bluuebunny/crossref_metadata_2025 huggingface dataset:
Examination of the relationship between phone usage and smartphone addiction based on certain variables
Authors: Arnavut Ahmet , Nuri Cahit , Direktor Cemaliye
Published: October 2018

Purpose: The purpose of the study is to investigate the relationship between technology usage and Smartphone addiction according to certain variables. Method: In this study, which was conducted with the purpose of determining the opinions of preservice teachers, a scanning model was employed. The sample of the study consists of 714 preservice teachers who studied at the Atatürk Education Faculty of Near East University, who were selected based on a random sampling method. In the study, a demographic information form prepared by the researchers was used in order to obtain the required data. The preservice teachers who participated in the study voluntarily were asked to provide information on their demographic features such as age and gender, period of using social networking sites, daily usage habits of smartphones, daily average time spent on social networking sites, average time spent using technological devices and their reasons for using smartphones. The Smartphone Addiction Scale Short Form adapted to the Turkish language by Noyan, Darcin, Nurmedov, Yılmaz and Dilbaz, (2015)and the Opinion Scale for Technological Device Usage developed by Arnavut and Bicen, (2013)  were both used. Findings: The conducted multiple regression analysis showed that the role of technology in life, communication and the usage of social media were significant predictor of smartphone addiction (F (3.709) = 282.065, p<.001). According to the obtained results, it was seen that the total variance explained 54% (R=.74, R2=.54, p<.001).A significant difference was observed in the communication dimension according to the age variable of the research (p=0.02), whereas no significant difference was found between smartphone addiction, social media usage and the role of technology in life (p<0.05). Tukey test analysis showed that the communication score increased with age. Conclusion: According to the obtained conclusions, it was found out that males predominantly use smartphones for communication purposes. No significant difference was found in terms of smartphone addiction. A high and significant relationship was found in a positive direction between smartphone addiction and social media usage. Additionally, a medium and significant relationship in a positive direction was found between smartphone addiction and the role of technology in life.
A scaled‐down neural conversational model for chatbots
Authors: Mathur Saurabh , Lopez Daphne
Published: October 2018

Deep learning has revolutionized the field of conversation modeling. A lot of the research has been toward making the conversational agent more human‐like. As a result, overall the model size increases. Bigger models require more data and are costly to build and maintain. Often, for some tasks, high‐quality responses are not necessary. In this paper, a model that consumes fewer resources and a way to augment conversation data without increasing the size of the vocabulary is proposed. The proposed model uses a modified version of the GRU instead of the LSTM to encode and decode sequences of text.
The large D black hole dynamics in AdS/dS backgrounds
Authors: Bhattacharyya Sayantani , Biswas Parthajit , Chakrabarty Bidisha , Dandekar Yogesh , Dinda Anirban
Published: October 2018

Abstract

We have constructed a class of perturbative dynamical black hole solutions in presence of cosmological constant. We have done our calculation in large number of dimensions. The inverse power of dimension has been used as the perturbation parameter and our calculation is valid upto the first subleading order. The solutions are in one to one correspondence with a dynamical membrane and a velocity field embedded in the asymptotic geometry. Our method is manifestly covariant with respect to the asymptotic geometry. One single calculation and the same universal result works for both dS and AdS geometry or in case of AdS for both global AdS and Poincare patch. We have checked our final answer with various known exact solutions and the known spectrum of Quasi Normal modes in AdS/dS.
Dual functions of microglia in the formation and refinement of neural circuits during development
Authors: Konishi Hiroyuki , Kiyama Hiroshi , Ueno Masaki
Published: October 2018

Microglia colonize the central nervous system (CNS) parenchyma during embryogenesis and contribute to various developmental processes leading to the formation of refined neural circuits. In this review, we focus on the bidirectional function of microglia during normal CNS development and discuss recent perspectives on the functions of microglia in neural circuit formation. Microglia participate in neurogenesis, migration, axonal growth, and synapse formation and remodeling, all of which are fundamental for the establishment of neural networks, by secreting a variety of molecules toward neurons and phagocytosing both live and dying neurons or their debris. Intriguingly, microglia play dual roles in each of the neurodevelopmental processes that they affect. For instance, microglia modulate synapse numbers by both promoting the formation of new synapses and eliminating unnecessary synapses. The study of the developmental roles of microglia is essential not only for understanding normal CNS development but also for preventing developmental brain disorders caused by microglial dysfunction.
Constitutional Incrementalism in a Religiously Divided Society: A Case Study of Afghanistan
Authors: PASARLAY Shamshad
Published: October 2018

This article explores the constitutional provisions that define the role of Islam and the shariah in Afghanistan’s many constitutions. It highlights that successful Afghan constitutions have always recognized Islam and the shariah and established a method of realizing them, while leaving open the possibility that the government could change its approach to realizing them in the future. Unsuccessful Afghan constitutions, by contrast, have allowed actors at the center to try to realize and interpret Islam in a rigid way that does not allow for ongoing negotiations with actors who would prefer to realize and interpret Islam in a different manner. In other words, Afghanistan’s longest-lived and successful constitutions have not entrenched Islam in a way that imposes the desires of one side of the debate. Instead, they have designed religious provisions in vague and ambiguous terms, thereby deferring to the future the question of what Islam really means and how it should be realized in practice – a strategy that proved considerably effective in preventing conflict over the role of Islam in a severely divided and heavily armed society. Drawing on this insight, the article explores how in overwhelmingly, but diversely, Muslim societies, it is important to create constitutional regimes that recognize Islam but leave room for rival interpretations of Islam. Incremental constitution writing is a useful tool in creating such constitutional regimes.
Improving pilot project application and review processes: A novel application of lean six sigma in translational science
Authors: Schmidt Susanne , Shay Laura Aubree , Saygin Can , Wan Hung-da , Schulz Karen , Clark Robert A. , Shireman Paula K.
Published: October 2018

