bluuebunny/crossref_metadata_2025 huggingface dataset:
Experience and the Soul in Eighteenth-Century Medicine
Authors: Koch Philippa
Published: September 2016

Focused on three different protestant communities—puritans, pietists, and Methodists—this essay argues that eighteenth-century protestants were actively engaged in contemporary medical debates, and that their engagement was shaped by their faith in providence. Eighteenth-century protestants understood sickness as part of the created order, they interpreted medicine as a divinely-given tool for Christian action on behalf of the suffering, and they recognized an opportunity for mission in their healing efforts. Motivated by their understanding of God's providential oversight of sickness and health, they relied on empirical medicine, read widely in the emerging medical print culture, turned to networks of women's medical knowledge, and participated in theoretical debates over the soul's role in bodily health. This essay represents an important intervention both in medical history, which has overlooked or misunderstood the role of religion in eighteenth-century medical thought and practice, and in religious studies, in which studies of religion and medicine in America have focused almost exclusively on movements emerging since the nineteenth century and the rise of Arminianism.
The effects of stress–tension on depression and anxiety symptoms: evidence from a novel twin modelling analysis
Authors: Davey C. G. , López-Solà C. , Bui M. , Hopper J. L. , Pantelis C. , Fontenelle L. F. , Harrison B. J.
Published: September 2016

Background

Negative mood states are composed of symptoms of depression and anxiety, and by a third factor related to stress, tension and irritability. We sought to clarify the nature of the relationships between the factors by studying twin pairs.

Method

A total of 503 monozygotic twin pairs completed the Depression Anxiety Stress Scales (DASS), an instrument that assesses symptoms of depression, anxiety and stress–tension. We applied a recently developed twin regression methodology – Inference about Causation from Examination of FAmiliaL CONfounding (ICE FALCON) – to test for evidence consistent with the existence of ‘causal’ influences between the DASS factors.

Results

There was evidence consistent with the stress–tension factor having a causal influence on both the depression (p < 0.0001) and anxiety factors (p = 0.001), and for the depression factor having a causal influence on the anxiety factor (p < 0.001).

Conclusions

Our findings suggest a critical role for stress–tension in the structure of negative mood states, and that interventions that target it may be particularly effective in reducing depression and anxiety symptoms.
Robust task-space control of robot manipulators using differential equations for uncertainty estimation
Authors: Izadbakhsh Alireza , Khorashadizadeh Saeed
Published: September 2016

Most control algorithms for rigid-link electrically driven robots are given in joint coordinates. However, since the task to be accomplished is expressed in Cartesian coordinates, inverse kinematics has to be computed in order to implement the control law. Alternatively, one can develop the necessary theory directly in workspace coordinates. This has the disadvantage of a more complex robot model. In this paper, a robust control scheme is given to achieve exact Cartesian tracking without the knowledge of the manipulator kinematics and dynamics, actuator dynamics and nor computing inverse kinematics. The control design procedure is based on a new form of universal approximation theory and using Stone–Weierstrass theorem, to mitigate structured and unstructured uncertainties associated with external disturbances and actuated manipulator dynamics. It has been assumed that the lumped uncertainty can be modeled by linear differential equations. As the method is Model-Free, a broad range of manipulators can be controlled. Numerical case studies are developed for an industrial robot manipulator.
Vision-based obstacle avoidance system with fuzzy logic for humanoid
robots
Authors: Chiang Shu-Yin
Published: September 2016

This study presents the algorithm for a humanoid robot to accomplish an obstacle
run in the FIRA HuroCup competition. It includes the integration of image
processing and robot motion. DARwIn-OP (Dynamic Anthropomorphic Robot with
Intelligence–Open Platform) was used as the humanoid robot, and it is
equipped with a webcam as a vision system to obtain an image of what is in front
of the robot. Image processing skills such as erosion, dilation, and
eight-connected component labeling are applied to reduce image noise. Moreover,
we use navigation grids with filters to avoid the obstacles. Fuzzy logic rules
are used to implement the robot’s motion, allowing a humanoid robot to
access any routes using obstacle avoidance to perform the tasks in the
obstacle-run event.
Influence of war on hunting patterns and pressure in Sierra Leone
Authors: CONTEH ABU , GAVIN MICHAEL C.
Published: September 2016

Bushmeat hunting poses a huge challenge for biodiversity conservation, but bushmeat is also an important source of essential protein in many locations. Although war may have substantial impacts on hunting, how these effects vary across different spatial scales and over multiple stages of warfare remain largely unknown. In addition, despite serious conflicts that may have affected hunting patterns in West Africa, no studies have examined the impacts of war on hunting in Sierra Leone. We used the randomized response technique together with semi-structured interviews to examine variations in hunting techniques and the proportion of the population that engages in hunting over three time periods (before, during and after war) among different communities bordering a protected area. At the scale of the whole protected area, the proportion of people hunting did not vary significantly over time. Similarly, the methods used for hunting were generally consistent over time and space. However, within each community, the proportion of the population hunting varied significantly over time, and the locations with the greatest participation rates in hunting changed at each time period. Access to alternative livelihood options and the severity of the war's impact shaped patterns of change in hunting participation across different communities. Our results point to the importance of adaptive management approaches that can adjust management strategies in order to account for spatial or temporal variations in hunting behaviour.
Searching for Anglo-American Digital Legal History
Authors: Robertson Stephen
Published: September 2016

