with effects both in its cytoplasmic and nuclear functions.