bluuebunny/crossref_metadata_2025 huggingface dataset:
Coil‐helix and sheet‐helix block copolymers via macroinitiation from telechelic ROMP polymers
Authors: Elacqua Elizabeth , Croom Anna , Lye Diane S. , Weck Marcus
Published: April 2017

Coil‐helix and sheet‐helix block copolymers are synthesized by combining the ring‐opening metathesis polymerization (ROMP) of norbornene or paracyclophanediene with the anionic polymerization of phenyl isocyanide. Key to the design is the use of an μ‐ethynyl palladium (II) functionalized chain‐transfer agent (CTA) that can be exploited in a stepwise manner for the termination of ROMP and the initiation of the anionic polymerization. Both the coil‐ and sheet‐macroinitiators, and the ensuing covalent block copolymers, are analyzed using 1H NMR spectroscopy and gel‐permeation chromatography. In all cases, the Pd‐end group is maintained and all polymers demonstrate a monomodal distribution with dispersities (Đ) of 1.1–1.4. The resulting helix‐coil and helix‐sheet block copolymers formed by the macroinitiation route still demonstrate their intrinsic properties (fluorescence, preferential helix‐sense). © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017, 55, 2991–2998
Grubbs‐inspired metathesis in the Moore group
Authors: Moneypenny Timothy P. , Liu Huiying , Yang Anna , Robertson Ian D. , Moore Jeffrey S.
Published: April 2017

Alkene metathesis has proven to be a powerful method for carboncarbon bond formation, particularly in the field of polymer and materials science. The availability of various tailor‐made catalysts not only enables the synthesis of well‐defined polymers but facilitates the development of functional, stimuli–responsive materials. This highlight, dedicated to Professor Robert Grubbs on his 75th birthday, focuses on the various research efforts in our group utilizing both alkene and alkyne metatheses and the interesting materials derived from them. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017, 55, 2935–2948
Dynamic safety risk modeling of process systems using bayesian network
Authors: Zarei Esmaeil , Azadeh Ali , Aliabadi Mostafa Mirzaei , Mohammadfam Iraj
Published: April 2017

Process complex systems in particular oil and gas plants due to dealing with hazardous materials at severe process conditions are much prone to catastrophic accidents. In this context, safety risk analysis is a crucial tool to develop effective strategies to prevent accident and provide mitigative measures. Dynamic risk analysis (DRA) is one of the most practical approaches for risk analysis that helps provide safer operations of complex process systems. The present work is aimed at demonstrating the application of an integrated DRA approach to comprehensive quantitative modeling and analysis of the both aspects of risk, that is, probability and consequence assessments. In this approach, first, the worst case scenario is identified and then a robust tool is developed for dynamic accident scenario modeling and risk assessment by means of Bayesian Network. This approach is applied to risk analysis of a flammable liquid storage system at a gas refinery. The work provides valuable information on the identification and comprehensive analysis of worst case accident scenarios, their main consequences, critical basic events, and minimal cut sets which lead to accident scenarios and also for dynamic updating of probabilities and risk. The obtained results are more appropriate and rigorous to developing preventive and mitigative strategies for potential accident scenarios and thus increase the safety level in the complex process systems. © 2017 American Institute of Chemical Engineers Process Saf Prog 36: 399–407, 2017
Co‐sensitization by triarylamine dyes for improved dye‐sensitized solar cells
Authors: Xie Yan , Wu Liang , Han Liang , Gao Jianrong
Published: April 2017

To improve the performance of solar cells, two previous triarylamine dyes with different planarities reported by us, AFL2 and AFL3, were combined with dye D1 as a cosensitizer and tested for the co‐sensitization of dye‐sensitized solar cells (DSSCs) without using Al2O3‐coated TiO2. The photophysical and photovoltaic performance as well as the electrochemical properties of the co‐sensitized DSSCs were investigated. The results suggested an enhancement of the efficiency, which was in accordance with the increase in molar ratio of AFL2 and the decrease of AFL3. Other data revealed that lower molar ratios of AFL2/D1 did not only compensate for the peak‐valley of IPCE near 400 nm but also delayed charge recombination, and that AFL3/D1 at lower molar ratios could lead to dye aggregation. The photovoltaic efficiencies of the resulting AFL2 and AFL3 increased from 4.83% and 5.81–5.87% (ratio of 1:1) and 6.44% (ratio of 4:1), corresponding to 20 and 11% improvement, respectively.
Recent Advances in Atomic Metal Doping of Carbon‐based Nanomaterials for Energy Conversion
Authors: Bayatsarmadi Bita , Zheng Yao , Vasileff Anthony , Qiao Shi‐Zhang
Published: April 2017

Nanostructured metal‐contained catalysts are one of the most widely used types of catalysts applied to facilitate some of sluggish electrochemical reactions. However, the high activity of these catalysts cannot be sustained over a variety of pH ranges. In an effort to develop highly active and stable metal‐contained catalysts, various approaches have been pursued with an emphasis on metal particle size reduction and doping on carbon‐based supports. These techniques enhances the metal‐support interactions, originating from the chemical bonding effect between the metal dopants and carbon support and the associated interface, as well as the charge transfer between the atomic metal species and carbon framework. This provides an opportunity to tune the well‐defined metal active centers and optimize their activity, selectivity and stability of this type of (electro)catalyst. Herein, recent advances in synthesis strategies, characterization and catalytic performance of single atom metal dopants on carbon‐based nanomaterials are highlighted with attempts to understand the electronic structure and spatial arrangement of individual atoms as well as their interaction with the supports. Applications of these new materials in a wide range of potential electrocatalytic processes in renewable energy conversion systems are also discussed with emphasis on future directions in this active field of research.
RETRACTED ARTICLE: The effect of gamma-enhancing binaural beats on the control of feature bindings
Authors: Colzato Lorenza S. , Steenbergen Laura , Sellaro Roberta
Published: April 2017