As the fields of digital humanities and digital history have grown in scale and visibility since the 1990s, legal history has largely remained on the margins of those fields. The move to make material available online in the first decade of the web featured only a small number of legal history projects: Famous Trials; Anglo-American Legal Tradition; The Proceedings of the Old Bailey Online, 1674–1913. Early efforts to construct hypertext narratives and scholarship also included some works of legal history: “Hearsay of the Sun: Photography, Identity and the Law of Evidence in Nineteenth-Century Courts,” in Hypertext Scholarship in American Studies; Who Killed William Robinson? and Gilded Age Plains City: The Great Sheedy Murder Trial and the Booster Ethos of Lincoln, Nebraska. In the second decade of the web, the focus shifted from distributing material to exploring it using digital tools. The presence of digital history grew at the meetings of organizations of historians ranging from the American Historical Association to the Urban History Association, but not at the American Society for Legal History conferences, the annual meetings of the Law and Society Association, or the British Legal History Conference. Only a few Anglo-American legal historians took up computational tools for sorting and visualizing sources such as data mining, text mining, and topic modeling; network analysis; and mapping. Paul Craven and Douglas Hay's Master and Servant project text mined a comprehensive database of 2,000 statutes and 1,200,000 words to explore similarities and influence among statutes. Data Mining with Criminal Intent mined and visualized the words in trial records using structured data from The Proceedings of the Old Bailey Online, 1674–1913. Locating London's Past, a project that mapped resources relating to the early modern and eighteenth century city, and also made use of the Old Bailey records. Digital Harlem mapped crime in the context of everyday life in the 1920s. Only in the past few years has more digital legal history using computational tools begun to appear, and like many of the projects discussed in this special issue, most remain at a preliminary stage. This article seeks to bring into focus the constraints, possibilities, and choices that shape digital legal history, in order to create a context for the work in this special issue, and to promote discussion of what it means to do legal history in the digital age.
Evaluierung individueller Trainingsvorgaben auf Basis der Herzfrequenzvariabilität für ein Lauftraining im Freizeit- und Gesundheitssport
Authors: Gronwald Thomas , Schulze Stephan , Ludyga Sebastian , Hottenrott Kuno
Published: September 2016

Zusammenfassung. Die Belastungssteuerung über die Herzfrequenzvariabilität (HRV) gewinnt im Kontext der Trainingsindividualisierung immer mehr an Bedeutung. Ziel der Studie war es, zu überprüfen, ob sich die über ein Herzfrequenzmessgerät auf der Basis der HRV ermittelten Intensitätsbereiche in Abhängigkeit der Leistungsfähigkeit über einen mehrwöchigen Trainingszyklus verändern. Freizeitläufer wurden für ein zwölfwöchiges Ausdauerprogramm rekrutiert. Vor und nach der Intervention wurde ein Stufentest mit Spirometrie durchgeführt. Zudem wurden die Belastungsvorgaben analysiert. Über den Interventionszeitraum hat sich die Unter- und Obergrenze der vorgegebenen Herzfrequenz in der niedrigsten Intensitätszone signifikant erhöht. Bezogen auf die Ausdauerleistung waren nach der Trainingsintervention zudem signifikante Verbesserungen zu verzeichnen. Die Anpassung der Herzfrequenzwerte an die veränderte Leistungsfähigkeit sichert in diesem Rahmen ein reizwirksames Training über eine mehrwöchige Trainingsintervention ab.
Thrombospondin-1 signaling through CD47 inhibits cell cycle progression and induces senescence in endothelial cells
Authors: Gao Qi , Chen Kexin , Gao Lu , Zheng Yang , Yang Yong-Guang
Published: September 2016

CD47 signaling in endothelial cells has been shown to suppress angiogenesis, but little is known about the link between CD47 and endothelial senescence. Herein, we demonstrate that the thrombospondin-1 (TSP1)-CD47 signaling pathway is a major mechanism for driving endothelial cell senescence. CD47 deficiency in endothelial cells significantly improved their angiogenic function and attenuated their replicative senescence. Lack of CD47 also suppresses activation of cell cycle inhibitors and upregulates the expression of cell cycle promoters, leading to increased cell cycle progression. Furthermore, TSP1 significantly accelerates replicative senescence and associated cell cycle arrest in a CD47-dependent manner. These findings demonstrate that TSP1-CD47 signaling is an important mechanism driving endothelial cell senescence. Thus, TSP1 and CD47 provide attractive molecular targets for treatment of aging-associated cardiovascular dysfunction and diseases involving endothelial dysregulation.
Atg5-dependent autophagy contributes to the development of acute myeloid leukemia in an MLL-AF9-driven mouse model
Authors: Liu Qiang , Chen Longgui , Atkinson Jennifer M , Claxton David F , Wang Hong-Gang
Published: September 2016

Acute myeloid leukemia (AML) is a hierarchical hematopoietic malignancy originating from leukemic stem cells (LSCs). Autophagy is a lysosomal degradation pathway that is hypothesized to be important for the maintenance of AML as well as contribute to chemotherapy response. Here we employ a mouse model of AML expressing the fusion oncogene MLL-AF9 and explore the effects of Atg5 deletion, a key autophagy protein, on the malignant transformation and progression of AML. Consistent with a transient decrease in colony-forming potential in vitro, the in vivo deletion of Atg5 in MLL-AF9-transduced bone marrow cells during primary transplantation prolonged the survival of recipient mice, suggesting that autophagy has a role in MLL-AF9-driven leukemia initiation. In contrast, deletion of Atg5 in malignant AML cells during secondary transplantation did not influence the survival or chemotherapeutic response of leukemic mice. Interestingly, autophagy was found to be involved in the survival of differentiated myeloid cells originating from MLL-AF9-driven LSCs. Taken together, our data suggest that Atg5-dependent autophagy may contribute to the development but not chemotherapy sensitivity of murine AML induced by MLL-AF9.
Rare variant phasing and haplotypic expression from RNA sequencing with phASER
Authors: Castel Stephane E. , Mohammadi Pejman , Chung Wendy K. , Shen Yufeng , Lappalainen Tuuli
Published: September 2016

