bluuebunny/crossref_metadata_2025 huggingface dataset:
Modified harmonic minimisation technique for doubly fed induction generators with solar‐wind hybrid system using biogeography‐based optimisation
Authors: Sarker Krishna , Chatterjee Debashis , Goswami Swapan K.
Published: March 2018

This study develops a framework for optimisation of rotor side converter (RSC) switching to eliminate lower‐order harmonic injection of a doubly fed induction generator connected to a grid. A biogeography based optimisation (BBO) technique is used for this purpose. Three level inverters operating in either 120° or 180° modes at slip frequency are usually employed for the RSC to reduce switching losses. Non‐sinusoidal rotor injected voltages by RSC generates undesirable stator harmonics based on the operating rotor speed. Induced harmonics in the stator are analysed and computed. A modified switching strategy is developed to reduce stator harmonics at different speeds. A BBO‐based technique is used to compute the switching angles off‐line controlled with minimum injected harmonics at closed intervals of modulation indices. These angles are stored in processor memory for an on‐line application using mixed model equations which have low memory usage. Various simulations are executed and supported by suitable experiments with a practical machine for verification of the proposed model which provided satisfactory results.
Abundance of HCN and its C and N isotopologues in L1498
Authors: Magalhães V. S. , Hily-Blant P. , Faure A. , Hernandez-Vera M. , Lique F.
Published: March 2018

The isotopic ratio of nitrogen in nearby protoplanetary disks, recently measured in CN and HCN, indicates that a fractionated reservoir of volatile nitrogen is available at the earliest stage of comet formation. This reservoir also presents a 3:1 enrichment in 15N relative to the elemental ratio of 330, identical to that between the solar system comets and the protosun, suggesting that similar processes are responsible for the fractionation in the protosolar nebula (PSN) and in these PSN analogs. However, where, when, and how the fractionation of nitrogen takes place is an open question. Previously obtained HCN/HC15N abundance ratios suggest that HCN may already be enriched in 15N in prestellar cores, although doubts remain on these measurements, which rely on the double-isotopologue method. Here we present direct measurements of the HCN/H13CN and HCN/HC15N abundance ratios in the L1498 prestellar core based on spatially resolved spectra of HCN(1–0), (3–2), H13CN(1–0), and HC15N(1–0) rotational lines. We use state-of-the-art radiative transfer calculations using ALICO, a 1D radiative transfer code capable of treating hyperfine overlaps. From a multiwavelength analysis of dust emission maps of L1498, we derive a new physical structure of the L1498 cloud. We also use new, high-accuracy HCN-H2 hyperfine collisional rates, which enable us to quantitatively reproduce all the features seen in the line profiles of HCN(1–0) and HCN(3–2), especially the anomalous hyperfine line ratios. Special attention is devoted to derive meaningful uncertainties on the abundance ratios. The obtained values, HCN/H13CN = 45 ± 3 and HCN/HC15N = 338 ± 28, indicate that carbon is heavily fractionated in HCN, but nitrogen is not. For the H13CN/HC15N abundance ratio, our detailed study validates to some extent analyses based on the single excitation temperature assumption. Comparisons with other measurements from the literature suggest significant core-to-core variability. Furthermore, the heavy 13C enrichment we found in HCN could explain the superfractionation of nitrogen measured in solar system chondrites.
Critical Elements in Fly Ash from the Combustion of Bituminous Coal in Major Polish Power Plants
Authors: Bielowicz Barbara , Botor Dariusz , Misiak Jacek , Wagner Marian
Published: March 2018

The concentration of critical elements, including such REE as Fe, Co, W, Zn, Cr, Ni, V, Mn, Ti, Ag, Ga, Ta, Sr, Li, and Cu, in the so-called fly ash obtained from the 9 Polish power plants and 1 thermal power station has been determined. The obtained values, compared with the global average concentration in bituminous coal ash and sedimentary rocks (Clarke values), have shown that the enrichment of fly ash in the specified elements takes place in only a few bituminous coal processing sites in Poland. The enrichment factor (EF) is only slightly higher (the same order of magnitude) than the Clarke values. The enrichment factor in relation to the Clarke value in the Earth’s crust reached values above 10 in all of the examined ashes for the following elements: Cr, Ni, V, W, and, in some ash samples, also Cu and Zn. The obtained values are low, only slightly higher than the global average concentrations in sedimentary rocks and bituminous coal ashes. The ferromagnetic grains (microspheres) found in bituminous coal fly ashes seem to be the most economically prospective in recovery of selected critical elements. The microanalysis has shown that iron cenospheres and plerospheres in fly ash contain, in addition to enamel and iron oxides (magnetite and hematite), iron spinels enriched in Co, Cr, Cu, Mn, Ni, W, and Zn.
Experience in the Education of Engineers from Vietnam in the Faculty of Mining and Geoengineering AGH
Authors: Cała Marek , Borowski Marek
Published: March 2018