Binaural beats represent the auditory experience of an oscillating sound that occurs when two sounds with neighboring frequencies are presented to one’s left and right ear separately. Binaural beats have been shown to impact information processing via their putative role in increasing neural synchronization. Recent studies of feature-repetition effects demonstrated interactions between perceptual features and action-related features: repeating only some, but not all features of a perception–action episode hinders performance. These partial-repetition (or binding) costs point to the existence of temporary episodic bindings (event files) that are automatically retrieved by repeating at least one of their features. Given that neural synchronization in the gamma band has been associated with visual feature bindings, we investigated whether the impact of binaural beats extends to the top-down control of feature bindings. Healthy adults listened to gamma-frequency (40 Hz) binaural beats or to a constant tone of 340 Hz (control condition) for ten minutes before and during a feature-repetition task. While the size of visuomotor binding costs (indicating the binding of visual and action features) was unaffected by the binaural beats, the size of visual feature binding costs (which refer to the binding between the two visual features) was considerably smaller during gamma-frequency binaural beats exposure than during the control condition. Our results suggest that binaural beats enhance selectivity in updating episodic memory traces and further strengthen the hypothesis that neural activity in the gamma band is critically associated with the control of feature binding.
A Prospective, Holistic, Multicenter Approach to Tracking and Understanding Bloodstream Infections in Pediatric Hematology-Oncology Patients
Authors: Gaur Aditya H. , Bundy David G. , Werner Eric J. , Hord Jeffrey D. , Miller Marlene R. , Tang Li , Lawlor John P. , Billett Amy L. ,   Children’s Hospital Association Childhood Cancer and Blood Disorders Network (CCBDN)
Published: April 2017

OBJECTIVE

To assess the burden of bloodstream infections (BSIs) among pediatric hematology-oncology (PHO) inpatients, to propose a comprehensive, all-BSI tracking approach, and to discuss how such an approach helps better inform within-center and across-center differences in CLABSI rate

DESIGN

Prospective cohort study

SETTING

US multicenter, quality-improvement, BSI prevention network

PARTICIPANTS

PHO centers across the United States who agreed to follow a standardized central-line–maintenance care bundle and track all BSI events and central-line days every month.

METHODS

Infections were categorized as CLABSI (stratified by mucosal barrier injury–related, laboratory-confirmed BSI [MBI-LCBI] versus non–MBI-LCBI) and secondary BSI, using National Healthcare Safety Network (NHSN) definitions. Single positive blood cultures (SPBCs) with NHSN defined common commensals were also tracked.

RESULTS

Between 2013 and 2015, 34 PHO centers reported 1,110 BSIs. Among them, 708 (63.8%) were CLABSIs, 170 (15.3%) were secondary BSIs, and 232 (20.9%) were SPBCs. Most SPBCs (75%) occurred in patients with profound neutropenia; 22% of SPBCs were viridans group streptococci. Among the CLABSIs, 51% were MBI-LCBI. Excluding SPBCs, CLABSI rates were higher (88% vs 77%) and secondary BSI rates were lower (12% vs 23%) after the NHSN updated the definition of secondary BSI (P<.001). Preliminary analyses showed across-center differences in CLABSI versus secondary BSI and between SPBC and CLABSI versus non-CLABSI rates.

CONCLUSIONS

Tracking all BSIs, not just CLABSIs in PHO patients, is a patient-centered, clinically relevant approach that could help better assess across-center and within-center differences in infection rates, including CLABSI. This approach enables informed decision making by healthcare providers, payors, and the public.

Infect Control Hosp Epidemiol 2017;38:690–696
Prospective association between tobacco smoking and death by suicide: a competing risks hazard analysis in a large twin cohort with 35-year follow-up
Authors: Evins A. E. , Korhonen T. , Kinnunen T. H. , Kaprio J.
Published: April 2017

Background

The relationship between smoking and suicide remains controversial.

Method

A total of 16 282 twin pairs born before 1958 in Finland and alive in 1974 were queried with detailed health and smoking questionnaires in 1975 and 1981, with response rates of 89% and 84%. Smoking status and dose, marital, employment, and socio-economic status, and indicators of psychiatric and somatic illness were assessed at both time points. Emergent psychiatric and medical illness and vital status, including suicide determined by forensic autopsy, were evaluated over 35-year follow-up through government registries. The association between smoking and suicide was determined in competing risks hazard models. In twin pairs discordant for smoking and suicide, the prospective association between smoking and suicide was determined using a matched case–control design.

Results

Smokers had a higher cumulative suicide incidence than former or never smokers. Heavy smokers had significantly higher suicide risk [hazard ratio (HR) 3.47, 95% confidence interval (CI) 2.31–5.22] than light smokers (HR 2.30, 95% CI 1.61–3.23) (p = 0.017). Compared with never smokers, smokers, but not former smokers, had increased suicide risk (HR 2.56, 95% CI 1.43–4.59), adjusting for depressive symptoms, alcohol and sedative–hypnotic use, and excluding those who developed serious somatic or psychiatric illness. In twin pairs discordant for smoking and suicide, suicide was more likely in smokers [odds ratio (OR) 6.0, 95% CI 2.06–23.8].