Haplotype phasing of genetic variants is important for clinical interpretation of the genome, population genetic analysis and functional genomic analysis of allelic activity. Here we present phASER, an accurate approach for phasing variants that are overlapped by sequencing reads, including those from RNA sequencing (RNA-seq), which often span multiple exons due to splicing. Using diverse RNA-seq data we demonstrate that this provides more accurate phasing of rare variants compared with population-based phasing and allows phasing of variants in the same gene up to hundreds of kilobases away that cannot be obtained from DNA sequencing (DNA-seq) reads. We show that in the context of medical genetic studies this improves the resolution of compound heterozygotes. Additionally, phASER provides measures of haplotypic expression that increase power and accuracy in studies of allelic expression. In summary, phasing using RNA-seq and phASER is accurate and improves studies where rare variant haplotypes or allelic expression is needed.
Layer-specific cholinergic control of human and mouse cortical synaptic plasticity
Authors: Verhoog Matthijs B. , Obermayer Joshua , Kortleven Christian A. , Wilbers René , Wester Jordi , Baayen Johannes C. , De Kock Christiaan P. J. , Meredith Rhiannon M. , Mansvelder Huibert D.
Published: September 2016

Individual cortical layers have distinct roles in information processing. All layers receive cholinergic inputs from the basal forebrain (BF), which is crucial for cognition. Acetylcholinergic receptors are differentially distributed across cortical layers, and recent evidence suggests that different populations of BF cholinergic neurons may target specific prefrontal cortical (PFC) layers, raising the question of whether cholinergic control of the PFC is layer dependent. Here we address this issue and reveal dendritic mechanisms by which endogenous cholinergic modulation of synaptic plasticity is opposite in superficial and deep layers of both mouse and human neocortex. Our results show that in different cortical layers, spike timing-dependent plasticity is oppositely regulated by the activation of nicotinic acetylcholine receptors (nAChRs) either located on dendrites of principal neurons or on GABAergic interneurons. Thus, layer-specific nAChR expression allows functional layer-specific control of cortical processing and plasticity by the BF cholinergic system, which is evolutionarily conserved from mice to humans.
Integrating highly quantitative proteomics and genome-scale metabolic modeling to study pH adaptation in the human pathogen Enterococcus faecalis
Authors: Großeholz Ruth , Koh Ching-Chiek , Veith Nadine , Fiedler Tomas , Strauss Madlen , Olivier Brett , Collins Ben C , Schubert Olga T , Bergmann Frank , Kreikemeyer Bernd , Aebersold Ruedi , Kummer Ursula
Published: September 2016

Genome-scale metabolic models represent the entirety of metabolic reactions of an organism based on the annotation of the respective genome. These models commonly allow all reactions to proceed concurrently, disregarding the fact that at no point all proteins will be present in a cell. The metabolic reaction space can be constrained to a more physiological state using experimentally obtained information on enzyme abundances. However, high-quality, genome-wide protein measurements have been challenging and typically transcript abundances have been used as a surrogate for protein measurements. With recent developments in mass spectrometry-based proteomics, exemplified by SWATH-MS, the acquisition of highly quantitative proteome-wide data at reasonable throughput has come within reach. Here we present methodology to integrate such proteome-wide data into genome-scale models. We applied this methodology to study cellular changes in Enterococcus faecalis during adaptation to low pH. Our results indicate reduced proton production in the central metabolism and decreased membrane permeability for protons due to different membrane composition. We conclude that proteomic data constrain genome-scale models to a physiological state and, in return, genome-scale models are useful tools to contextualize proteomic data.
Enhancing Endosomal Escape for Intracellular Delivery of Macromolecular Biologic Therapeutics
Authors: Lönn Peter , Kacsinta Apollo D. , Cui Xian-Shu , Hamil Alexander S. , Kaulich Manuel , Gogoi Khirud , Dowdy Steven F.
Published: September 2016

Bioactive macromolecular peptides and oligonucleotides have significant therapeutic potential. However, due to their size, they have no ability to enter the cytoplasm of cells. Peptide/Protein transduction domains (PTDs), also called cell-penetrating peptides (CPPs), can promote uptake of macromolecules via endocytosis. However, overcoming the rate-limiting step of endosomal escape into the cytoplasm remains a major challenge. Hydrophobic amino acid R groups are known to play a vital role in viral escape from endosomes. Here we utilize a real-time, quantitative live cell split-GFP fluorescence complementation phenotypic assay to systematically analyze and optimize a series of synthetic endosomal escape domains (EEDs). By conjugating EEDs to a TAT-PTD/CPP spilt-GFP peptide complementation assay, we were able to quantitatively measure endosomal escape into the cytoplasm of live cells via restoration of GFP fluorescence by intracellular molecular complementation. We found that EEDs containing two aromatic indole rings or one indole ring and two aromatic phenyl groups at a fixed distance of six polyethylene glycol (PEG) units from the TAT-PTD-cargo significantly enhanced cytoplasmic delivery in the absence of cytotoxicity. EEDs address the critical rate-limiting step of endosomal escape in delivery of macromolecular biologic peptide, protein and siRNA therapeutics into cells.
Violet LED light enhances the recruitment of a thrip predator in open fields
Authors: Ogino Takumi , Uehara Takuya , Muraji Masahiko , Yamaguchi Terumi , Ichihashi Takahisa , Suzuki Takahiro , Kainoh Yooichi , Shimoda Masami
Published: September 2016