The AGH University of Science and Technology collaborates closely with other universities, economic units, governmental and local administrative bodies. International cooperation plays a very important role in the academic research. The AGH University of Science and Technology has signed many collaboration agreements. They aim at multidimensional cooperation in the fields of education and academic research. AGH UST has always focused on collaboration with business and industry. In recent years, the global economy is undergoing massive transformations, what creates new challenges to companies and educational institutions that cater to the needs of industry. The expansion of business enterprises is largely dependent on their employees’ expertise, skills and levels of competence. Certified engineers are provided by universities. Therefore, the qualifications of the graduates are determined by the curriculum and teaching methods, as well as the available educational and research facilities. Of equal importance is the qualified academic staff. Human activities in the field of engineering require finding solutions to problems of various nature and magnitude. An engineer’s work consists in the design, construction, modification and maintenance of useful devices, processes and systems, using scientific and technical knowledge. In order to design complex engineering solutions, an engineer uses his imagination, experience, analytical skills, logical reasoning and makes conscious use of his knowledge. At the Faculty of Mining and Geoengineering of the AGH University of Science and Technology in Cracow, 15 engineers from Vietnam are studying Mining and Geology at the second-cycle studies (specialization: mine ventilation). The solutions proposed in the field of the engineers’ education guarantee that foreign students gain both engineering knowledge and problem-solving skills. Therefore, the study programme was complemented by a series of practical aspects.
Ich würde dich so gerne verstehen!
Authors: Bär Marion
Published: March 2018

Hermeneutische Kompetenz in der Pflege von Menschen mit Demenz Bei der Pflege von Menschen mit Demenz kommen Pflegende immer wieder an ihre Grenzen.
Hilfreich ist, die eigene Haltung zu überprüfen und den Blickwinkel zu ändern. Unsere Autorin erläutert anhand eines Fallbeispiels, wie die Schlüsselkompetenz
„Verstehen“ trainiert werden kann und bedürfnisorientierte Pflege gelingt.
Tourism demand modelling and forecasting.
Authors: Witt S. F. , Moutinho L. , Huarng KunHuang Huarng KunHuang , Yu HuiKuang [Yu H. K. T. ]
Published: March 2018

This chapter examines several tourism demand forecasting methods (qualitative and quantitative) and provides examples which illustrate potential applications of the various methods. The main methods described are: Delphi and jury of executive opinion; cross-impact analysis; probability forecasting; econometric forecasting; and fuzzy time series forecasting.
Strategic thinking in tourism.
Authors: Vargas-Sánchez A. , Moutinho L.
Published: March 2018

This chapter introduces the nascent issue of strategic thinking in tourism. There is an initial section on the meaning of management. The chapter then delves into the changing fortunes of strategic planning as well as into the underpinnings of systems thinking. Sense and respond systems, strategic agility and value-based management are also covered. The chapter ends with the introduction of a novel concept: betapreneurship.
Authenticity in tourism.
Authors: Reisinger Y.
Published: March 2018

This chapter discusses the concept of authenticity that can be produced or pursued through tourism activities. The main types of authenticity and their meanings in tourism are discussed, as well as the critiques of the concept and the challenges it presents to tourism professionals. Strategies for achieving and communicating authenticity are outlined, and the implications for managing authenticity in tourism are discussed.
Higher susceptibility to osmolality of the medaka (Oryzias latipes) mutants in orthologue genes of mammalian skin transglutaminases
Authors: Watanabe Yuko , Furukawa Eri , Tatsukawa Hideki , Hashimoto Hisashi , Kamei Yasuhiro , Taniguchi Yoshihito , Hitomi Kiyotaka
Published: March 2018

Transglutaminase (TG) is an essential enzyme to catalyze cross-linking reactions of epidermal proteins. Recently, we biochemically characterized human skin TG orthologues for medaka (Oryzias latipes), a model fish. By genome editing, gene-modified fishes for the two orthologues were obtained, both of which lack the ordinal enzymes. These fish appeared to exhibit higher susceptibility to osmolality at the period of larvae.
Application of Improved Grey Model in Medium and Long Term Load Forecasting
Authors: Che Xuan
Published: March 2018

Grey model is a common method in medium and long-term power load forecasting, but it has great limitations. According to the characteristics of medium and long term power load forecasting, the method of sliding average and the principle of Markov model are introduced into the Grey forecasting theory, and the model is improved. This improvement can effectively improve the prediction accuracy of the model. Based on the load data of Qingdao City in the past ten years, it can be proved that the improved Grey model has improved the accuracy of the former.
All the World Loves a Lover: Monarchy, Mass Media and the 1934 Royal Wedding of Prince George and Princess Marina
Authors: Owens Edward
Published: March 2018

This essay examines the little-studied 1934 royal wedding of Prince George, Duke of Kent, the youngest surviving son of George V and the famously glamorous Princess Marina of Greece to argue that the British media projected this event on a scale, and in ways, never seen before. More than on any previous occasion it was a royal event driven by intimate publicity, and by a coterie of courtiers, clerics and newsmen who were committed to elevating a ‘family monarchy’ as the emotional centre-point of national life. I suggest that this celebration of royal domesticity engendered popular support for the House of Windsor in a period characterised by political turbulence at home and abroad. In this vein, I argue that social elites orchestrated royal family events as mass mediated nation-building exercises designed to create loyal subjects to the Crown, and that new technologies transformed how media audiences and royalty interacted with one another.
Increases in Neuroticism May Be an Early Indicator of Dementia: A Coordinated Analysis
Authors: Yoneda Tomiko , Rush Jonathan , Graham Eileen K , Berg Anne Ingeborg , Comijs Hannie , Katz Mindy , Lipton Richard B , Johansson Boo , Mroczek Daniel K , Piccinin Andrea M
Published: March 2018

Objectives

Although personality change is typically considered a symptom of dementia, some studies suggest that personality change may be an early indication of dementia. One prospective study found increases in neuroticism preceding dementia diagnosis (Yoneda, T., Rush, J., Berg, A. I., Johansson, B., & Piccinin, A. M. (2017). Trajectories of personality traits preceding dementia diagnosis. The Journals of Gerontology. Series B, Psychological Sciences and Social Sciences, 72, 922–931. doi:10.1093/geronb/gbw006). This study extends this research by examining trajectories of personality traits in additional longitudinal studies of aging.