Conclusions

Adults who smoked tobacco were more likely to die by suicide, with a large, dose-dependent effect. This effect remained after consideration of many known predictors of suicide and shared familial effects, consistent with the hypothesis that exposure to tobacco smoke increases the risk of suicide.
PROSPER delivery of universal preventive interventions with young adolescents: long-term effects on emerging adult substance misuse and associated risk behaviors
Authors: Spoth R. , Redmond C. , Shin C. , Greenberg M. T. , Feinberg M. E. , Trudeau L.
Published: April 2017

Background

Substance misuse and associated health-risking behaviors are prevalent in emerging adulthood. There is a knowledge gap concerning the post-high school effects of community-based delivery systems for universal preventive interventions implemented during young adolescence. This study reports effects of the PROSPER delivery system through age 19, 7.5 years past baseline.

Methods

A cohort sequential design included 28 public school districts randomly assigned to the PROSPER partnership delivery system or usual-programming conditions. PROSPER community teams implemented a family-focused intervention in 6th grade and a school-based intervention in 7th grade. Outcomes for the age 19, post-high school report included lifetime, current, and frequency of substance misuse, as well as antisocial and health-risking sexual behaviors. Intent-to-treat, multi-level analyses of covariance of point-in-time outcomes were conducted, along with analyses of risk-related moderation of intervention effects.

Results

Results showed emerging adults from PROSPER communities reported significantly lower substance misuse across a range of types of substances, with relative reduction rates of up to 41.0%. No significant findings were observed for associated antisocial and health-risking sexual behavior indices; or for lifetime rates of sexually transmitted infections. Risk-related moderation effects were non-significant, suggesting generally comparable outcomes across higher- and lower-risk subgroups of emerging adults.

Conclusions

The PROSPER delivery system for brief universal preventive interventions has potential for public health impact by reducing long-term substance misuse, with positive results extending beyond high school.
Herder on the Emancipatory Power of Religion and Religious Education
Authors: Czobor-Lupp Mihaela
Published: April 2017

Johann Gottfried Herder was both a philosopher and an active Lutheran minister, who constantly faced the difficult task of negotiating in his own work and life, in his public speeches and activities, the relationship to be established between reason and religion, both their limits and the promises they carry for each other. This article examines Herder's writings on language and reason, religion, myth, and history with the intention of putting together an account of religion and reason along lines that emphasize their continuity with each other. I argue that, in Herder's view, religion and religious education can play an active role in forming the disposition of individuals to humanity, in cultivating both their freedom and their capacity to empathize with others and love them, thus helping to materialize the emancipatory project of the Enlightenment.
‘An Old Man Emanating Kindness’: Dario Fo at ISTA, 1996
Authors: Tyszka Juliusz
Published: April 2017

In 1996 the Polish theatre scholar Juliusz Tyszka was present at the gathering of the International School of Theatre Anthropology (ISTA) in Copenhagen. Here, Dario Fo – in company with his wife and theatrical partner Franca Rame, also a contributor – was among the few invited to participate in both sessions of the conference: ‘Performers’ Bios: Whispering Winds of Theatre and Dance’ and ‘Theatre in a Multicultural Society’. Though already seventy years old and still in recovery from a recent stroke, Fo was incapable of confining himself to a conventional lecture, but (against his doctor's advice) combined his talk with performing the points he was making, whether imitating the curves of a voluptuous girl or enacting a speech in his universal ‘language’ of ‘gramelot’. He was to live on for another twenty years before his death at the age of ninety on 13 October 2016, outliving Franca Rame by just three years. Juliusz Tyszka, an advisory editor of NTQ and a regular contributor to the journal, is head of the Unit of Performance Studies, Institute of Cultural Studies, Adam Mickiewicz University at Poznań, Poland.
Testing the limits: Extending attachment-based intervention effects to infant cognitive outcome and parental stress
Authors: Dubois-Comtois Karine , Cyr Chantal , Tarabulsy George M. , St-Laurent Diane , Bernier Annie , Moss Ellen
Published: April 2017

Using a sample of 41 infants and toddlers (21 interventions, 20 controls) who were neglected or at serious risk for neglect, this randomized clinical trial examined the efficacy of a parent–child attachment-based video-feedback intervention on parental sensitivity, parental stress, and child mental/psychomotor development. Results showed that following the 8-week intervention, scores for maternal sensitivity and child mental and psychomotor development were higher in the intervention group than in the control group. The intervention appears to have no effect on self-reports of stress. All parents report lower levels of stress postintervention; however, when defensive responding is not considered (i.e., extremely low score of parental stress), parents in the control group report somewhat lower scores, raising questions as to the significance of this finding. Considering the small nature of our sample, replication of the present results is needed. Nevertheless, the present findings contribute to the burgeoning literature suggesting that the early attachment relationship provides an important context that influences developmental outcome in different spheres and raises questions as to how such intervention strategies may or may not affect the subjective experience of parenting.
Developmental cascade effects of interpersonal psychotherapy for depressed mothers: Longitudinal associations with toddler attachment, temperament, and maternal parenting efficacy
Authors: Handley Elizabeth D. , Michl-Petzing Louisa C. , Rogosch Fred A. , Cicchetti Dante , Toth Sheree L.
Published: April 2017