The predatory bug Orius sauteri is an indigenous natural enemy of thrips and whiteflies in Asian countries. To put these bugs to practical use in pest management, methods to attract and retain the bugs in agricultural fields are needed. We previously showed that violet light (405 nm) attracts O. sauteri selectively. Many thrips and whiteflies are attracted to UV or green light. In this study, we examined the effect of violet-LED illumination on O. sauteri in pesticide-free eggplant (Solanum melongena L.) cultivation. In three cultivation trials, the density of O. sauteri on eggplant leaves was consistently higher in the illuminated plots; at least twice that of the non-illuminated plots. Simultaneously, the density of thrips declined markedly to less than half that of the non-illuminated plots. We identified three positive effects of violet light including an “immediate-effect” on predator attraction, a “persistent-effect” on predator reproduction, and a “secondary-effect” on the food web structure. Our results showed that illumination with violet light provides a powerful tool for integrated pest management. This is the first report on the use of illumination to manipulate the behavior of natural enemies.
Allergens stimulate store-operated calcium entry and cytokine production in airway epithelial cells
Authors: Jairaman Amit , Maguire Chelsea H. , Schleimer Robert P. , Prakriya Murali
Published: September 2016

Aberrant immune responses to environmental allergens including insect allergens from house dust mites and cockroaches contribute to allergic inflammatory diseases such as asthma in susceptible individuals. Airway epithelial cells (AECs) play a critical role in this process by sensing the proteolytic activity of allergens via protease-activated receptors (PAR2) to initiate inflammatory and immune responses in the airway. Elevation of cytosolic Ca2+is an important signaling event in this process, yet the fundamental mechanism by which allergens induce Ca2+elevations in AECs remains poorly understood. Here we find that extracts from dust mite and cockroach induce sustained Ca2+elevations in AECs through the activation of Ca2+release-activated Ca2+(CRAC) channels encoded by Orai1 and STIM1. CRAC channel activation occurs, at least in part, through allergen mediated stimulation of PAR2 receptors. The ensuing Ca2+entry then activates NFAT/calcineurin signaling to induce transcriptional production of the proinflammatory cytokines IL-6 and IL-8. These findings highlight a key role for CRAC channels as regulators of allergen induced inflammatory responses in the airway.
Symmetry Breaking by Surface Blocking: Synthesis of Bimorphic Silver Nanoparticles, Nanoscale Fishes and Apples
Authors: Cathcart Nicole , Kitaev Vladimir
Published: September 2016

A powerful approach to augment the diversity of well-defined metal nanoparticle (MNP) morphologies, essential for MNP advanced applications, is symmetry breaking combined with seeded growth. Utilizing this approach enabled the formation of bimorphic silver nanoparticles (bi-AgNPs) consisting of two shapes linked by one regrowth point. Bi-AgNPs were formed by using an adsorbing polymer, poly(acrylic acid), PAA, to block the surface of a decahedral AgNP seed and restricting growth of new silver to a single nucleation point. First, we have realized 2-D growth of platelets attached to decahedra producing nanoscale shapes reminiscent of apples, fishes, mushrooms and kites. 1-D bimorphic growth of rods (with chloride) and 3-D bimorphic growth of cubes and bipyramids (with bromide) were achieved by using halides to induce preferential (100) stabilization over (111) of platelets. Furthermore, the universality of the formation of bimorphic nanoparticles was demonstrated by using different seeds. Bi-AgNPs exhibit strong SERS enhancement due to regular cavities at the necks. Overall, the reported approach to symmetry breaking and bimorphic nanoparticle growth offers a powerful methodology for nanoscale shape design.
Neuronal leucine-rich repeat 1 negatively regulates anaplastic lymphoma kinase in neuroblastoma
Authors: Satoh Shunpei , Takatori Atsushi , Ogura Atsushi , Kohashi Kenichi , Souzaki Ryota , Kinoshita Yoshiaki , Taguchi Tomoaki , Hossain Md. Shamim , Ohira Miki , Nakamura Yohko , Nakagawara Akira
Published: September 2016

In neuroblastoma (NB), one of the most common paediatric solid tumours, activation of anaplastic lymphoma kinase (ALK) is often associated with poor outcomes. Although genetic studies have identified copy number alteration and nonsynonymous mutations of ALK, the regulatory mechanism of ALK signalling at protein levels is largely elusive. Neuronal leucine-rich repeat 1 (NLRR1) is a type 1 transmembrane protein that is highly expressed in unfavourable NB and potentially influences receptor tyrosine kinase signalling. Here, we showed that NLRR1 and ALK exhibited a mutually exclusive expression pattern in primary NB tissues by immunohistochemistry. Moreover, dorsal root ganglia of Nlrr1+/+ and Nlrr1−/− mice displayed the opposite expression patterns of Nlrr1 and Alk. Of interest, NLRR1 physically interacted with ALK in vitro through its extracellular region. Notably, the NLRR1 ectodomain impaired ALK phosphorylation and proliferation of ALK-mutated NB cells. A newly identified cleavage of the NLRR1 ectodomain also supported NLRR1-mediated ALK signal regulation in trans. Thus, we conclude that NLRR1 appears to be an extracellular negative regulator of ALK signalling in NB and neuronal development. Our findings may be beneficial to comprehend NB heterogeneity and to develop a novel therapy against unfavourable NB.
Oscillatory brain activity during multisensory attention reflects activation, disinhibition, and cognitive control
Authors: Friese Uwe , Daume Jonathan , Göschl Florian , König Peter , Wang Peng , Engel Andreas K.
Published: September 2016