Methods

Three independent series of latent growth curve models were fitted to data from the Longitudinal Aging Study Amsterdam and Einstein Aging Study to estimate trajectories of personality traits in individuals with incident dementia diagnosis (total N = 210), in individuals with incident Mild Cognitive Impairment (N = 135), and in individuals who did not receive a diagnosis during follow-up periods (total N = 1740).

Results

Controlling for sex, age, education, depressive symptoms, and the interaction between age and education, growth curve analyses consistently revealed significant linear increases in neuroticism preceding dementia diagnosis in both datasets and in individuals with mild cognitive impairment. Analyses examining individuals without a diagnosis revealed nonsignificant change in neuroticism overtime.

Discussion

Replication of our previous work in 2 additional datasets provides compelling evidence that increases in neuroticism may be early indication of dementia, which can facilitate development of screening assessments.
Re-experiencing Violence Across the Life Course: Histories of Childhood Maltreatment and Elder Abuse Victimization
Authors: Kong Jooyoung , Easton Scott D
Published: March 2018

Objectives

This study primarily examines the associations between histories of childhood maltreatment (i.e., neglect, emotional, physical, and sexual abuse) and elder abuse victimization and explores whether gender moderates the associations.

Methods

We conducted a secondary data analysis of 5,968 older adults (mean age = 71 years) based on data from the Wisconsin Longitudinal Study (2010–2011). Using retrospective self-reports of childhood and current (past 12 months) victimization experiences, logistic regression analyses were conducted to estimate the effects of early-life adversities on the likelihood of elder abuse victimization.

Results

Results indicate that childhood emotional abuse and childhood sexual abuse (CSA) were associated with greater risk of being abused as older adults, after controlling for childhood and adult background factors. We also found that the effect of CSA on elder abuse victimization was weaker for women than men.

Discussion

Findings suggest that the phenomenon of revictimization may occur not only in early and middle adulthood, but also in late life. To advance our understanding of victimization across the life course, future research on root causes of elder abuse should include histories of child abuse.
ε-Regularity and Structure of Four-dimensional Shrinking Ricci Solitons
Authors: Huang Shaosai
Published: March 2018

A closed four-dimensional manifold cannot possess a non-flat Ricci soliton metric with arbitrarily small $L^{2}$-norm of the curvature. In this paper, we localize this fact in the case of gradient shrinking Ricci solitons by proving an $\varepsilon $-regularity theorem, thus confirming a conjecture of Cheeger–Tian [20]. As applications, we will also derive structural results concerning the degeneration of the metrics on a family of complete non-compact four-dimensional gradient shrinking Ricci solitons without a uniform entropy lower bound. In the appendix, we provide a detailed account of the equivariant good chopping theorem when collapsing with locally bounded curvature happens.
A Cross-sectional Surveillance Study of the Frequency and Etiology of Acute Respiratory Illness Among Pregnant Women
Authors: Hause Anne M , Avadhanula Vasanthi , Maccato Maurizio L , Pinell Phillip M , Bond Nanette , Santarcangelo Patricia , Ferlic-Stark Laura , Munoz Flor M , Piedra Pedro A
Published: March 2018

Background

Other than influenza, little is known about the consequences of viral acute respiratory illness (ARI) on pregnant women and fetuses. Our objectives were to determine the frequency of ARI due to respiratory viruses and the associated clinical outcomes during pregnancy.

Methods

Pregnant women in their second or third trimester were enrolled if they reported having symptoms of ARI or were healthy within the preceding 2 weeks. Nasopharyngeal secretions were evaluated for respiratory viruses by molecular diagnostic assays. Clinical outcomes were evaluated at enrollment and via a follow-up telephone-based questionnaire 2 weeks later.

Results

There were 155 pregnant participants, with 81 ARI cases and 91 healthy controls. Acute lower respiratory tract illness (ALRTI) was identified in 29 cases (36%). Human rhinovirus (HRV), respiratory syncytial virus (RSV), and influenza virus accounted for 75% of virus-positive cases of ALRTI. Cases with ALRTI often reported a longer duration of illness, history of allergies, symptoms of wheezing, shortness of breath, or chest pain, and use of prescription medication. Two cases with ALRTI reported decreased fetal movement; a third case with ALRTI was hospitalized.