Each year our Clinical and Translational Science Award pilot projects program awards approximately $500,000 in translational pilot funding to advance health in South Texas. We identified needs to improve the timeliness, transparency, and efficiency of the review process by surveying applicants. Lean six sigma methodologies, following a “Define, Measure, Analyze, Improve, Control” approach, were used to streamline the pilot project application and review by identifying and removing bottlenecks from process flows. We evaluated the impact of our reorganized review process by surveying applicants and reviewers. Process mapping identified pilot project review as the main source of delay, leading to the implementation of a study section-style review mechanism. After one cycle, 90.3% of pilot applicants and 100% of reviewers were highly satisfied with the new processes and time to award notice was reduced by 2 months. All reviewers familiar with both review processes preferred the study section. We demonstrated how lean six sigma, a methodology not commonly applied in research administration, can be used to evaluate processes in translational science in academic health centers. Through our efforts, we were able to improve timeliness, transparency, and efficiency of the review process.
Characteristic length scales of strongly rotating Boussinesq flow in variable-aspect-ratio domains
Authors: Zhai X. M. , Kurien Susan
Published: October 2018

We quantify the variability of the characteristic length scales of isotropically forced Boussinesq flows with stratification and frame rotation, as functions of the ratio $N/f$ of the Brunt–Väisälä frequency to the Coriolis frequency. The parameter ranges $0<N<f$, domain aspect ratio $1\leqslant \unicode[STIX]{x1D6FF}_{d}\leqslant 32$ and Burger number $Bu=\unicode[STIX]{x1D6FF}_{d}N/f\leqslant 1$ are explored for two values of $f$, one resulting in linear potential vorticity and the other in nonlinear potential vorticity. Characteristic length scales of the wave and vortical linear eigenmodes are separately quantified using $n$th-order spectral moments in both horizontal and vertical directions, for integer $n\leqslant 3$. In flows with linear potential vorticity, the horizontal vortical length scale $L_{0}$, characterizing a typical width of columnar structures, grows as ${\sim}(N/f)^{1/2}$ at all orders of $n$, regardless of domain aspect ratio. In unit-aspect-ratio domains, when intermediate scales are measured by filtering out the largest scales and using higher-order moments $n>1$, the vortical-mode aspect ratio $\unicode[STIX]{x1D6FF}_{0}$ asymptotes to a scaling of ${\sim}(N/f)^{-1}$, in agreement with quasi-geostrophic estimates. In contrast, the $\unicode[STIX]{x1D6FF}_{0}$ in tall-aspect-ratio domain flows yields a decay rate of at most ${\sim}(N/f)^{-1/2}$ after large-scale filtering. Flows with nonlinear potential vorticity display consistently weaker dependence of the characteristic scales on $N/f$ than the corresponding ones with linear potential vorticity. The wave-mode aspect ratios for all flows are essentially independent of $N/f$. We highlight the differences of these flow structure scalings relative to those expected for quasi-geostrophic flows, and those observed in strongly stratified, non-quasi-geostrophic flows.
Late Permian conchostracans (Crustacea, Branchiopoda) from continental deposits in the Moscow Syneclise, Russia
Authors: Scholze Frank , Golubev Valeriy K. , Niedźwiedzki Grzegorz , Schneider Joerg W. , Sennikov Andrey G.
Published: October 2018

The Moscow Syneclise on the East European Platform is an important area for the study of the continental biota of late Permian to Early Triassic age in continuous sections. This study attempts a taxonomic description of the late Permian conchostracan fauna of this area. The rich, new material was collected, bed by bed, during geological and paleontological excavations of lacustrine and fluvial deposits of the Obnora Formation and Vokhma Formation of the late Permian Zhukovian Regional Stage near the towns of Vyazniki and Gorokhovets. The conchostracan fauna of the Zhukovian Regional Stage consists predominantly ofPseudestheriaand less frequently ofPalaeolimnadiopsis. In the earliest Triassic Vokhmian Regional Stage, a more diverse fauna includingEuestheria,Magniestheria,Cornia,Palaeolimnadiopsis, andRossolimnadiopsiswas already recorded. The preliminary taxonomic determination of the pseudestheriids from the Zhukovian Regional Stage is intended to serve as a prerequisite for future studies of late Permian conchostracan biostratigraphy on the regional to interregional scale.
GENERALIZED LAMBERT SERIES, RAABE’S COSINE TRANSFORM AND A GENERALIZATION OF RAMANUJAN’S FORMULA FOR
Authors: DIXIT ATUL , GUPTA RAJAT , KUMAR RAHUL , MAJI BIBEKANANDA
Published: October 2018

A comprehensive study of the generalized Lambert series$\sum _{n=1}^{\infty }\frac{n^{N-2h}\text{exp}(-an^{N}x)}{1-\text{exp}(-n^{N}x)},00$,$N\in \mathbb{N}$and$h\in \mathbb{Z}$, is undertaken. Several new transformations of this series are derived using a deep result on Raabe’s cosine transform that we obtain here. Three of these transformations lead to two-parameter generalizations of Ramanujan’s famous formula for$\unicode[STIX]{x1D701}(2m+1)$for$m>0$, the transformation formula for the logarithm of the Dedekind eta function and Wigert’s formula for$\unicode[STIX]{x1D701}(1/N),N$even. Numerous important special cases of our transformations are derived, for example, a result generalizing the modular relation between the Eisenstein series$E_{2}(z)$and$E_{2}(-1/z)$. An identity relating$\unicode[STIX]{x1D701}(2N+1),\unicode[STIX]{x1D701}(4N+1),\ldots ,\unicode[STIX]{x1D701}(2Nm+1)$is obtained for$N$odd and$m\in \mathbb{N}$. In particular, this gives a beautiful relation between$\unicode[STIX]{x1D701}(3),\unicode[STIX]{x1D701}(5),\unicode[STIX]{x1D701}(7),\unicode[STIX]{x1D701}(9)$and$\unicode[STIX]{x1D701}(11)$. New results involving infinite series of hyperbolic functions with$n^{2}$in their arguments, which are analogous to those of Ramanujan and Klusch, are obtained.
Biology and life history ofLema praeusta(Fab.) (Coleoptera: Chrysomelidae), a biocontrol agent of two Commelinaceae weeds,Commelina benghalensisandMurdannia nudiflora
Authors: Das S. , Koner A. , Barik A.
Published: October 2018