In this study, we used a novel multisensory attention paradigm to investigate attention-modulated cortical oscillations over a wide range of frequencies using magnetencephalography in healthy human participants. By employing a task that required the evaluation of the congruence of audio-visual stimuli, we promoted the formation of widespread cortical networks including early sensory cortices as well as regions associated with cognitive control. We found that attention led to increased high-frequency gamma-band activity and decreased lower frequency theta-, alpha-, and beta-band activity in early sensory cortex areas. Moreover, alpha-band coherence decreased in visual cortex. Frontal cortex was found to exert attentional control through increased low-frequency phase synchronisation. Crossmodal congruence modulated beta-band coherence in mid-cingulate and superior temporal cortex. Together, these results offer an integrative view on the concurrence of oscillations at different frequencies during multisensory attention.
Distinct roles of exogenous opioid agonists and endogenous opioid peptides in the peripheral control of neuropathy-triggered heat pain
Authors: Labuz Dominika , Celik Melih Ö. , Zimmer Andreas , Machelska Halina
Published: September 2016

Neuropathic pain often results from peripheral nerve damage, which can involve immune response. Local leukocyte-derived opioid peptides or exogenous opioid agonists inhibit neuropathy-induced mechanical hypersensitivity in animal models. Since neuropathic pain can also be augmented by heat, in this study we investigated the role of opioids in the modulation of neuropathy-evoked heat hypersensitivity. We used a chronic constriction injury of the sciatic nerve in wild-type and opioid peptide-knockout mice, and tested opioid effects in heat and mechanical hypersensitivity using Hargreaves and von Frey tests, respectively. We found that although perineural exogenous opioid agonists, including peptidergic ligands, were effective, the endogenous opioid peptides β-endorphin, Met-enkephalin and dynorphin A did not alleviate heat hypersensitivity. Specifically, corticotropin-releasing factor, an agent triggering opioid peptide secretion from leukocytes, applied perineurally did not attenuate heat hypersensitivity in wild-type mice. Exogenous opioids, also shown to release opioid peptides via activation of leukocyte opioid receptors, were equally analgesic in wild-type and opioid peptide-knockout mice, indicating that endogenous opioids do not contribute to exogenous opioid analgesia in heat hypersensitivity. Furthermore, exogenously applied opioid peptides were ineffective as well. Conversely, opioid peptides relieved mechanical hypersensitivity. Thus, both opioid type and sensory modality may determine the outcome of neuropathic pain treatment.
A Closed Loop Brain-machine Interface for Epilepsy Control Using Dorsal Column Electrical Stimulation
Authors: Pais-Vieira Miguel , Yadav Amol P. , Moreira Derek , Guggenmos David , Santos Amílcar , Lebedev Mikhail , Nicolelis Miguel A. L.
Published: September 2016

Although electrical neurostimulation has been proposed as an alternative treatment for drug-resistant cases of epilepsy, current procedures such as deep brain stimulation, vagus, and trigeminal nerve stimulation are effective only in a fraction of the patients. Here we demonstrate a closed loop brain-machine interface that delivers electrical stimulation to the dorsal column (DCS) of the spinal cord to suppress epileptic seizures. Rats were implanted with cortical recording microelectrodes and spinal cord stimulating electrodes, and then injected with pentylenetetrazole to induce seizures. Seizures were detected in real time from cortical local field potentials, after which DCS was applied. This method decreased seizure episode frequency by 44% and seizure duration by 38%. We argue that the therapeutic effect of DCS is related to modulation of cortical theta waves, and propose that this closed-loop interface has the potential to become an effective and semi-invasive treatment for refractory epilepsy and other neurological disorders.
Transcriptomic profiling of long non-coding RNAs in dermatomyositis by microarray analysis
Authors: Peng Qing-Lin , Zhang Ya-Mei , Yang Han-Bo , Shu Xiao-Ming , Lu Xin , Wang Guo-Chun
Published: September 2016

Long non-coding RNAs (lncRNAs) are prevalently transcribed in the genome and have been found to be of functional importance. However, the potential roles of lncRNAs in dermatomyositis (DM) remain unknown. In this study, a lncRNA + mRNA microarray analysis was performed to profile lncRNAs and mRNAs from 15 treatment-naive DM patients and 5 healthy controls. We revealed a total of 1198 lncRNAs (322 up-regulated and 876 down-regulated) and 1213 mRNAs (665 up-regulated and 548 down-regulated) were significantly differentially expressed in DM patients compared with the healthy controls (fold change>2, P < 0.05). Subgrouping DM patients according to the presence of interstitial lung disease and anti-Jo-1 antibody revealed different expression patterns of the lncRNAs. Pathway and gene ontology analysis for the differentially expressed mRNAs confirmed that type 1 interferon signaling was the most significantly dysregulated pathway in all DM subgroups. In addition, distinct pathways that uniquely associated with DM subgroup were also identified. Bioinformatics prediction suggested that linc-DGCR6-1 may be a lncRNA that regulates type 1 interferon-inducible gene USP18, which was found highly expressed in the perifascicular areas of the muscle fibers of DM patients. Our findings provide an overview of aberrantly expressed lncRNAs in DM muscle and further broaden the understanding of DM pathogenesis.
Magnetic Yoking and Tunable Interactions in FePt-Based Hard/Soft Bilayers
Authors: Gilbert Dustin A. , Liao Jung-Wei , Kirby Brian J. , Winklhofer Michael , Lai Chih-Huang , Liu Kai
Published: September 2016