Conclusions

In over one third of ARI cases, participants had symptoms consistent with ALRTI. Infection with HRV, RSV, or influenza virus was commonly detected in patients with ALRTI. Viral ALRTI during pregnancy appears to be common and is associated with significant morbidity.
Multifrequency behaviour of the anomalous events of PSR J0922+0638
Authors: Shaifullah G , Tiburzi C , Osłowski S , Verbiest J P W , Szary A , Künsemöller J , Horneffer A , Anderson J , Kramer M , Schwarz D J , Mann G , Steinmetz M , Vocks C
Published: March 2018

PSR J0922+0638 (B0919+06) shows unexplained anomalous variations in the on-pulse phase, where the pulse appears to episodically move to an earlier longitude for a few tens of rotations before reverting to the usual phase for approximately several hundred to more than a thousand rotations. These events, where the pulse moves in phase by up to 5°, have been previously detected in observations from ∼300 to 2000 MHz. We present simultaneous observations from the Effelsberg 100-m radio telescope at 1350 MHz and the Bornim (Potsdam) station of the LOw Frequency ARray at 150 MHz. Our observations present the first evidence for an absence of the anomalous phase-shifting behaviour at 150 MHz. Instead, the observed intensity at the usual pulse-phase typically decreases, often showing a pseudo-nulling feature corresponding to the times when phase shifts are observed at 1350 MHz. The presence of weak emission at the usual pulse-phase supports the theory that these shifts may result from processes similar to the ‘profile-absorption’ expected to operate for PSR J0814+7429 (B0809+74). A possible mechanism for this could be intrinsic variations of the emission within the pulsar’s beam combined with absorption by expanding shells of electrons in the line of sight.
Can the relativistic light-bending model explain X-ray spectral variations of Seyfert galaxies?
Authors: Mizumoto Misaki , Moriyama Kotaro , Ebisawa Ken , Mineshige Shin , Kawanaka Norita , Tsujimoto Masahiro
Published: March 2018

Many Seyfert galaxies are known to exhibit Fe-K broad emission line features in their X-ray energy spectra. The observed lines have three distinct features: (1) the line profiles are skewed and show significant low-energy tails, (2) the Fe-K band has low variability, which produces a broad and deep dip in the root-mean-square (rms) spectra, and (3) photons in this band have time lags behind those in the adjacent energy bands with amplitudes of several Rg/c, where Rg is the gravitational radius. The “relativistic light-bending model” is proposed to explain these observed features, where a compact X-ray source (“lamp post”) above an extreme Kerr black hole illuminates the innermost area of the accretion disc. In this paper, we critically examine the relativistic light-bending model by computing the rms spectra and the lag features using a ray-tracing technique, when a lamp post moves vertically on the black hole spin axis. As a result, we found that the observed deep rms dip requires that the iron is extremely overabundant (≳10 solar), whereas the observed lag amplitude is consistent with the normal iron abundance. Furthermore, disappearance of the lag in the high-flux state requires a source height as high as ∼40 Rg, which contradicts the relativistically broad emission line feature. Our simulations agree with the data that the reverberation feature moves to lower frequencies with larger source height; however, if this scenario is correct, the simulations predict the detection of a clear Fe-K lag at low frequencies, which is not constrained in the data. Therefore, we conclude that the relativistic light-bending model may not explain the characteristic Fe-K spectral variations in Seyfert galaxies.
Percutaneous Screws and External Fixation in Frontal Sinus Anterior Wall Fractures
Authors: Uraloğlu Muhammet , Ural Alper , Livaoğlu Murat , Karaçal Naci
Published: March 2018

Fractures of the frontal sinus are frequently encountered injuries of maxillofacial fractures. The most common causes are traffic accidents, followed by sports-related injuries. There is still no consensus regarding the optimal management of frontal sinus fractures. The authors report a patient with depressed anterior wall fracture of the frontal sinus and superior orbital rim fracture. Reduction was performed by traction from 2 screws applied percutaneously to the depressed fragments and external fixation with an aluminum nasal splint. This technique is both minimally invasive and permits easy fixation in suitable patients.
MAIT cells contribute to protection against lethal influenza infectionin vivo
Authors: van Wilgenburg Bonnie , Loh Liyen , Chen Zhenjun , Pediongco Troi J , Wang Huimeng , Shi Mai , Zhao Zhe , Koutsakos Marios , Nüssing Simone , Sant Sneha , Wang Zhongfang , D’Souza Criselle , Almeida Catarina F , Kostenko Lyudmila , Eckle Sidonia BG , Meehan Bronwyn S , Godfrey Dale I , Reading Patrick C , Corbett Alexandra J , McCluskey James , Klenerman Paul , Kedzierska Katherine , Hinks Timothy SC
Published: March 2018

Mucosal associated invariant T (MAIT) cells are evolutionarily-conserved, innate-like lymphocytes which are abundant in human lungs and can contribute to protection against pulmonary bacterial infection. MAIT cells are also activated during human viral infections, yet it remains unknown whether MAIT cells play a significant protective or even detrimental role during viral infectionsin vivo. Using murine experimental challenge with two strains of influenza A virus, we show that MAIT cells accumulated and were activated early in infection, with upregulation of CD25, CD69 and Granzyme B, peaking at 5 days post infection. Activation was modulated via cytokines independently of MR1. MAIT cell-deficient MR1−/−mice showed enhanced weight loss and mortality to severe (H1N1) influenza. This was ameliorated by prior adoptive transfer of pulmonary MAIT cells in both immunocompetent and immunodeficient RAG2−/−γC−/−mice. Thus, MAIT cells contribute to protection during respiratory viral infections, and constitute a potential target for therapeutic manipulation.
Graph Peak Caller: calling ChIP-Seq Peaks on Graph-based Reference Genomes
Authors: Grytten Ivar , Rand Knut D. , Nederbragt Alexander J. , Storvik Geir O. , Glad Ingrid K. , Sandve Geir K.
Published: March 2018