Using a developmental cascades framework, the current study investigated whether treating maternal depression via interpersonal psychotherapy (IPT) may lead to more widespread positive adaptation for offspring and mothers including benefits to toddler attachment and temperament, and maternal parenting self-efficacy. The participants (N= 125 mother–child dyads; mean mother age at baseline = 25.43 years; 54.4% of mothers were African American; mean offspring age at baseline = 13.23 months) were from a randomized controlled trial of IPT for a sample of racially and ethnically diverse, socioeconomically disadvantaged mothers of infants. Mothers were randomized to IPT (n= 97) or an enhanced community standard control group (n= 28). The results of complier average causal effect modeling showed that engagement with IPT led to significant decreases in maternal depressive symptoms at posttreatment. Moreover, reductions in maternal depression posttreatment were associated with less toddler disorganized attachment characteristics, more adaptive maternal perceptions of toddler temperament, and improved maternal parenting efficacy 8 months following the completion of treatment. Our findings contribute to the emerging literature documenting the potential benefits to children of successfully treating maternal depression. Alleviating maternal depression appears to initiate a cascade of positive adaptation among both mothers and offspring, which may alter the well-documented risk trajectory for offspring of depressed mothers.
Mushrooms Could Provide a Record of Grassland History
Authors: Branscombe Alexandra
Published: April 2017

Scientists measured carbon isotopes in certain types of fungi to assess whether the organisms can track how climate change is affecting grasses.
Multiscale structural and electronic control of molybdenum disulfide foam for highly efficient hydrogen production
Authors: Deng Jiao , Li Haobo , Wang Suheng , Ding Ding , Chen Mingshu , Liu Chuan , Tian Zhongqun , Novoselov K. S. , Ma Chao , Deng Dehui , Bao Xinhe
Published: April 2017

Hydrogen production through water splitting has been considered as a green, pure and high-efficient technique. As an important half-reaction involved, hydrogen evolution reaction is a complex electrochemical process involving liquid-solid-gas three-phase interface behaviour. Therefore, new concepts and strategies of material design are needed to smooth each pivotal step. Here we report a multiscale structural and electronic control of molybdenum disulfide foam to synergistically promote the hydrogen evolution process. The optimized three-dimensional molybdenum disulfide foam with uniform mesopores, vertically aligned two-dimensional layers and cobalt atoms doping demonstrated a high hydrogen evolution activity and stability. In addition, density functional theory calculations indicate that molybdenum disulfide with moderate cobalt doping content possesses the optimal activity. This study demonstrates the validity of multiscale control in molybdenum disulfide via overall consideration of the mass transport, and the accessibility, quantity and capability of active sites towards electrocatalytic hydrogen evolution, which may also be extended to other energy-related processes.
Cognate antigen engagement on parenchymal cells stimulates CD8+ T cell proliferation in situ
Authors: Sutherland Robyn M. , Londrigan Sarah L. , Brady Jamie L. , Carrington Emma M. , Marchingo Julia M. , Heinzel Susanne , Hodgkin Philip D. , Graham Kate L. , Kay Thomas W. , Zhan Yifan , Lew Andrew M.
Published: April 2017

T-cell responses are initiated upon cognate presentation by professional antigen presenting cells in lymphoid tissue. T cells then migrate to inflamed tissues, but further T-cell stimulation in these parenchymal target sites is not well understood. Here we show that T-cell expansion within inflamed tissues is a distinct phase that is neither a classical primary nor classical secondary response. This response, which we term ‘the mezzanine response’, commences within days after initial antigen encounter, unlike the secondary response that usually occurs weeks after priming. A further distinction of this response is that T-cell proliferation is driven by parenchymal cell antigen presentation, without requiring professional antigen presenting cells, but with increased dependence on IL-2. The mezzanine response might, therefore, be a new target for inhibiting T-cell responses in allograft rejection and autoimmunity or for enhancing T-cell responses in the context of microbial or tumour immunity.
Classical synchronization indicates persistent entanglement in isolated quantum systems
Authors: Witthaut Dirk , Wimberger Sandro , Burioni Raffaella , Timme Marc
Published: April 2017

Synchronization and entanglement constitute fundamental collective phenomena in multi-unit classical and quantum systems, respectively, both equally implying coordinated system states. Here, we present a direct link for a class of isolated quantum many-body systems, demonstrating that synchronization emerges as an intrinsic system feature. Intriguingly, quantum coherence and entanglement arise persistently through the same transition as synchronization. This direct link between classical and quantum cooperative phenomena may further our understanding of strongly correlated quantum systems and can be readily observed in state-of-the-art experiments, for example, with ultracold atoms.
Electrically driven cation exchange for in situ fabrication of individual nanostructures
Authors: Zhang Qiubo , Yin Kuibo , Dong Hui , Zhou Yilong , Tan Xiaodong , Yu Kaihao , Hu Xiaohui , Xu Tao , Zhu Chao , Xia Weiwei , Xu Feng , Zheng Haimei , Sun Litao
Published: April 2017