Magnetic interactions in magnetic nanostructures are critical to nanomagnetic and spintronic explorations. Here we demonstrate an extremely sensitive magnetic yoking effect and tunable interactions in FePt based hard/soft bilayers mediated by the soft layer. Below the exchange length, a thin soft layer strongly exchange couples to the perpendicular moments of the hard layer; above the exchange length, just a few nanometers thicker, the soft layer moments turn in-plane and act to yoke the dipolar fields from the adjacent hard layer perpendicular domains. The evolution from exchange to dipolar-dominated interactions is experimentally captured by first-order reversal curves, the ΔM method, and polarized neutron reflectometry, and confirmed by micromagnetic simulations. These findings demonstrate an effective yoking approach to design and control magnetic interactions in wide varieties of magnetic nanostructures and devices.
Discovery of Fe7O9: a new iron oxide with a complex monoclinic structure
Authors: Sinmyo Ryosuke , Bykova Elena , Ovsyannikov Sergey V. , McCammon Catherine , Kupenko Ilya , Ismailova Leyla , Dubrovinsky Leonid
Published: September 2016

Iron oxides are fundamentally important compounds for basic and applied sciences as well as in numerous industrial applications. In this work we report the synthesis and investigation of a new binary iron oxide with the hitherto unknown stoichiometry of Fe7O9. This new oxide was synthesized at high-pressure high-temperature (HP-HT) conditions, and its black single crystals were successfully recovered at ambient conditions. By means of single crystal X-ray diffraction we determined that Fe7O9 adopts a monoclinic C2/m lattice with the most distorted crystal structure among the binary iron oxides known to date. The synthesis of Fe7O9 opens a new portal to exotic iron-rich (M,Fe)7O9 oxides with unusual stoichiometry and distorted crystal structures. Moreover, the crystal structure and phase relations of such new iron oxide groups may provide new insight into the cycling of volatiles in the Earth’s interior.
A magneto-DNA nanoparticle system for the rapid and sensitive diagnosis of enteric fever
Authors: Park Ki Soo , Chung Hyun Jung , Khanam Farhana , Lee Hakho , Rashu Rasheduzzaman , Bhuiyan Md. Taufiqur , Berger Amanda , Harris Jason B. , Calderwood Stephen B. , Ryan Edward T. , Qadri Firdausi , Weissleder Ralph , Charles Richelle C.
Published: September 2016

There is currently no widely available optimal assay for diagnosing patients with enteric fever. Here we present a novel assay designed to detect amplified Salmonella nucleic acid (mRNA) using magneto-DNA probes and a miniaturized nuclear magnetic resonance device. We designed primers for genes specific to S. Typhi, S. Paratyphi A, and genes conserved among Salmonella enterica spp. and utilized strongly magnetized nanoparticles to enhance the detection signal. Blood samples spiked with in vitro grown S. Typhi, S. Paratyphi A, S. Typhimurium, and E. coli were used to confirm the specificity of each probe-set, and serial 10-fold dilutions were used to determine the limit of the detection of the assay, 0.01–1.0 CFU/ml. For proof of principle, we applied our assay to 0.5 mL blood samples from 5 patients with culture-confirmed enteric fever from Bangladesh in comparison to 3 healthy controls. We were able to detect amplified target cDNA in all 5 cases of enteric fever; no detectable signal was seen in the healthy controls. Our results suggest that a magneto-DNA nanoparticle system, with an assay time from blood collection of 3.5 hours, may be a promising platform for the rapid and culture-free diagnosis of enteric fever and non-typhoidal Salmonella bacteremia.
Restriction of Aerobic Metabolism by Acquired or Innate Arylsulfatase B Deficiency: A New Approach to the Warburg Effect
Authors: Bhattacharyya Sumit , Feferman Leo , Tobacman Joanne K.
Published: September 2016

Aerobic respiration is required for optimal efficiency of metabolism in mammalian cells. Under circumstances when oxygen utilization is impaired, cells survive by anerobic metabolism. The malignant cell has cultivated the use of anerobic metabolism in an aerobic environment, the Warburg effect, but the explanation for this preference is not clear. This paper presents evidence that deficiency of the enzyme arylsulfatase B (ARSB; N-acetylgalactosamine 4-sulfatase), either innate or acquired, helps to explain the Warburg phenomenon. ARSB is the enzyme that removes 4-sulfate groups from the non-reducing end of chondroitin 4-sulfate and dermatan sulfate. Previous reports indicated reduced ARSB activity in malignancy and replication of the effects of hypoxia by decline in ARSB. Hypoxia reduced ARSB activity, since molecular oxygen is needed for post-translational modification of ARSB. In this report, studies were performed in human HepG2 cells and in hepatocytes from ARSB-deficient and normal C57BL/6J control mice. Decline of ARSB, in the presence of oxygen, profoundly reduced the oxygen consumption rate and increased the extracellular acidification rate, indicating preference for aerobic glycolysis. Specific study findings indicate that decline in ARSB activity enhanced aerobic glycolysis and impaired normal redox processes, consistent with a critical role of ARSB and sulfate reduction in mammalian metabolism.
Fast set-based association analysis using summary data from GWAS identifies novel gene loci for human complex traits
Authors: Bakshi Andrew , Zhu Zhihong , Vinkhuyzen Anna A. E. , Hill W. David , McRae Allan F. , Visscher Peter M. , Yang Jian
Published: September 2016