Graph-based representations are considered to be the future for reference genomes, as they allow integrated representation of the steadily increasing data on individual variation. Currently available tools allow de novo assembly of graph-based reference genomes, alignment of new read sets to the graph representation as well as certain analyses like variant calling and haplotyping. We here present a first method for calling ChIP-Seq peaks on read data aligned to a graph-based reference genome. The method is a graph generalization of the peak caller MACS2, and is implemented in an open source tool, Graph Peak Caller. By using the existing tool vg to build a pan-genome of Arabidopsis thaliana, we validate our approach by showing that Graph Peak Caller with a pan-genome reference graph can trace variants within peaks that are not part of the linear reference genome, and find peaks that in general are more motif-enriched than those found by MACS2.
When to care and when to kill: termites shape their collective response based on stage of infection
Authors: Davis Hannah E. , Meconcelli Stefania , Radek Renate , McMahon Dino P.
Published: March 2018

Termites defend their colonies from disease using an array of social behaviours, including allogrooming, cannibalism, and burial. We tested how groups of eastern subterranean termites (Reticulitermes flavipes) deploy these behaviours when presented with a nestmate at different stages of infection with the entomopathogenic fungusMetarhizium anisopliae. As expected, the termites groomed pathogen-exposed individuals significantly more than mock-treated controls; however, grooming levels were significantly higher after spore germination than before. Cannibalism became prevalent only after exposed termites became visibly ill, and burial was rarely observed. These results demonstrate that termites employ different strategies depending on the stage of infection that they encounter. Grooming intensity is linked not only to pathogen presence, but also to germination status, and, given the temporal correlation between cannibalism and visible signs of illness, the host may play a role in triggering its own sacrifice.
No Evidence for Communication in the Complete Locked-in State
Authors: Spüler Martin
Published: March 2018

Enabling communication for patients in the complete locked-in state (CLIS) has been a major goal for Brain-Computer Interface (BCI) research over the past 20 years. Last year, two papers were published that claim to have reached this goal: (Chaudhary et al., 2017) were the first to report communication in CLIS using a method based on fNRIS. Few month later, (Guger et al., 2017) claimed that their EEG-based BCI system is able to restore communication in CLIS. This manuscript demonstrates methodological flaws in the analysis of both papers and that their conclusions are invalid. Further, the data from (Chaudhary et al., 2017) is reanalyzed to demonstrate that their results cannot be reproduced and that there is currently no scientifically sound evidence that demonstrates communication in CLIS.
Evolution favors aging in populations with assortative mating and strong pathogen pressure
Authors: Lenart Peter , Bienertová-Vašků Julie , Berec Luděk
Published: March 2018

Since at first sight aging seems to be omnipresent, many authors to this very day regard it as an inevitable consequence of the laws of physics. However, studies published in the past two decades have conclusively shown that a number of organisms do not age, or at least do not age on a scale comparable with other aging organisms. This disparity leads us to question why aging evolved in some organisms and not in others. We thus present a mathematical model which simulates evolution in a sexually reproducing population composed of aging and non-aging individuals. We have observed that aging individuals may outcompete non-aging individuals if they have a higher starting fertility or if the main mating pattern in the population is assortative mating. Furthermore, stronger pathogen pressure was found to help the aging phenotype when compared to the non-aging phenotype. Last but not least, the aging phenotype was found to more easily outcompete the non-aging one or to resist the dominance of the latter for a longer period of time in populations composed of dimorphic sexually reproducing individuals compared to populations of hermaphrodites. Our findings are consistent with both classical evolutionary theories of aging and with evolutionary theories of aging which assume the existence of an aging program. They can thus potentially work as a bridge between these two opposing views, suggesting that the truth in fact lies somewhere in between.

Significance Statement

This study presents the first mathematical model which simulates the evolution of aging in a population of sexually reproducing organisms. Our model shows that aging individuals may outcompete non-aging individuals in several scenarios known to occur in nature. Our work thus provides important insight into the question why aging has evolved in most, but not all, organisms.
Kinetic analysis methods applied to single motor protein trajectories
Authors: Nord A L , Pols A F , Depken M , Pedaci F
Published: March 2018

Molecular motors convert chemical or electrical energy into mechanical displacement, either linear or rotary. Under ideal circumstances, single-molecule measurements can spatially and temporally resolve individual steps of the motor, revealing important properties of the underlying mechanochemical process. Unfortunately, steps are often hard to resolve, as they are masked by thermal noise. In such cases, details of the mechanochemistry can nonetheless be recovered by analyzing the fluctuations in the recorded traces. Here, we expand upon existing statistical analysis methods, providing two new avenues to extract the motor step size, the effective number of rate-limiting chemical states per translocation step, and the compliance of the link between the motor position and the probe particle. We first demonstrate the power and limitations of these methods using simulated molecular motor trajectories, and we then apply these methods to experimental data of kinesin, the bacterial flagellar motor, and F1-ATPase.
Changes In The Axon Initiation Segment Of Thalamic Neurons In Response To Cyclical Stimulation
Authors: Zirkov Mark , Kolezeva Yelena
Published: March 2018