Cation exchange (CE) has been recognized as a particularly powerful tool for the synthesis of heterogeneous nanocrystals. At present, CE can be divided into two categories, namely ion solvation-driven CE reaction and thermally activated CE reaction. Here we report an electrically driven CE reaction to prepare individual nanostructures inside a transmission electron microscope. During the process, Cd is eliminated due to Ohmic heating, whereas Cu+ migrates into the crystal driven by the electrical field force. Contrast experiments reveal that the feasibility of electrically driven CE is determined by the structural similarity of the sulfur sublattices between the initial and final phases, and the standard electrode potentials of the active electrodes. Our experimental results demonstrate a strategy for the selective growth of individual nanocrystals and provide crucial insights into understanding of the microscopic pathways leading to the formation of heterogeneous structures.
Regio- and conformational isomerization critical to design of efficient thermally-activated delayed fluorescence emitters
Authors: Etherington Marc K. , Franchello Flavio , Gibson Jamie , Northey Thomas , Santos Jose , Ward Jonathan S. , Higginbotham Heather F. , Data Przemyslaw , Kurowska Aleksandra , Dos Santos Paloma Lays , Graves David R. , Batsanov Andrei S. , Dias Fernando B. , Bryce Martin R. , Penfold Thomas J. , Monkman Andrew P.
Published: April 2017

Regio- and conformational isomerization are fundamental in chemistry, with profound effects upon physical properties, however their role in excited state properties is less developed. Here two regioisomers of bis(10H-phenothiazin-10-yl)dibenzo[b,d]thiophene-S,S-dioxide, a donor–acceptor–donor (D–A–D) thermally-activated delayed fluorescence (TADF) emitter, are studied. 2,8-bis(10H-phenothiazin-10-yl)dibenzo[b,d]thiophene-S,S-dioxide exhibits only one quasi-equatorial conformer on both donor sites, with charge-transfer (CT) emission close to the local triplet state leading to efficient TADF via spin-vibronic coupling. However, 3,7-bis(10H-phenothiazin-10-yl)dibenzo[b,d]thiophene-S,S-dioxide displays both a quasi-equatorial CT state and a higher-energy quasi-axial CT state. No TADF is observed in the quasi-axial CT emission. These two CT states link directly to the two folded conformers of phenothiazine. The presence of the low-lying local triplet state of the axial conformer also means that this quasi-axial CT is an effective loss pathway both photophysically and in devices. Importantly, donors or acceptors with more than one conformer have negative repercussions for TADF in organic light-emitting diodes.
Simultaneous loss of interlayer coherence and long-range magnetism in quasi-two-dimensional PdCrO2
Authors: Ghannadzadeh S. , Licciardello S. , Arsenijević S. , Robinson P. , Takatsu H. , Katsnelson M. I. , Hussey N. E.
Published: April 2017

In many layered metals, coherent propagation of electronic excitations is often confined to the highly conducting planes. While strong electron correlations and/or proximity to an ordered phase are believed to be the drivers of this electron confinement, it is still not known what triggers the loss of interlayer coherence in a number of layered systems with strong magnetic fluctuations, such as cuprates. Here, we show that a definitive signature of interlayer coherence in the metallic-layered triangular antiferromagnet PdCrO2 vanishes at the Néel transition temperature. Comparison with the relevant energy scales and with the isostructural non-magnetic PdCoO2 reveals that the interlayer incoherence is driven by the growth of short-range magnetic fluctuations. This establishes a connection between long-range order and interlayer coherence in PdCrO2 and suggests that in many other low-dimensional conductors, incoherent interlayer transport also arises from the strong interaction between the (tunnelling) electrons and fluctuations of some underlying order.
Local inhibition of microtubule dynamics by dynein is required for neuronal cargo distribution
Authors: Yogev Shaul , Maeder Celine I. , Cooper Roshni , Horowitz Mark , Hendricks Adam G. , Shen Kang
Published: April 2017

Abnormal axonal transport is associated with neuronal disease. We identified a role for DHC-1, the C. elegans dynein heavy chain, in maintaining neuronal cargo distribution. Surprisingly, this does not involve dynein’s role as a retrograde motor in cargo transport, hinging instead on its ability to inhibit microtubule (MT) dynamics. Neuronal MTs are highly static, yet the mechanisms and functional significance of this property are not well understood. In disease-mimicking dhc-1 alleles, excessive MT growth and collapse occur at the dendrite tip, resulting in the formation of aberrant MT loops. These unstable MTs act as cargo traps, leading to ectopic accumulations of cargo and reduced availability of cargo at normal locations. Our data suggest that an anchored dynein pool interacts with plus-end-out MTs to stabilize MTs and allow efficient retrograde transport. These results identify functional significance for neuronal MT stability and suggest a mechanism for cellular dysfunction in dynein-linked disease.
Chiral acidic amino acids induce chiral hierarchical structure in calcium carbonate
Authors: Jiang Wenge , Pacella Michael S. , Athanasiadou Dimitra , Nelea Valentin , Vali Hojatollah , Hazen Robert M. , Gray Jeffrey J. , McKee Marc D.
Published: April 2017