We propose a method (fastBAT) that performs a fast set-based association analysis for human complex traits using summary-level data from genome-wide association studies (GWAS) and linkage disequilibrium (LD) data from a reference sample with individual-level genotypes. We demonstrate using simulations and analyses of real datasets that fastBAT is more accurate and orders of magnitude faster than the prevailing methods. Using fastBAT, we analyze summary data from the latest meta-analyses of GWAS on 150,064–339,224 individuals for height, body mass index (BMI), and schizophrenia. We identify 6 novel gene loci for height, 2 for BMI, and 3 for schizophrenia at PfastBAT < 5 × 10−8. The gain of power is due to multiple small independent association signals at these loci (e.g. the THRB and FOXP1 loci for schizophrenia). The method is general and can be applied to GWAS data for all complex traits and diseases in humans and to such data in other species.
Erratum: Context-dependent dynamic UV signaling in female threespine sticklebacks
Authors: Hiermes Meike , Bakker Theo C. M. , Mehlis Marion , Rick Ingolf P.
Published: September 2016

Scientific Reports 5: Article number: 17474; published online: 10 December 2015; updated: 08 September 2016
Role of coherence and delocalization in photo-induced electron transfer at organic interfaces
Authors: Abramavicius V. , Pranculis V. , Melianas A. , Inganäs O. , Gulbinas V. , Abramavicius D.
Published: September 2016

Photo-induced charge transfer at molecular heterojunctions has gained particular interest due to the development of organic solar cells (OSC) based on blends of electron donating and accepting materials. While charge transfer between donor and acceptor molecules can be described by Marcus theory, additional carrier delocalization and coherent propagation might play the dominant role. Here, we describe ultrafast charge separation at the interface of a conjugated polymer and an aggregate of the fullerene derivative PCBM using the stochastic Schrödinger equation (SSE) and reveal the complex time evolution of electron transfer, mediated by electronic coherence and delocalization. By fitting the model to ultrafast charge separation experiments, we estimate the extent of electron delocalization and establish the transition from coherent electron propagation to incoherent hopping. Our results indicate that even a relatively weak coupling between PCBM molecules is sufficient to facilitate electron delocalization and efficient charge separation at organic interfaces.
Involvement of type VI secretion system in secretion of iron chelator pyoverdine in Pseudomonas taiwanensis
Authors: Chen Wen-Jen , Kuo Tzu-Yen , Hsieh Feng-Chia , Chen Pi-Yu , Wang Chang-Sheng , Shih Yu-Ling , Lai Ying-Mi , Liu Je-Ruei , Yang Yu-Liang , Shih Ming-Che
Published: September 2016

Rice bacterial blight caused by Xanthomonas oryzae pv. oryzae (Xoo) is one of the most destructive rice diseases worldwide. Therefore, in addition to breeding disease-resistant rice cultivars, it is desirable to develop effective biocontrol agents against Xoo. Here, we report that a soil bacterium Pseudomonas taiwanensis displayed strong antagonistic activity against Xoo. Using matrix-assisted laser desorption/ionization imaging mass spectrometry, we identified an iron chelator, pyoverdine, secreted by P. taiwanensis that could inhibit the growth of Xoo. Through Tn5 mutagenesis of P. taiwanensis, we showed that mutations in genes that encode components of the type VI secretion system (T6SS) as well as biosynthesis and maturation of pyoverdine resulted in reduced toxicity against Xoo. Our results indicated that T6SS is involved in the secretion of endogenous pyoverdine. Mutations in T6SS component genes affected the secretion of mature pyoverdine from the periplasmic space into the extracellular medium after pyoverdine precursor is transferred to the periplasm by the inner membrane transporter PvdE. In addition, we also showed that other export systems, i.e., the PvdRT-OpmQ and MexAB-OprM efflux systems (for which there have been previous suggestions of involvement) and the type II secretion system (T2SS), are not involved in pyoverdine secretion.
NSD2 contributes to oncogenic RAS-driven transcription in lung cancer cells through long-range epigenetic activation
Authors: García-Carpizo Verónica , Sarmentero Jacinto , Han Bomie , Graña Osvaldo , Ruiz-Llorente Sergio , Pisano David G. , Serrano Manuel , Brooks Harold B. , Campbell Robert M. , Barrero Maria J.
Published: September 2016

The histone methyltransferase NSD2/WHSC1/MMSET is overexpressed in a number of solid tumors but its contribution to the biology of these tumors is not well understood. Here, we describe that NSD2 contributes to the proliferation of a subset of lung cancer cell lines by supporting oncogenic RAS transcriptional responses. NSD2 knock down combined with MEK or BRD4 inhibitors causes co-operative inhibitory responses on cell growth. However, while MEK and BRD4 inhibitors converge in the downregulation of genes associated with cancer-acquired super-enhancers, NSD2 inhibition affects the expression of clusters of genes embedded in megabase-scale regions marked with H3K36me2 and that contribute to the RAS transcription program. Thus, combinatorial therapies using MEK or BRD4 inhibitors together with NSD2 inhibition are likely to be needed to ensure a more comprehensive inhibition of oncogenic RAS-driven transcription programs in lung cancers with NSD2 overexpression.
Nanoionics and Nanocatalysts: Conformal Mesoporous Surface Scaffold for Cathode of Solid Oxide Fuel Cells
Authors: Chen Yun , Gerdes Kirk , Song Xueyan
Published: September 2016