We examined previous reports ofLema praeusta(Fab.) (Coleoptera: Chrysomelidae) as a minor pest of turmeric, eggplant, bottle gourd and pumpkin leaves, but no feeding damage by larvae and adults ofL. praeustawere recorded by us on these leaves. We observed feeding by the larvae and adults ofL. praeustaon ten species of Commelinaceae plants in no-choice tests. The biology, fecundity and life table parameters ofL. praeustaon two Commelinaceae weeds,Commelina benghalensisL. andMurdannia nudiflora(L.) Brenan were determined under laboratory conditions (27 ± 1°C, 65 ± 5% RH and 12L:12D). Total larval development times ofL. praeustawere 6.36 ± 0.07 and 7.28 ± 0.11 days (mean ± SE) onC. benghalensisandM. nudiflora, respectively. Adult females lived 106.25 ± 1.17 and 77.65 ± 0.91 days (mean ± SE) onC. benghalensisandM. nudiflora, respectively. Each female laid 272.95 ± 2.39 and 224 ± 1.74 eggs (mean ± SE) during a lifetime onC. benghalensisandM. nudiflora, respectively. The net reproductive rate (Ro), intrinsic rate of increase (rm), generation time (Tc), doubling time (DT) and finite rate of increase (λ) were 136.48, 0.14, 36.17, 5.10 and 1.41 onC. benghalensis, respectively, whereasRo,rm,Tc,DTand λ were 112, 0.20, 23.64, 3.47 and 1.51 onM. nudiflora, respectively, suggesting thatL. praeustacould be a potential biocontrol agent againstC. benghalensisandM. nudiflorain the fields of rice, maize, sorghum, soybean, mung bean, peanut and cotton.
Paths of Duty: Religion, Marriage, and the Press in a Transatlantic Scandal, 1835–1858
Authors: KRIVULSKAYA SUZANNA
Published: October 2018

When the Rev. Pierce Connelly denounced Protestantism and converted to Catholicism in 1835, he inadvertently started a small newspaper war among the burgeoning religious press in America. While Catholic periodicals celebrated their newest addition in print, Protestant newspapermen were scandalized. They worried about how the clerical husband's conversion might affect his marital life should he pursue ordination in the Catholic Church. Soon, the Connellys dissolved their marriage in Rome and moved to England, where Pierce became a priest, and his wife Cornelia entered a convent. When, thirteen years later, Pierce reconverted and sued Cornelia “for the restoration of conjugal rights” in an English court, the case became an international sensation – with both British and American newspapers covering the developments and using the saga to comment on larger religious and political issues of their time. The two scandals demonstrate how the transatlantic press debated contested global concerns about the limits of religious freedom, the changing nature of marriage, church–state relations, and international law.
Subversive skylines: local history and the rise of the Sayyids in Mongol Yazd
Authors: Mancini-Lander Derek J.
Published: October 2018

This article examines the emergence of the Ḥusaynī sayyids as key facilitators of the Mongols’ acculturation to Islamo-Persianate society and traces the expansion of their influence at imperial courts through the seventeenth century. Previous scholarship has emphasized the pivotal role of figures like Rashīduddīn Hamadānī in brokering reciprocal processes of acculturation from the empire's centre. This study builds on such work by shifting the focus to Yazd, a provincial city. It explores the evolving and unique role of Yazdī sayyids in facilitating such processes as they fashioned new patronage networks at court and reconfigured the urban morphology of Yazd. Furthermore, using local histories alongside universal ones, this study explores narrative strategies by which Yazdī authors, writing after the Mongol period, commemorated the sayyids’ emergence. It situates these writings in the context of larger transformations that affected relations between provincial elites and the imperial centre throughout these periods.
PROTECTED PUBLICATIONS: THE IMPERIAL AND SAXON PRIVILEGES FOR PRINTED MUSIC, 1550–1700
Authors: Rose Stephen
Published: October 2018

In the decades around 1600 many privileges for printed music were issued by the Holy Roman Emperor and the Elector of Saxony. Such privileges gave a bookseller or author an exclusive right to publish specified works for a limited period (usually ten years). The privileges threatened confiscation of any unauthorised copies, and fines for anyone caught printing or selling them. This article offers the first systematic study of archival material documenting the privileges for music, as preserved in the Österreichisches Staatsarchiv, Vienna, and the Sächsisches Hauptstaatsarchiv, Dresden. It reconstructs the ritualistic procedure for obtaining a privilege, analyses how composers justified their applications for privileges, and asks whether privileges gave effective protection against unauthorised editions. Revising previous interpretations of the privilege system as an early form of copyright, I instead argue that privileges enhanced the commercial and symbolic value of printed music.
Brahms’s Sybel: The Politics and Practice of Prussian Nationalist History
Authors: Burford Mark
Published: October 2018