Chirality is ubiquitous in biology, including in biomineralization, where it is found in many hardened structures of invertebrate marine and terrestrial organisms (for example, spiralling gastropod shells). Here we show that chiral, hierarchically organized architectures for calcium carbonate (vaterite) can be controlled simply by adding chiral acidic amino acids (Asp and Glu). Chiral, vaterite toroidal suprastructure having a ‘right-handed’ (counterclockwise) spiralling morphology is induced by L-enantiomers of Asp and Glu, whereas ‘left-handed’ (clockwise) morphology is induced by D-enantiomers, and sequentially switching between amino-acid enantiomers causes a switch in chirality. Nanoparticle tilting after binding of chiral amino acids is proposed as a chiral growth mechanism, where a ‘mother’ subunit nanoparticle spawns a slightly tilted, consequential ‘daughter’ nanoparticle, which by amplification over various length scales creates oriented mineral platelets and chiral vaterite suprastructures. These findings suggest a molecular mechanism for how biomineralization-related enantiomers might exert hierarchical control to form extended chiral suprastructures.
Obestatin stimulates glucose-induced insulin secretion through ghrelin receptor GHS-R
Authors: Pradhan Geetali , Wu Chia-Shan , Han Lee Jong , Kanikarla Preeti , Guo Shaodong , Yechoor Vijay K. , Samson Susan L. , Sun Yuxiang
Published: April 2017

Orexigenic hormone ghrelin and anorexic hormone obestatin are encoded by the same preproghrelin gene. While it is known that ghrelin inhibits glucose-stimulated insulin secretion (GSIS), the effect of obestatin on GSIS is unclear. Ghrelin’s effect is mediated by its receptor Growth Hormone Secretagogue Receptor (GHS-R), but the physiologically relevant receptor of obestatin remains debatable. Here we have investigated the effect of obestatin on GSIS in vitro, in vivo and ex vivo, and tested whether obestatin regulates insulin secretion through GHS-R. We found that under hyperglycemic condition, obestatin augments GSIS in rat insulinoma cells (INS-1) and in pancreatic islets from ghrelin−/− mice. Surprisingly, obestatin-induced GSIS was absent in β-cells in which GHS-R was suppressed. Obestatin-induced insulin secretion was abolished in the circulation of Ghsr−/− mice, and in pancreatic islets isolated from Ghsr−/− mice. We also found that obestatin-induced GSIS was attenuated in islets isolated from β-cell-specific Ghsr knockout MIP-Cre/ERT;Ghsrf/f mice. Our data collectively demonstrate that obestatin is a potent insulin secretagogue under hyperglycemic condition, and obestatin’s effect on insulin secretion is mediated by GHS-R in pancreatic β-cells. Our findings reveal an intriguing insight that obestatin and ghrelin have opposing effects on insulin secretion, and both are mediated through ghrelin receptor GHS-R.
Growth Differentiation Factor-15 Deficiency Augments Inflammatory Response and Exacerbates Septic Heart and Renal Injury Induced by Lipopolysaccharide
Authors: Abulizi Palida , Loganathan Neruja , Zhao Duo , Mele Tina , Zhang Yixin , Zwiep Terry , Liu Kexiang , Zheng Xiufen
Published: April 2017

Septic acute kidney injury (AKI) and myocardial dysfunction are leading causes of mortality with no accepted method of therapy. In this study we demonstrate the role of growth differentiating factor 15 (GDF15) in septic AKI and myocardial dysfunction using a murine lipopolysaccharide (LPS)-induced sepsis model and anin vitrocell culture system. Data show that GDF15 deficiency augments inflammatory response and exacerbates renal and cardiac injury induced by LPS, while over-expression of GDF15 protects the kidney and heart from LPS-induced organ dysfunction. Therefore, this study highlights the therapeutic potential of GDF15 in the treatment of endotoxin-induced sepsis.
Tangluoning, a traditional Chinese medicine, attenuates in vivo and in vitro diabetic peripheral neuropathy through modulation of PERK/Nrf2 pathway
Authors: Yang Xinwei , Yao Weijie , Liu Haolong , Gao Yanbin , Liu Renhui , Xu Liping
Published: April 2017

Prolonged hyperglycemia-induced oxidative stress and endoplasmic reticulum stress have been demonstrated to play a key role in progression of diabetic peripheral neuropathy (DPN). PERK/ Nrf2 pathway plays a predominant role in oxidative and endoplasmic reticulum (ER) stress which is associated with cell survival. This study examined the modulation of the PERK/Nrf2 pathway and apoptosis by a traditional Chinese medicine Tangluoning (TLN) in streptozotocin-induced DPN rat models and the effects of serum TLN on the PERK/Nrf2 pathway, apoptosis, intracellular reactive oxygen species and mitochondrial membrane potential in Schwann cells cultured in 150 mM glucose. It is found that TLN attenuated oxidative and ER stress and apoptosis through the PERK/Nrf2 pathway by upregulating p-PERK, Nrf2/ARE pathways and downregulating the CHOP-related apoptosis pathways in the experimental DPN models both in vivo and in vitro.
Hinge-deleted IgG4 blocker therapy for acetylcholine receptor myasthenia gravis in rhesus monkeys
Authors: Losen Mario , Labrijn Aran F. , van Kranen-Mastenbroek Vivianne H. , Janmaat Maarten L. , Haanstra Krista G. , Beurskens Frank J. , Vink Tom , Jonker Margreet , ‘t Hart Bert A. , Mané-Damas Marina , Molenaar Peter C. , Martinez-Martinez Pilar , van der Esch Eline , Schuurman Janine , de Baets Marc H. , Parren Paul W. H. I.
Published: April 2017