Changes to the axon initiation segment in frequently firing neurons are known to be important predictors of early disease states. Studying this phenomenon in thalamic neurons is critical to understanding the first insult implicated in multiple neuro-degenerative disorders. To study these changes we used cyclical stimulations using micro-electrodes to the axon initiation segment of mouse thalamic neurons. Numerical simulation results indicate that axon initiation segment water potential fluctuated sinusoidally on high voltage only. Fluctuations in the amplitude and trend were caused by calcium flow and storage resistance, respectively. The change in axon initiation segment-stored water was proportional to the change rate in water potential. Axon initiation segment diameter increased with fluctuations in calcium free media; moreover, it varied slightly under low voltage conditions. Our results indicate that the changes in axon initiation segment diameter were caused by changes in water potential, which can be attributed to subcellular gated calcium channels within the thalamic neurons.
Spatially clustered loci with multiple enhancers are frequent targets of HIV-1
Authors: Lucic Bojana , Chen Heng-Chang , Kuzman Maja , Zorita Eduard , Wegner Julia , Minneker Vera , Roukos Vassilis , Wang Wei , Fronza Raffaele , Schmidt Manfred , Benkirane Monsef , Stadhouders Ralph , Vlahovicek Kristian , Filion Guillaume J , Lusic Marina
Published: March 2018

HIV-1 recurrently targets active genes that are positioned in the outer shell of the nucleus and integrates in the proximity of the nuclear pore compartment. However, the genomic features of these genes and the relevance of their transcriptional activity for HIV-1 integration have so far remained unclear. Here we show that recurrently targeted genes are delineated with super-enhancer genomic elements and that they cluster in specific spatial compartments of the T cell nucleus. We further show that these gene clusters acquire their location at the nuclear periphery during the activation of T cells. The clustering of these genes along with their transcriptional activity are the major determinants of HIV-1 integration in T cells. Our results show for the first time the relevance of the spatial compartmentalization of the genome for HIV-1 integration, thus further strengthening the role of nuclear architecture in viral infection.
Glycosylation-dependent modulation of the lL-2 signaling axis determines Th17 differentiation and IL-10 production
Authors: Gabryšová Leona , Mann Elizabeth H. , Bradley Lydia , MacRae James I. , Whicher Charlotte , Hawrylowicz Catherine M. , Anastasiou Dimitrios , O’Garra Anne
Published: March 2018

Metabolism plays an essential role in shaping T helper (Th) cell responses including the production of pro-inflammatory cytokines, however the effects on IL-10 have not been investigated. We show that the glucose analogue 2-deoxyglucose (2DG) specifically inhibits Th1 and Th2 cell differentiation and accompanying IL-10 production. In contrast, 2DG promotes IL-17A production by Th17 cells, even in the presence of IL-2 known to limit Th17 differentiation, whilst totally abrogating the production of IL-10. Notably, rather than inhibiting glycolysis, 2DG acts through the inhibition of glycosylation, which is critical for IL-2Rα surface expression and downstream signaling in both mouse and man. Strikingly, IL-2 is essential for IL-10 production by Th17 cells, in contrast to its inhibitory effect on the production of IL-17A. Our study reveals a previously unappreciated, anti-inflammatory role for IL-2 in Th17 cell production of IL-10 and thus identifies a novel mechanism to limit Th17 pathogenicity.
Influence of SNF1 complex on growth, glucose metabolism and mitochondrial respiration ofSaccharomyces cerevisiae
Authors: Martinez-Ortiz Cecilia , Carrillo-Garmendia Andres , Correa-Romero Blanca Flor , Canizal-García Melina , González-Hernández Juan Carlos , Regalado-Gonzalez Carlos , Olivares-Marin Ivanna Karina , Madrigal-Perez Luis Alberto
Published: March 2018

The switch of mitochondrial respiration to fermentation as the main pathway to produce ATP through the increase of glycolytic flux is known as the Crabtree effect. The elucidation of the molecular mechanism of the Crabtree effect may have important applications in ethanol production and lay the groundwork for the Warburg effect, which is essential in the molecular etiology of cancer. A key piece in this mechanism could be Snf1p, which is a protein that participates in the nutritional response that includes glucose metabolism. Thus, this work aimed to recognize the role of the SNF1 complex on the glycolytic flux and mitochondrial respiration, to gain insights about its relationship with the Crabtree effect. Herein, we found that inSaccharomyces cerevisiaecells grown at 1% glucose, mutation ofSNF1gene decreased glycolytic flux, increased NAD(P)H, enhancedHXK2gene transcription, and decreased mitochondrial respiration. Meanwhile, the same mutation increased the mitochondrial respiration of cells grown at 10% glucose. Moreover,SNF4gene deletion increased respiration and growth at 1% of glucose. In the case of theGAL83gene, we did not detect any change in mitochondrial respiration or growth. Altogether, these findings indicate thatSNF1is vital to switch from mitochondrial respiration to fermentation.
snpAD: An ancient DNA genotype caller
Authors: Prüfer Kay
Published: March 2018

Motivation

The study of ancient genomes can elucidate the evolutionary past. However, analyses are complicated by base-modifications in ancient DNA molecules that result in errors in DNA sequences. These errors are particularly common near the ends of sequences and pose a challenge for genotype calling.