Johannes Brahms’s well-known historical consciousness took a particularly formative turn in the mid-1850s when he embarked upon a self-imposed hiatus from composing to deepen his knowledge of the music-historical past. This conscious embrace of historical study was characteristic of his time. Following the 1848Märzrevolution, a growing contingent of German intellectuals, sceptical of the more speculative teachings of philosophy and theology, became increasingly receptive to the concrete lessons of history. Brahms’s reading habits suggest his inclination toward a politics of historical knowledge closely associated with the ‘Prussian School’. The writings of these historians, including Johann Gustav Droysen, Henrich von Sybel and Heinrich von Treitschke, exhibit a blend of idealist philosophy and dogmatic empiricism oriented above all toward the goal of legitimating German national unification under Prussia. Particularly influential was Sybel’s seven-volumeDie Begründung des deutschen Reiches durch Wilhelm I(The Founding of the German Reich through Wilhelm I), completed in the 1890s. Brahms, a Hamburg-born sympathizer of PrussianKleindeutschnationalism, who was a permanent resident of the Austrian capital of Vienna for the last 26 years of his life, was uniquely situated in relationship to the ‘German Question’. His well-marked copy of Sybel’s magisterial text adds illuminating granularity to our understanding of his personal and political values and ruminations on history spanning four decades. Brahms’s reading of Sybel makes legible a longer trajectory stretching from his ‘years of study’ in the 1850s, conveying how the studious historicism of his youth is best understood as an aesthetic stance densely interwoven with, and at the end of his life ratified by, the cultural and political agendas of Prussian School ideology and the meanings of the past forged in the crucible of the German historical imagination.
Early and Middle Pleistocene environments, landforms and sediments in Scotland
Authors: HALL Adrian M. , MERRITT Jon W. , CONNELL E. Rodger , HUBBARD Alun
Published: October 2018

This paper reviews the changing environments, developing landforms and terrestrial stratigraphy during the Early and Middle Pleistocene stages in Scotland. Cold stages after 2.7 Ma brought mountain ice caps and lowland permafrost, but larger ice sheets were short-lived. The late Early and Middle Pleistocene sedimentary record found offshore indicates more than 10 advances of ice sheets from Scotland into the North Sea but only 4–5 advances have been identified from the terrestrial stratigraphy. Two primary modes of glaciation, mountain ice cap and full ice sheet modes, can be recognised. Different zones of glacial erosion in Scotland reflect this bimodal glaciation and the spatially and temporally variable dynamics at glacier beds. Depths of glacial erosion vary from almost zero in Buchan to hundreds of metres in glens in the western Highlands and in basins both onshore and offshore. The presence of tors and blockfields indicates repeated development of patches of cold-based, non-erosive glacier ice on summits and plateaux. In lowlands, chemical weathering continued to operate during interglacials, but gruss-type saprolites are mainly of Pliocene to Early Pleistocene age. The Middle Pleistocene terrestrial stratigraphic record in Scotland, whilst fragmentary and poorly dated, provides important and accessible evidence of changing glacial, periglacial and interglacial environments over at least three stadial–interstadial–interglacial cycles. The distributions of blockfields and tors and the erratic contents of glacial sediments indicate that the configuration, thermal regime and pattern of ice flow during MIS 6 were broadly comparable to those of the last ice sheet. Improved control over the ages of Early and Middle Pleistocene sediments, soils and saprolites and on long-term rates of weathering and erosion, combined with information on palaeoenvironments, ice extent and sea level, will in future allow development and testing of new models of Pleistocene tectonics, isostasy, sea-level change and ice sheet dynamics in Scotland.
Substructure imaging of heterogeneous nanomaterials with enhanced refractive index contrast by using a functionalized tip in photoinduced force microscopy
Authors: Jahng Junghoon , Yang Heejae , Lee Eun Seong
Published: October 2018

The opto-mechanical force response from light-illuminated nanoscale materials has been exploited in many tip-based imaging applications to characterize various heterogeneous nanostructures. Such a force can have two origins: thermal expansion and induced dipoles. The thermal expansion reflects the absorption of the material, which enables one to chemically characterize a material at the absorption resonance. The induced dipole interaction reflects the local refractive indices of the material underneath the tip, which is useful to characterize a material in the spectral region where no absorption resonance occurs, as in the infrared (IR)-inactive region. Unfortunately, the dipole force is relatively small, and the contrast is rarely discernible for most organic materials and biomaterials, which only show a small difference in refractive indices for their components. In this letter, we demonstrate that refractive index contrast can be greatly enhanced with the assistance of a functionalized tip. With the enhanced contrast, we can visualize the substructure of heterogeneous biomaterials, such as a polyacrylonitrile-nanocrystalline cellulose (PAN-NCC) nanofiber. From substructural visualization, we address the issue of the tensile strength of PAN-NCC fibers fabricated by several different mixing methods. Our understanding from the present study will open up a new opportunity to provide enhanced sensitivity for substructure mapping of nanobiomaterials, as well as local field mapping of photonic devices, such as surface polaritons on semiconductors, metals and van der Waals materials.
Genome-wide association study reveals novel genetic locus associated with intra-individual variability in response time
Authors: Pinar Ari , Hawi Ziarih , Cummins Tarrant , Johnson Beth , Pauper Marc , Tong Janette , Tiego Jeggan , Finlay Amy , Klein Marieke , Franke Barbara , Fornito Alex , Bellgrove Mark A.
Published: October 2018