Nanoionics has become increasingly important in devices and systems related to energy conversion and storage. Nevertheless, nanoionics and nanostructured electrodes development has been challenging for solid oxide fuel cells (SOFCs) owing to many reasons including poor stability of the nanocrystals during fabrication of SOFCs at elevated temperatures. In this study, a conformal mesoporous ZrO2 nanoionic network was formed on the surface of La1−xSrxMnO3/yttria-stabilized zirconia (LSM/YSZ) cathode backbone using Atomic Layer Deposition (ALD) and thermal treatment. The surface layer nanoionic network possesses open mesopores for gas penetration, and features a high density of grain boundaries for enhanced ion-transport. The mesoporous nanoionic network is remarkably stable and retains the same morphology after electrochemical operation at high temperatures of 650–800 °C for 400 hours. The stable mesoporous ZrO2 nanoionic network is further utilized to anchor catalytic Pt nanocrystals and create a nanocomposite that is stable at elevated temperatures. The power density of the ALD modified and inherently functional commercial cells exhibited enhancement by a factor of 1.5–1.7 operated at 0.8 V at 750 °C.
Recent Trends of Summer Convective and Stratiform Precipitation in Mid-Eastern China
Authors: Fu Yunfei , Chen Fengjiao , Liu Guosheng , Yang Yuanjian , Yuan Renmin , Li Rui , Liu Qi , Wang Yu , Zhong Lei , Sun Liang
Published: September 2016

Many studies have reported on the trends of precipitation in Mid-Eastern China (EC). However, the trends of convective and stratiform precipitation are still unknown. Here, we examine the trends of summer convective and stratiform precipitation in EC from 2002 to 2012 on the basis of the TRMM observations. Results revealed that the rain frequency (RF) for both convective and stratiform precipitation increased in majority regions of Southern EC (SEC), but decreased in Northwest part of Northern EC (NEC). The decreasing rate of RF for stratiform precipitation in NEC is twice as much as that for convective precipitation, while the increase of convective precipitation in SEC is more evident than stratiform precipitation. The rain rate (RR) exhibited a decreasing trend in most portions of EC for both convective and stratiform precipitation. In SEC, neither PW nor WVT has good ability in explaining the precipitation variability. However, in NEC, PW is closely correlated to convective RF and WVT is more closely related to stratiform RF.
Acoustic structure quantification by using ultrasound Nakagami imaging for assessing liver fibrosis
Authors: Tsui Po-Hsiang , Ho Ming-Chih , Tai Dar-In , Lin Ying-Hsiu , Wang Chiao-Yin , Ma Hsiang-Yang
Published: September 2016

Acoustic structure quantification (ASQ) is a recently developed technique widely used for detecting liver fibrosis. Ultrasound Nakagami parametric imaging based on the Nakagami distribution has been widely used to model echo amplitude distribution for tissue characterization. We explored the feasibility of using ultrasound Nakagami imaging as a model-based ASQ technique for assessing liver fibrosis. Standard ultrasound examinations were performed on 19 healthy volunteers and 91 patients with chronic hepatitis B and C (n = 110). Liver biopsy and ultrasound Nakagami imaging analysis were conducted to compare the METAVIR score and Nakagami parameter. The diagnostic value of ultrasound Nakagami imaging was evaluated using receiver operating characteristic (ROC) curves. The Nakagami parameter obtained through ultrasound Nakagami imaging decreased with an increase in the METAVIR score (p < 0.0001), representing an increase in the extent of pre-Rayleigh statistics for echo amplitude distribution. The area under the ROC curve (AUROC) was 0.88 for the diagnosis of any degree of fibrosis (≥F1), whereas it was 0.84, 0.69, and 0.67 for ≥F2, ≥F3, and ≥F4, respectively. Ultrasound Nakagami imaging is a model-based ASQ technique that can be beneficial for the clinical diagnosis of early liver fibrosis.
Comparative efficacy and safety of urate-lowering therapy for the treatment of hyperuricemia: a systematic review and network meta-analysis
Authors: Li Shu , Yang Hongxi , Guo Yanan , Wei Fengjiang , Yang Xilin , Li Daiqing , Li Mingzhen , Xu Weili , Li Weidong , Sun Li , Gao Ying , Wang Yaogang
Published: September 2016

The prevalence of hyperuricemia and gout has been increasing, but the comparative effectiveness and safety of different treatments remain uncertain. We aimed to compare the effectiveness and safety of different treatments for hyperuricemia using network meta-analysis methodology. We systematically reviewed fifteen randomized controlled trials (involving 7,246 patients through January 2016) that compared the effects of different urate-lowering drugs (allopurinol, benzbromarone, febuxostat, pegloticase and probenecid) on hyperuricemia. Drug efficacy and safety, as outcomes, were measured by whether the target level of serum urate acid was achieved and whether any adverse events occurred, respectively. We derived pooled effect sizes expressed as odds ratios (ORs) and 95% confidence intervals (CIs). The efficacy and safety of the drugs were ranked by cumulative ranking probabilities. Our findings show that febuxostat, benzbromarone, probenecid, pegloticase, and allopurinol were all highly effective at reducing the risk of hyperuricemia compared to placebo. Febuxostat had the best efficacy and safety compared to the other drugs. Furthermore, febuxostat 120 mg QD was more effective at achieving urate-lowering targets (OR: 0.17, 95% CI: 0.12–0.24) and safer (OR: 0.72, 95% CI: 0.56–0.91) than allopurinol.