Results

I describe an expectation-maximization algorithm that estimates genotype frequencies and errors along sequences to allow for accurate genotype calling from ancient sequences. The implementation of this method, called snpAD, performs well on high-coverage ancient data, as shown by simulations and by subsampling the data of a high-coverage Neandertal genome. Although estimates for low-coverage genomes are less accurate, I am able to derive approximate estimates of heterozygosity from several low-coverage Neandertals. These estimates show that low heterozygosity, compared to modern humans, was common among Neandertals.

Availability

The C++ code of snpAD is freely available at http://bioinf.eva.mpg.de/snpAD/

Contact

pruefer@eva.mpg.de

Supplementary information

Supplementary data are available at Bioinformatics online.
A Machine Learning Approach Predicts Tissue-Specific Drug Adverse Events
Authors: Madhukar Neel S. , Gayvert Kaitlyn , Gilvary Coryandar , Elemento Olivier
Published: March 2018

One of the main causes for failure in the drug development pipeline or withdrawal post approval is the unexpected occurrence of severe drug adverse events. Even though such events should be detected by in vitro, in vivo, and human trials, they continue to unexpectedly arise at different stages of drug development causing costly clinical trial failures and market withdrawal. Inspired by the “moneyball” approach used in baseball to integrate diverse features to predict player success, we hypothesized that a similar approach could leverage existing adverse event and tissue-specific toxicity data to learn how to predict adverse events. We introduce MAESTER, a data-driven machine learning approach that integrates information on a compound’s structure, targets, and phenotypic effects with tissue-wide genomic profiling and our toxic target database to predict the probability of a compound presenting with different types of tissue-specific adverse events. When tested on 6 different types of adverse events MAESTER maintains a high accuracy, sensitivity, and specificity across both the training data and new test sets. Additionally, MAESTER scores could flag a number of drugs that were approved, but later withdrawn due to unknown adverse events – highlighting its potential to identify events missed by traditional methods. MAESTER can also be used to identify toxic targets for each tissue type. Overall MAESTER provides a broadly applicable framework to identify toxic targets and predict specific adverse events and can accelerate the drug development pipeline and drive the design of new safer compounds.
ModulOmics: Integrating Multi-Omics Data to Identify Cancer Driver Modules
Authors: Silverbush Dana , Cristea Simona , Yanovich Gali , Geiger Tamar , Beerenwinkel Niko , Sharan Roded
Published: March 2018

The identification of molecular pathways driving cancer progression is a fundamental unsolved problem in tumorigenesis, which can substantially further our understanding of cancer mechanisms and inform the development of targeted therapies. Most current approaches to address this problem use primarily somatic mutations, not fully exploiting additional layers of biological information. Here, we describe ModulOmics, a method to de novo identify cancer driver pathways, or modules, by integrating multiple data types (protein-protein interactions, mutual exclusivity of mutations or copy number alterations, transcriptional co-regulation, and RNA co-expression) into a single probabilistic model. To efficiently search the exponential space of candidate modules, ModulOmics employs a two-step optimization procedure that combines integer linear programming with stochastic search. Across several cancer types, ModulOmics identifies highly functionally connected modules enriched with cancer driver genes, outperforming state-of-the-art methods. For breast cancer subtypes, the inferred modules recapitulate known molecular mechanisms and suggest novel subtype-specific functionalities. These findings are supported by an independent patient cohort, as well as independent proteomic and phosphoproteomic datasets.
Exacerbation of atopic dermatitis symptoms by ustekinumab in psoriatic patients with elevated serum immunoglobulin E levels: Report of two cases
Authors: Ishiuji Yozo , Umezawa Yoshinori , Asahina Akihiko , Fukuta Hirotaka , Aizawa Norie , Yanaba Koichi , Nakagawa Hidemi
Published: March 2018

Psoriasis is a chronic inflammatory skin disease mainly mediated by a T‐helper cell subset, Th17 cells. Recently, increased levels of total serum immunoglobulin (Ig)E have been reported in a subset of psoriatic patients. Ustekinumab (UST) is one of the most commonly used biologic agents for the treatment of moderate to severe plaque psoriasis, and a previous report also documented effectiveness of UST for psoriatic patients with high serum IgE levels. We experienced two psoriatic patients with high serum IgE levels, in whom UST completely improved psoriasis but paradoxically provoked or exacerbated atopic dermatitis (AD)‐like symptoms. This reciprocal phenomenon suggests the shift of Th balance toward Th2, along with altered profiles of inflammatory cytokines. It appears prudent to consider the possibility of such adverse effects when treating psoriatic patients with UST with concomitant AD symptoms, a history of AD or high serum IgE levels.
Related plant species respond similarly to chronic anthropogenic disturbance: Implications for conservation decision‐making
Authors: Martínez‐Blancas Alejandra , Paz Horacio , Salazar Gerardo A. , Martorell Carlos
Published: March 2018

Many developing countries harbour large numbers of species that face little‐understood, gradual changes in their environment, including chronic anthropogenic disturbance (CAD), a high frequency but low intensity form of disturbance. These countries also lack the resources to study each species, so conservation practices have been generalized, assuming that complete taxonomic groups may be managed in the same ways. This approach could be justified if closely related species respond similarly to threats. We assessed if related species respond similarly to CAD, whether this affects phylogenetic diversity and if such patterns occur in different systems.