Intra-individual response time variability (IIRTV) is proposed as a viable endophenotype for many psychiatric disorders, particularly attention-deficit hyperactivity disorder (ADHD). Here we assessed whether IIRTV was associated with common DNA variation genome-wide and whether IIRTV mediated the relationship between any associated loci and self-reported ADHD symptoms. A final data set from 857 Australian young adults (489 females and 368 males;Mage = 22.14 years, SDage = 4.82 years) who completed five response time tasks and self-reported symptoms of ADHD using the Conners’ Adult ADHD Rating Scale was used. Principal components analysis (PCA) on these response time measures (standard deviation of reaction times and the intra-individual coefficient of variation) produced two variability factors (labelled response selection and selective attention). To understand the genetic drivers of IIRTV we performed a genome-wide association analysis (GWAS) on these PCA-derived indices of IIRTV. For the selective attention variability factor, we identified one single-nucleotide polymorphism (SNP) attaining genome-wide significance; rs62182100 in theHDAC4gene located on chromosome 2q37. A bootstrapping mediation analysis demonstrated that the selective attention variability factor mediated the relationship between rs62182100 and self-reported ADHD symptoms. Our findings provide the first evidence of a genome-wide significant SNP association with IIRTV and support the potential utility of IIRTV as a valid endophenotype for ADHD symptoms. However, limitations of this study suggest that these observations should be interpreted with caution until replication samples become available.
GABAergic signaling linked to autophagy enhances host protection against intracellular bacterial infections
Authors: Kim Jin Kyung , Kim Yi Sak , Lee Hye-Mi , Jin Hyo Sun , Neupane Chiranjivi , Kim Sup , Lee Sang-Hee , Min Jung-Joon , Sasai Miwa , Jeong Jae-Ho , Choe Seong-Kyu , Kim Jin-Man , Yamamoto Masahiro , Choy Hyon E. , Park Jin Bong , Jo Eun-Kyeong
Published: October 2018

Gamma-aminobutyric acid (GABA) is the principal inhibitory neurotransmitter in the brain; however, the roles of GABA in antimicrobial host defenses are largely unknown. Here we demonstrate that GABAergic activation enhances antimicrobial responses against intracellular bacterial infection. Intracellular bacterial infection decreases GABA levels in vitro in macrophages and in vivo in sera. Treatment of macrophages with GABA or GABAergic drugs promotes autophagy activation, enhances phagosomal maturation and antimicrobial responses against mycobacterial infection. In macrophages, the GABAergic defense is mediated via macrophage type A GABA receptor (GABAAR), intracellular calcium release, and the GABA type A receptor-associated protein-like 1 (GABARAPL1; an Atg8 homolog). Finally, GABAergic inhibition increases bacterial loads in mice and zebrafish in vivo, suggesting that the GABAergic defense plays an essential function in metazoan host defenses. Our study identified a previously unappreciated role for GABAergic signaling in linking antibacterial autophagy to enhance host innate defense against intracellular bacterial infection.
Structural basis for PtdInsP2-mediated human TRPML1 regulation
Authors: Fine Michael , Schmiege Philip , Li Xiaochun
Published: October 2018

Transient receptor potential mucolipin 1 (TRPML1), a lysosomal channel, maintains the low pH and calcium levels for lysosomal function. Several small molecules modulate TRPML1 activity. ML-SA1, a synthetic agonist, binds to the pore region and phosphatidylinositol-3,5-bisphosphate (PtdIns(3,5)P2), a natural lipid, stimulates channel activity to a lesser extent than ML-SA1; moreover, PtdIns(4,5)P2, another natural lipid, prevents TRPML1-mediated calcium release. Notably, PtdIns(3,5)P2 and ML-SA1 cooperate further increasing calcium efflux. Here we report the structures of human TRPML1 at pH 5.0 with PtdIns(3,5)P2, PtdIns(4,5)P2, or ML-SA1 and PtdIns(3,5)P2, revealing a unique lipid-binding site. PtdIns(3,5)P2 and PtdIns(4,5)P2 bind to the extended helices of S1, S2, and S3. The phosphate group of PtdIns(3,5)P2 induces Y355 to form a π-cation interaction with R403, moving the S4–S5 linker, thus allosterically activating the channel. Our structures and electrophysiological characterizations reveal an allosteric site and provide molecular insight into how lipids regulate TRP channels.
Quantum machine learning for electronic structure calculations
Authors: Xia Rongxin , Kais Sabre
Published: October 2018

Considering recent advancements and successes in the development of efficient quantum algorithms for electronic structure calculations—alongside impressive results using machine learning techniques for computation—hybridizing quantum computing with machine learning for the intent of performing electronic structure calculations is a natural progression. Here we report a hybrid quantum algorithm employing a restricted Boltzmann machine to obtain accurate molecular potential energy surfaces. By exploiting a quantum algorithm to help optimize the underlying objective function, we obtained an efficient procedure for the calculation of the electronic ground state energy for a small molecule system. Our approach achieves high accuracy for the ground state energy for H2, LiH, H2O at a specific location on its potential energy surface with a finite basis set. With the future availability of larger-scale quantum computers, quantum machine learning techniques are set to become powerful tools to obtain accurate values for electronic structures.
Divergent wiring of repressive and active chromatin interactions between mouse embryonic and trophoblast lineages
Authors: Schoenfelder Stefan , Mifsud Borbala , Senner Claire E. , Todd Christopher D. , Chrysanthou Stephanie , Darbo Elodie , Hemberger Myriam , Branco Miguel R.
Published: October 2018