Autoantibodies against ion channels are the cause of numerous neurologic autoimmune disorders. Frequently, such pathogenic autoantibodies have a restricted epitope-specificity. In such cases, competing antibody formats devoid of pathogenic effector functions (blocker antibodies) have the potential to treat disease by displacing autoantibodies from their target. Here, we have used a model of the neuromuscular autoimmune disease myasthenia gravis in rhesus monkeys (Macaca mulatta) to test the therapeutic potential of a new blocker antibody: MG was induced by passive transfer of pathogenic acetylcholine receptor-specific monoclonal antibody IgG1-637. The effect of the blocker antibody (IgG4Δhinge-637, the hinge-deleted IgG4 version of IgG1-637) was assessed using decrement measurements and single-fiber electromyography. Three daily doses of 1.7 mg/kg IgG1-637 (cumulative dose 5 mg/kg) induced impairment of neuromuscular transmission, as demonstrated by significantly increased jitter, synaptic transmission failures (blockings) and a decrease in the amplitude of the compound muscle action potentials during repeated stimulations (decrement), without showing overt symptoms of muscle weakness. Treatment with three daily doses of 10 mg/kg IgG4Δhinge-637 significantly reduced the IgG1-637-induced increase in jitter, blockings and decrement. Together, these results represent proof-of principle data for therapy of acetylcholine receptor-myasthenia gravis with a monovalent antibody format that blocks binding of pathogenic autoantibodies.
Network-aided Bi-Clustering for discovering cancer subtypes
Authors: Yu Guoxian , Yu Xianxue , Wang Jun
Published: April 2017

Bi-clustering is a widely used data mining technique for analyzing gene expression data. It simultaneously groups genes and samples of an input gene expression data matrix to discover bi-clusters that relevant samples exhibit similar gene expression profiles over a subset of genes. The discovered bi-clusters bring insights for categorization of cancer subtypes, gene treatments and others. Most existing bi-clustering approaches can only enumerate bi-clusters with constant values. Gene interaction networks can help to understand the pattern of cancer subtypes, but they are rarely integrated with gene expression data for exploring cancer subtypes. In this paper, we propose a novel method called Network-aided Bi-Clustering (NetBC). NetBC assigns weights to genes based on the structure of gene interaction network, and it iteratively optimizes sum-squared residue to obtain the row and column indicative matrices of bi-clusters by matrix factorization. NetBC can not only efficiently discover bi-clusters with constant values, but also bi-clusters with coherent trends. Empirical study on large-scale cancer gene expression datasets demonstrates that NetBC can more accurately discover cancer subtypes than other related algorithms.
Phenome-wide association study for CYP2A6 alleles: rs113288603 is associated with hearing loss symptoms in elderly smokers
Authors: Polimanti Renato , Jensen Kevin P. , Gelernter Joel
Published: April 2017

To identify novel phenotypic associations related to Cytochrome P450 Family 2 Subfamily A Member 6 (CYP2A6), we investigated the human phenome in a total of 11,271 individuals. Initially, we conducted a phenome-wide association study in 3,401 nicotine-exposed elderly subjects considering 358 phenotypic traits. We identified a significant association between CYP2A6 rs113288603 and hearing loss symptoms (p = 5.75 × 10−5). No association was observed in a sample of 3,245 nicotine-unexposed individuals from the same discovery cohort, consistent with the conclusion that the finding is related to CYP2A6 involvement in nicotine metabolism. Consistent results were obtained (p < 0.1) in an independent sample of 2,077 nicotine-exposed elderly subjects, and similarly, no significance was observed in the nicotine-unexposed sample (n = 2,548) of the replication cohort. Additional supporting evidence for this association was provided by gene expression data: rs113288603 is associated with increased CYP2A6 expression in cerebellar hemispheres (p = 7.8 × 10−4). There is a well-known correlation between smoking and age-related hearing loss. Cigarette smoking is associated with structural changes in the brain and CYP2A6 mediates these changes. In this context, the regulatory role of rs113288603 in cerebellum appears to be consistent with the known involvement of this brain region in auditory function.
Experimental evidence of Fano resonances in nanomechanical resonators
Authors: Stassi Stefano , Chiadò Alessandro , Calafiore Giuseppe , Palmara Gianluca , Cabrini Stefano , Ricciardi Carlo
Published: April 2017

Fano resonance refers to an interference between localized and continuum states that was firstly reported for atomic physics and solid-state quantum devices. In recent years, Fano interference gained more and more attention for its importance in metamaterials, nanoscale photonic devices, plasmonic nanoclusters and surface-enhanced Raman scattering (SERS). Despite such interest in nano-optics, no experimental evidence of Fano interference was reported up to now for purely nanomechanical resonators, even if classical mechanical analogies were referred from a theoretical point of view. Here we demonstrate for the first time that harmonic nanomechanical resonators with relatively high quality factors, such as cantilevers vibrating in vacuum, can show characteristic Fano asymmetric curves when coupled in arrays. The reported findings open new perspectives in fundamental aspects of classical nanomechanical resonators and pave the way to a new generation of chemical and biological nanoresonator sensors with higher parallelization capability.
Affinity biosensors using recombinant native membrane proteins displayed on exosomes: application to botulinum neurotoxin B receptor
Authors: Desplantes Richard , Lévêque Christian , Muller Benjamin , Lotierzo Manuela , Ferracci Géraldine , Popoff Michel , Seagar Michael , Mamoun Robert , El Far Oussama
Published: April 2017