Species’ identity and abundance was recorded in 59 sites differing in CAD intensity in a semi‐arid grassland and a tropical dry forest in Mexico. Disturbance response indices were calculated for each species. Nested analysis of variance coupled with null models were applied to determine if generalizations within taxa are justified and which taxonomic level explained the most variation in disturbance response among species. We obtained phylogenetic trees using molecular data for the grassland and published data for the tropical forest. Phylogenetic signal was measured with Pagel's λ. Community mean phylogenetic distance was regressed on CAD.

Higher taxonomic levels explained more variation than expected by chance, indicating that related species respond similarly to CAD. However, only species in the same genus behaved similarly enough to make generalizations reliable. This is the result of an underlying, if modest, phylogenetic signal in CAD responses. Mean phylogenetic distance decreased with CAD in the grassland but not the tropical dry forest. This suggests that CAD was a stronger environmental filter in the grassland but weak in the tropical dry forest, where it was less intense.

Policy implications. Species inform us how their relatives respond to chronic anthropogenic disturbance (CAD), supporting the idea that generalizations in management are possible. However, this procedure is seemingly reliable only within genera, which explain over 80% of the accumulated variance in species’ CAD responses, and not within orders or families. CAD may reduce phylogenetic diversity, perhaps leading to ecosystem function loss.
Spatial variation in herbivory, climate and isolation predicts plant height and fruit phenotype in Plectritis congesta populations on islands
Authors: Skaien Cora L. , Arcese Peter
Published: March 2018

Climate and herbivory can each drive natural selection on plant traits but may interact to give rise to different patterns in trait distributions when surveyed across island populations. These different patterns may arise because the occurrence of ungulate herbivores often varies across archipelagos, potentially leading to strong and abrupt spatial heterogeneity in the direction or intensity of natural selection. In contrast, climate tends to vary gradually and thus is more likely to lead to gradual clines in trait values.

Population isolation may also affect trait values, given that random genetic drift may fix alleles or traits in the absence of gene flow or because gene flow between populations with similar or opposing selection pressures may augment or swamp the effects of selection.

Here, we estimate the independent and interactive effects of deer, climate and isolation on fruit phenotype and plant height in 285 Plectritis congesta populations at 77 island and 44 mainland sites in western North America.

Plectritis congesta is a palatable winter annual with two fruit phenotypes based on a simple Mendelian locus with clear dominance and heritable variation in height as a polygenic trait. Fruit phenotype and plant height were well predicted by deer occurrence; plants in populations with resident deer were short (15.0 ± 1.1 cm) and mainly expressed wingless fruits (73.0 ± 4.0%), whereas plants in populations without deer were 2.6 times taller (38.9 ± 5.3 cm) and only 9.0 ± 1.6% expressed wingless fruits.

Wingless fruits were less common in populations experiencing wetter conditions with more seasonal variability in temperatures, particularly in the absence of deer. In contrast, population isolation was unrelated to fruit phenotype, except in populations rarely exposed to deer, where plants expressed phenotypes more like those in populations without deer as isolation increased. Our results are consistent with the hypothesis that spatial variation in browsing by deer or other factors correlated with it contributes to population‐level variation in fruit phenotype and plant height in P. congesta and that climate leads to a modest spatial gradient in plant height.

Synthesis. The occurrence of deer at 285 island and mainland populations of Plectritis congesta predicted plant height and fruit phenotype, supporting the hypothesis that spatial variation in herbivory is a key factor affecting population‐level variation in the distribution of these heritable traits.
A pilot study evaluation of Marte Meo for divorced fathers
Authors: DeGarmo David S. , Jones Jeremy , Rains Laura A.
Published: March 2018

A Marte Meo strengths‐based video feedback programme for improving divorced fathers' self‐conceptions and parenting was tested. By identifying and reinforcing fathers' skills in child communication, we hypothesized that fathers would exhibit pre‐post improvements in fathering self‐evaluations and behaviours. Therapists treated eleven divorced fathers with three to five home‐visit, video feedback sessions over twelve months. Data showed reductions in harsh discipline and inept parenting, and some evidence of improvements in efficacy and father involvement. Changes in fathering identity were significantly associated with changes in parental efficacy (r = .47), harsh parenting (r = −.64), and inept parenting (r = −.42). Programme acceptability was rated high on positive experiences and low on negative experiences. The data suggest promise for promoting fathers' effective parenting, quality involvement and self‐conceptions through video feedback.

Practitioner points

Single fathers are relatively under‐represented in clinical treatment and evidence‐based science relative to practice with mothers and couples

This article shows evidence of promise for Marte Meo, a strengths‐based video feedback treatment, to improve parenting skills of at‐risk fathers

Reinforcing and building upon existing skills can be a complementary treatment component and/or an alternative to deficit‐based practice
‘Utterly Disgraceful’: Social Media and the Workplace
Authors: Barnes Alison , Balnave Nikola , Holland Peter
Published: March 2018

Social media use by Australian public servants has given rise to questions pertaining to their political rights, impartiality and privacy outside of work. Drawing on the recent case Starr v Department of Human Services these issues are explored. The findings suggest that social media use has heightened tensions around public servant's rights to comment on issues of the day, and its use by employees both inside and beyond the workplace remains contested terrain.