The establishment of the embryonic and trophoblast lineages is a developmental decision underpinned by dramatic differences in the epigenetic landscape of the two compartments. However, it remains unknown how epigenetic information and transcription factor networks map to the 3D arrangement of the genome, which in turn may mediate transcriptional divergence between the two cell lineages. Here, we perform promoter capture Hi-C experiments in mouse trophoblast (TSC) and embryonic (ESC) stem cells to understand how chromatin conformation relates to cell-specific transcriptional programmes. We find that key TSC genes that are kept repressed in ESCs exhibit interactions between H3K27me3-marked regions in ESCs that depend on Polycomb repressive complex 1. Interactions that are prominent in TSCs are enriched for enhancer–gene contacts involving key TSC transcription factors, as well as TET1, which helps to maintain the expression of TSC-relevant genes. Our work shows that the first developmental cell fate decision results in distinct chromatin conformation patterns establishing lineage-specific contexts involving both repressive and active interactions.
Graphene Oxide-Gold Nanosheets Containing Chitosan Scaffold Improves Ventricular Contractility and Function After Implantation into Infarcted Heart
Authors: Saravanan Sekaran , Sareen Niketa , Abu-El-Rub Ejlal , Ashour Hend , Sequiera Glen Lester , Ammar Hania I. , Gopinath Venkatraman , Shamaa Ashraf Ali , Sayed Safinaz Salah Eldin , Moudgil Meenal , Vadivelu Jamuna , Dhingra Sanjiv
Published: October 2018

Abnormal conduction and improper electrical impulse propagation are common in heart after myocardial infarction (MI). The scar tissue is non-conductive therefore the electrical communication between adjacent cardiomyocytes is disrupted. In the current study, we synthesized and characterized a conductive biodegradable scaffold by incorporating graphene oxide gold nanosheets (GO-Au) into a clinically approved natural polymer chitosan (CS). Inclusion of GO-Au nanosheets in CS scaffold displayed two fold increase in electrical conductivity. The scaffold exhibited excellent porous architecture with desired swelling and controlled degradation properties. It also supported cell attachment and growth with no signs of discrete cytotoxicity. In a rat model of MI, in vivo as well as in isolated heart, the scaffold after 5 weeks of implantation showed a significant improvement in QRS interval which was associated with enhanced conduction velocity and contractility in the infarct zone by increasing connexin 43 levels. These results corroborate that implantation of novel conductive polymeric scaffold in the infarcted heart improved the cardiac contractility and restored ventricular function. Therefore, our approach may be useful in planning future strategies to construct clinically relevant conductive polymer patches for cardiac patients with conduction defects.
MiR-323b-5p acts as a novel diagnostic biomarker for critical limb ischemia in type 2 diabetic patients
Authors: Cheng Biao , Li Ju-yi , Li Xiao-chao , Wang Xiu-fang , Wang Zhong-jing , Liu Jue , Deng Ai-ping
Published: October 2018

Type 2 diabetes mellitus (T2DM) is a major contributor to peripheral artery disease (PAD), especially in cases that advance to critical limb ischemia (CLI). Accumulating evidence indicates that miRNAs play an important role in the development of PAD and T2DM. Due to the limited value of current diagnostic methods for CLI in T2DM patients, we compared the miRNA expression profiles of Chinese T2DM patients with or without CLI to find out whether distinctive miRNAs could serve as potential diagnostic biomarkers. We statistically identified 7 miRNAs (hsa-miR-200b-3p, hsa-miR-2115-3p, hsa-miR-431-5p, hsa-miR-486-5p, hsa-miR-210-3p, hsa-miR-1264, hsa-miR-323b-5p) which were up-regulated in the CLI group, whereas other 4 miRNAs (hsa-miR-5579-3p, hsa-miR-665, hsa-miR-4285, hsa-miR-500a-3p) were down-regulated. Our validation test suggested a relatively high diagnostic accuracy of serum hsa-miR-323b-5p levels for the detection of CLI in T2DM patients, with a sensitivity of 62.67% and a specificity of 80.65%. The area under the curve (AUC) for miR-323b-5p + confounding risk factors was 0.94 (95% CI: 0.884–0.994, P < 0.001), which was higher than that for miR-323b-5p. Taken together, our results indicate that circulating hsa-miR-323b-5p could be a promising serum biomarker for the diagnosis of critical limb ischemia in type 2 diabetic patients.
High-Efficiency Reverse (5′→3′) Synthesis of Complex DNA Microarrays
Authors: Hölz Kathrin , Hoi Julia K. , Schaudy Erika , Somoza Veronika , Lietard Jory , Somoza Mark M.
Published: October 2018

DNA microarrays are important analytical tools in genetics and have recently found multiple new biotechnological roles in applications requiring free 3′ terminal hydroxyl groups, particularly as a starting point for enzymatic extension via DNA or RNA polymerases. Here we demonstrate the highly efficient reverse synthesis of complex DNA arrays using a photolithographic approach. The method is analogous to conventional solid phase synthesis but makes use of phosphoramidites with the benzoyl-2-(2-nitrophenyl)-propoxycarbonyl (BzNPPOC) photolabile protecting group on the 3′-hydroxyl group. The use of BzNPPOC, with more than twice the photolytic efficiency of the 2-(2-nitrophenyl)-propoxycarbonyl (NPPOC) previously used for 5′→3′ synthesis, combined with additional optimizations to the coupling and oxidation reactions results in an approximately 3-fold improvement in the reverse synthesis efficiency of complex arrays of DNA oligonucleotides. The coupling efficiencies of the reverse phosphoramidites are as good as those of regular phosphoramidites, resulting in comparable yields. Microarrays of DNA surface tethered on the 5′ end and with free 3′ hydroxyl termini can be synthesized quickly and with similarly high stepwise coupling efficiency as microarrays using conventional 3′→5′ synthesis.
Spiral magnetic domain structure in cylindrically-shaped microwires
Authors: Chizhik A. , Zhukov A. , Gonzalez J. , Gawroński P. , Kułakowski K. , Stupakiewicz A.
Published: October 2018