The development of simple molecular assays with membrane protein receptors in a native conformation still represents a challenging task. Exosomes are extracellular vesicles which, due to their stability and small size, are suited for analysis in various assay formats. Here, we describe a novel approach to sort recombinant fully native and functional membrane proteins to exosomes using a targeting peptide. Specific binding of high affinity ligands to the potassium channel Kv1.2, the G-protein coupled receptor CXCR4, and the botulinum neurotoxin type B (BoNT/B) receptor, indicated their correct assembly and outside out orientation in exosomes. We then developed, using a label-free optical biosensor, a new method to determine the kinetic constants of BoNT/B holotoxin binding to its receptor synaptotagmin2/GT1b ganglioside (kon = 2.3 ×105 M−1.s−1, koff = 1.3 10−4 s−1), yielding an affinity constant (KD = 0.6 nM) similar to values determined from native tissue. In addition, the recombinant binding domain of BoNT/B, a potential vector for neuronal delivery, bound quasi-irreversibly to synaptotagmin 2/GT1b exosomes. Engineered exosomes provide thus a novel means to study membrane proteins for biotechnology and clinical applications.
Orbital angular momentum (OAM) conversion and multicasting using N-core supermode fiber
Authors: Shao Guang-hao , Yan Shao-cheng , Luo Wei , Lu Guo-Wei , Lu Yan-qing
Published: April 2017

We propose and numerically demonstrate a conversion and multicasting scheme of orbital angular momentum (OAM) states by using N-core supermode fiber (NCSF), where the topological charges of converted OAM states mainly depend on the injected OAM state and the number of fiber cores. The conversion efficiency (CE) of the converted OAM states could be optimized by properly designing the fiber structure. Take N = 6 as an example, ~37% CE could be achieved at telecom bands. Moreover, even for a fabricated NCSF, the CE could be dynamically changed by stretching the fiber or by adjusting the refractive index of the fiber cores through external control of the environmental conditions. Meanwhile, OAM multicasting could also be realized in the designed NCSF. The crosstalk between the multicasted OAM channels and their neighboring ones are assessed to be less than −30 dB. The proposed fiber-based OAM conversion and multicasting system is compatible with the existing optical fiber communication systems, showing potential applications in the future.
Distant Phe345 mutation compromises the stability and activity of Mycobacterium tuberculosis isocitrate lyase by modulating its structural flexibility
Authors: Shukla Harish , Shukla Rohit , Sonkar Amit , Pandey Tripti , Tripathi Timir
Published: April 2017

Isocitrate lyase (ICL), a potential anti-tubercular drug target, catalyzes the first step of the glyoxylate shunt. In the present investigation, we studied the conformational flexibility of MtbICL to better understand its stability and catalytic activity. Our biochemical results showed that a point mutation at Phe345, which is topologically distant (>10 Å) to the active site signature sequence (189KKCGH193), completely abolishes the activity of the enzyme. In depth computational analyses were carried out for understanding the structural alterations using molecular dynamics, time-dependent secondary structure and principal component analysis. The results showed that the mutated residue increased the structural flexibility and induced conformational changes near the active site (residues 170–210) and in the C-terminal lid region (residues 411–428). Both these regions are involved in the catalytic activity of MtbICL. Upon mutation, the residual mobility of the enzyme increased, resulting in a decrease in the stability, which was confirmed by the lower free energy of stabilization in the mutant enzyme suggesting the destabilization in the structure. Our results have both biological importance and chemical novelty. It reveals internal dynamics of the enzyme structure and also suggests that regions other than the active site should be exploited for targeting MtbICL inhibition and development of novel anti-tuberculosis compounds.
Functional ectopic neuritogenesis by retinal rod bipolar cells is regulated by miR-125b-5p during retinal remodeling in RCS rats
Authors: Fu Yan , Hou Baoke , Weng Chuanhuang , Liu Weiping , Dai Jiaman , Zhao Congjian , Yin Zheng Qin
Published: April 2017

Following retinal degeneration, retinal remodeling can cause neuronal microcircuits to undergo structural alterations, which particularly affect the dendrites of bipolar cells. However, the mechanisms and functional consequences of such changes remain unclear. Here, we used Royal College of Surgeon (RCS) rats as a model of retinal degeneration, to study structural changes in rod bipolar cells (RBCs) and the underlying mechanisms of these changes. We found that, with retinal degeneration, RBC dendrites extended into the outer nuclear layer (ONL) of the retina, and the ectopic dendrites formed synapses with the remaining photoreceptors. This ectopic neuritogenesis was associated with brain-derived neurotrophic factor (BDNF) – expression of which was negatively regulated by miR-125b-5p. Overexpression of miR-125b-5p in the retinae of RCS rats diminished RBC ectopic dendrites, and compromised the b-wave of the flash electroretinogram (ERG). In contrast, down-regulation of miR-125b-5p (or exogenous BDNF treatment) increased RBC ectopic dendrites, and improved b-wave. Furthermore, we showed that the regulation of ectopic neuritogenesis by BDNF occurred via the downstream modulation of the TrkB-CREB signaling pathway. Based on these findings, we conclude that ectopic dendrites are likely to be providing functional benefits and that, in RCS rats, miR-125b-5p regulates ectopic neuritogenesis by RBCs through modulation of the BDNF-TrkB-CREB pathway. This suggests that therapies that reduce miR-125b-5p expression could be beneficial in human retinal degenerative disease.