Identification and characterisation of novel and unusual magnetization states remains a topic of research in modern magnetism. Recently, control of the magnetization state between the surface and volume in cylindrical microwires with the giant magneto-impedance effect has been demonstrated. Herein, the phenomenon of spatial migration of spiral magnetic domains inside a microwire is demonstrated using the magneto-optical Kerr effect. The main properties of the inclined spiral structure were determined, where the surface domain structure possessed a length limited only by actual sample length. Transformation of the structure from a spiral to an elliptical structure could be controlled by external torsion stress. Hysteresis and magnetic images were simulated based on a model assuming a spatial distribution of the internal stress inside the microwire, whose results were consistent with the experimental results. A consistent interpretation of the results in terms of the formation and transformation of the spiral magnetic domain structure is proposed.
CX3CR1 differentiates F4/80low monocytes into pro-inflammatory F4/80high macrophages in the liver
Authors: Lee Young-Sun , Kim Myung-Ho , Yi Hyon-Seung , Kim So Yeon , Kim Hee-Hoon , Kim Ji Hoon , Yeon Jong Eun , Byun Kwan Soo , Byun Jin-Seok , Jeong Won-Il
Published: October 2018

The expression of chemokine receptor CX3CR1 is related to migration and signaling in cells of the monocyte-macrophage lineage. The precise roles of CX3CR1 in the liver have been investigated but not clearly elucidated. Here, we investigated the roles of CX3CR1 in hepatic macrophages and liver injury. Hepatic and splenic CX3CR1lowF4/80low monocytes and CX3CR1lowCD16− monocytes were differentiated into CX3CR1highF4/80high or CX3CR1highCD16+ macrophages by co-culture with endothelial cells. Moreover, CX3CL1 deficiency in human umbilical vein endothelial cells (HUVECs) attenuated the expression of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), whereas recombinant CX3CL1 treatment reversed this expression in co-cultured monocytes. Upon treatment with clodronate liposome, hepatic F4/80high macrophages were successfully depleted at day 2 and recovered similarly in CX3CR1+/GFP and CX3CR1GFP/GFP mice at week 4, suggesting a CX3CR1-independent replacement. However, F4/80high macrophages of CX3CR1+/GFP showed a stronger pro-inflammatory phenotype than CX3CR1GFP/GFP mice. In clodronate-treated chimeric CX3CR1+/GFP and CX3CR1GFP/GFP mice, CX3CR1+F4/80high macrophages showed higher expression of IL-1β and TNF-α than CX3CR1−F4/80high macrophages. In alcoholic liver injury, despite the similar frequency of hepatic F4/80high macrophages, CX3CR1GFP/GFP mice showed reduced liver injury, hepatic fat accumulation, and inflammatory responses than CX3CR1+/GFP mice. Thus, CX3CR1 could be a novel therapeutic target for pro-inflammatory macrophage-mediated liver injury.
Bone mineral density assessment using iterative reconstruction compared with quantitative computed tomography as the standard of reference
Authors: Mann Constanze , Ziegeler Katharina , Mews Jürgen , Plaschke Martina , Issever Ahi Sema
Published: October 2018

This study examines the influence of iterative reconstruction on bone mineral density (BMD) measurement by comparison with standard quantitative computed tomography (QCT; reference) and two other protocols based on filtered back projection. Ten human cadaver specimens of the lumbar spine with a hydroxyapatite calibration phantom underneath, were scanned with 4 protocols: 1. standard QCT, 2. volume scan with FBP, 3. helical scan with FBP, and 4. helical scan with IR (Adaptive Iterative Dose Reduction 3D (AIDR3D)). Radiation doses were recorded as CT dose index (CTDIvol) and BMD, signal-to-noise and contrast-to-noise ratio were calculated. Mean hydroxyapatite concentration (HOA) did not differ significantly between protocols, ranging from 98.58 ± 31.09 mg cm3 (protocol 4) to 100.47 ± 30.82 mg cm3 (protocol 2). Paired sample correlations of HOA values for protocol 4 and protocols 1, 2 and 3 were nearly perfect with coefficients of 0.980, 0.979 and 0.982, respectively (p < 0.004). CTDIvol were 7.50, 5.00, 6.82 (±2.03) and 1.72 (±0.50) mGy for protocols 1, 2, 3 and 4 respectively. Objective image quality was highest for protocol 4. The use of IR for BMD assessment significantly lowers radiation exposure compared to standard QCT and protocols with FBP while not degrading BMD measurement.
Mechanisms Underlying the Regulation of HP1γ by the NGF-PKA Signaling Pathway
Authors: Seo Seungmae , Mathison Angela , Grzenda Adrienne , Podratz Jewel , Calvo Ezequiel , Brimijoin Stephen , Windebank Anthony , Iovanna Juan , Lomberk Gwen , Urrutia Raul
Published: October 2018

Heterochromatin protein 1 γ (HP1γ) is a well-known chromatin protein, which regulates gene silencing during the execution of processes associated with embryogenesis, organ maturation, and cell differentiation. We find that, in vivo, the levels of HP1γ are downregulated during nervous system development. Similar results are recapitulated in vitro during nerve growth factor (NGF)-induced neuronal cell differentiation in PC12 cells. Mechanistically, our experiments demonstrate that in differentiating PC12 cells, NGF treatment decreases the association of HP1γ to silent heterochromatin, leads to phosphorylation of this protein at S83 via protein kinase A (PKA), and ultimately results in its degradation. Genome-wide experiments, using gain-of-function (overexpression) and loss-of-function (RNAi) paradigms, demonstrate that changing the level of HP1γ impacts on PC12 differentiation, at least in part, through gene networks involved in this process. Hence, inactivation of HP1γ by different post-translational mechanisms, including reduced heterochromatin association, phosphorylation, and degradation, is necessary for neuronal cell differentiation to occur. Indeed, we show that the increase of HP1γ levels has the reverse effect, namely antagonizing neuronal cell differentiation, supporting that this protein acts as a barrier for this process. Thus, these results describe the regulation and participation of HP1γ in a novel membrane-to-nucleus pathway, through NGF-PKA signaling, which is involved in NGF-induced neuronal cell differentiation.
Fast simultaneous quantitation of valsartan and amlodipine besylate using an eco-friendly micellar HPLC-UV method: application to spiked human plasma and content uniformity testing for amlodipine
Authors: Ibrahim Fawzia A. , El-Brashy Amina M. , El-Awady Mohamed I. , Abdallah Nora A.
Published: October 2018

A simple, sensitive, and economic quantitation of two co-formulated antihypertensive drugs, valsartan and amlodipine besylate was carried out in less than 4 minutes.
Two-dimensional electronic-vibrational spectroscopic study of conical intersection dynamics: an experimental and electronic structure study
Authors: Wu Eric C. , Ge Qinghui , Arsenault Eric A. , Lewis Nicholas H. C. , Gruenke Natalie L. , Head-Gordon Martin J. , Fleming Graham R.
Published: October 2018

The relaxation from the lowest singlet excited state of the triphenylmethane dyes, crystal violet and malachite green, is studied via two-dimensional electronic-vibrational (2DEV) spectroscopy.
Photoinduced energy transfer in carbazole–BODIPY dyads
Authors: Reddy Govind , Duvva Naresh , Seetharaman Sairaman , D’Souza Francis , Giribabu Lingamallu
Published: October 2018

A series of carbazole (CBZ)–boron dipyrromethene (BODIPY) based donor–acceptor dyads, CB1, CB2, and CB3, with CBZ as an energy donor, tethered together with spacers of varied sizes i.e., phenyl bridge, biphenyl bridge and diphenylethyne bridge, respectively, are reported.
Correction: Engineered hydrogen-bonded polymer multilayers: from assembly to biomedical applications
Authors: Such Georgina K. , Johnston Angus P. R. , Caruso Frank
Published: October 2018

Correction for ‘Engineered hydrogen-bonded polymer multilayers: from assembly to biomedical applications’ by Georgina K. Such et al., Chem. Soc. Rev., 2011, 40, 19–29.
Germylene–sulfoxide as a potential hemilabile ligand: application in coordination chemistry
Authors: Lentz Nicolas , Mallet-Ladeira Sonia , Baceiredo Antoine , Kato Tsuyoshi , Madec David
Published: October 2018

Heteroleptic organogermylenes containing a sulfoxide donor function were used for application in coordination chemistry with [W(cod)(CO)4], [Mo(nbd)(CO)4] and [Ru(PPh3)3Cl2].
The Achilles' heel of iron-based catalysts during oxygen reduction in an acidic medium
Authors: Choi Chang Hyuck , Lim Hyung-Kyu , Chung Min Wook , Chon Gajeon , Ranjbar Sahraie Nastaran , Altin Abdulrahman , Sougrati Moulay-Tahar , Stievano Lorenzo , Oh Hyun Seok , Park Eun Soo , Luo Fang , Strasser Peter , Dražić Goran , Mayrhofer Karl J. J. , Kim Hyungjun , Jaouen Frédéric
Published: October 2018

Exposing Fe–N–C catalysts to H2O2-byproduct leaves their catalytic sites untouched but decreases the turnover frequency via oxidation of the carbon surface.
Pd nanoparticles/polyoxometalate–ionic liquid composites on SiO2 as multifunctional catalysts for efficient production of ketones from diaryl ethers
Authors: Zhang Zhanrong , Liu Mingyang , Song Jinliang , Liu Huizhen , Xie Zhenbing , Liu Shuaishuai , Meng Qinglei , Zhang Pei , Han Buxing
Published: October 2018

Effective and selective transformation of diaryl ethers to value-added ketones.
Enhancement of optical resolution in three-dimensional refractive-index tomograms of biological samples by employing micromirror-embedded coverslips
Authors: Shin Seungwoo , Kim Jihye , Lee Je-Ryung , Jeon Eun-chae , Je Tae-Jin , Lee Wonhee , Park YongKeun
Published: October 2018

Resolution-enhanced optical diffraction tomography using a micromirror-embedded coverslips.
How to quantify isotropic negative thermal expansion: magnitude, range, or both?
Authors: Coates Chloe S. , Goodwin Andrew L.
Published: October 2018

Negative thermal expansion (NTE) is the counterintuitive material property of volume contraction on heating. We compare different systems with contrasting mechanisms for isotropic NTE using the metric of NTE capacity.
Porous tal palm carbon nanosheets: preparation, characterization and application for the simultaneous determination of dopamine and uric acid
Authors: Ahammad A. J. Saleh , Odhikari Noyon , Shah Syed Shaheen , Hasan Md. Mahedi , Islam Tamanna , Pal Poly Rani , Ahmed Qasem Mohammed Ameen , Aziz Md. Abdul
Published: October 2018

Porous tal palm carbon nanosheets were prepared, characterized and utilized for DA and UA sensing.
A bio-inspired physically transient/biodegradable synapse for security neuromorphic computing based on memristors
Authors: Dang Bingjie , Wu Quantan , Song Fang , Sun Jing , Yang Mei , Ma Xiaohua , Wang Hong , Hao Yue
Published: October 2018

Fully degradable biomimetic synaptic devices based on a W/MgO/ZnO/Mo memristor on a silk protein substrate show remarkable information storage and synaptic characteristics.
Non-invasive 19F NMR analysis of a protein-templated N-acylhydrazone dynamic combinatorial library
Authors: Ekström Alexander G. , Wang Jue Theresa , Bella Juraj , Campopiano Dominic J.
Published: October 2018

Dynamic combinatorial chemistry (DCC) is a powerful tool to identify ligands for biological targets.