bluuebunny/crossref_metadata_2025 huggingface dataset:
Competition Rules in the European Economic Area
Authors: Nozari Fariborz
Published: March 2019

On October 22, 1991, after exhaustive negotiations between the European Community (EC) and the Member States of the European Free Trade Association (EFTA) an agreement on the formation of the European Economic Area (EEA) was reached. Hence, the foundation was laid for an economic and social unit embracing 19 countries and about 380 million people, forming the world's largest economic bloc and a regional single market responsible for ca.40 percent of the world trade.

The Agreement consists of a preamble and nine parts covering the objectives and principles, the four freedoms of movements of goods, persons, service and capital, provisions on competition and other common rules, horizontal policies relevant to the four freedoms, cooperation outside the four freedoms, institutional provisions, funding, and final provisions.
Recent Legal Developments in the Nordic Countries: A Selected Bibliography of Works Written in English, German, French, and Italian, 1982-1992
Authors: Haider Inger Eriksson
Published: March 2019

The purpose of this bibliography is to give the non-Scandinavian language speaker an opportunity to follow the legal developments within the last decade in Denmark, Finland, Iceland, Norway and Sweden. The bibliography does not claim to be comprehensive, but it reflects what has been received at the Swiss Institute of Comparative Law during the last ten years or thereabouts.

The compilation includes books, essays, reports and articles published between 1982 and 1992. Excluded are chapters in basic comparative legal treatises, encyclopedias and looseleaf works.
International Documentation
Authors: Schaaf Robert W.
Published: March 2019

A most welcome new United Nations reference tool is a cumulative Index to Resolutions of the Security Council, 1946-1991. This 277-page volume, prepared by the Dag Hammarskjold Library, carries document symbol ST/ LIB/SER.H/5 and UN sales number E.93.I.6. Although the UN publishes an annual compilation of Security Council resolutions, which includes an index, this is the first official index since the cumulation issued for the years 1946-1970.
First-principles study of carbon capture and storage properties of porous MnO2 octahedral molecular sieve OMS-5
Authors: Lawson Matthew , Horn Jarod , Wong-Ng Winnie , Espinal Laura , Lapidus Saul H. , Giang Nguyen Huong , Meng Yongtao , Suib Steven L. , Kaduk James A. , Li Lan
Published: March 2019

Based on the experimentally determined framework structure of porous MnO2 octahedral molecular sieve (OMS)-5, we used density functional theory-based calculations to evaluate the effect of Na+ cation on pore dimensionality and structural stability, and the interaction between CO2 and OMS-5. We quantified the formation energy of one CO2/unit tunnel and two CO2/unit tunnel, and projected the electronic density of states on the OMS-5 framework, CO2 molecules, and Na+ cations to reveal their individual contributions and bonding nature. Partial charge densities were also calculated to investigate CO2 adsorption behavior in the OMS-5. Our studies predict the initial stage and driving force for the adsorption of CO2 in the OMS-5, guiding the OMS material design for carbon capture and storage applications.
De regulatie van de hypothalamus-hypofyse-bijnier-as in de pathogenese van depressieve stoornissen
Authors: Goekoop J.G.
Published: March 2019

Samenvatting

De dexamethason-corticotrofin-releasing-hormoon (DEX-CRH)-test is de meest gevoelige test voor veranderingen in de regulatie van de hypothalamus-hypofyse-bijnier-as bij stemmingsstoornissen. Zowel in de premorbide toestand als tijdens de acute episoden van stemmingsstoornissen komt onder deze conditie een verhoogde cortisolreactie voor. Een irreversibele lage GAHA-concentratie kan aan dit regulatietekort een bijdrage leveren. Verhoogde noradrenerge en vasopressinerge activiteiten kunnen in de overgang naar hogere DEX-CRH-reacties tijdens de acute episode een rol spelen. De dexamethason-suppressie-test verschilt van de DEX-CRH-test door de afwezigheid van een externe CRH-belasting en ‘early escape’ in deze test is op specifieke wijze geassocieerd met het melancholische subsyndroom. Dit suggereert dat een endogeen verhoogde CRH-activiteit bij de overgang naar deze subcategorie is betrokken. Verhoogde CRH-activiteit is aangetoond en toenames van noradrenerge activiteit en 5-HT2a-receptoren en afnames van glucocorticoïd-receptor-functie, tryptofaan-concentratie en serotonine-afgifte kunnen een bijdrage leveren. De uiteindelijk resulterende hoge cortisol-concentraties lijken de ontwikkeling te kunnen bevorderen van een resttoestand met ‘early escape’ na herstel.
Lipiden en Psychiatrie Denk aan het lipofiele karakter van psychofarmaca
Authors: Deimann L.G.J.
Published: March 2019

De relatie tussen lipiden en psychiatrie heeft in het laatste decennium ruim aandacht gekregen, in dit tijdschrift door een bijdrage van Duits en Van Tilburg.

In vrijwel alle publicaties wordt echter voorbijgegaan aan:

▪

de mogelijke rol van eventuele psychofarmaca;

▪

het lipofiele karakter van bijna al deze middelen;

▪

hun daardoor vanzelfsprekende interacties met de lipiden.

Juist hiervoor vraagt deze beschouwing aandacht.
Meaning of work and personal protective factors among palliative care professionals
Authors: Moreno-Milan Beatriz , Cano-Vindel Antonio , Lopez-Dóriga Pedro , Medrano Leonardo Adrián , Breitbart William
Published: March 2019

Objective

Healthcare professionals who work in palliative care units face stressful life events on a daily basis, most notably death. For this reason, these professionals must be equipped with the necessary protective resources to help them cope with professional and personal burnout. Despite the well-recognized importance of the construct “meaning of work,” the role of this construct and its relationship with other variables is not well-understood. Our objective is to develop and evaluate a model that examines the mediating role of the meaning of work in a multidisciplinary group of palliative care professionals. Using this model, we sought to assess the relationships between meaning of work, perceived stress, personal protective factors (optimism, self-esteem, life satisfaction, personal growth, subjective vitality), and sociodemographic variables.

Method

Professionals (n = 189) from a wide range of disciplines (physicians, psychologists, nurses, social workers, nursing assistants, physical therapists, and chaplains) working in palliative care units at hospitals in Madrid and the Balearic Islands were recruited. Sociodemographic variables were collected and recorded. The following questionnaires were administered: Meaning of Work Questionnaire, Perceived Stress Questionnaire, Life Orientation Test-Revised, Satisfaction with Life Scale, Subjective Vitality Scale, Rosenberg Self-Esteem Scale, and the Personal Growth Scale.

Result

The explanatory value of the model was high, explaining 49.5% of the variance of life satisfaction, 43% of subjective vitality, and 36% of personal growth. The main findings of this study were as follow: (1) meaning of work and perceived stress were negatively correlated; (2) optimism and self-esteem mediated the effect of stress on the meaning attached to work among palliative care professionals; (3) the meaning of work mediated the effect of stress on subjective vitality, personal growth, and life satisfaction; and (4) vitality and personal growth directly influenced life satisfaction.

Significance of results

The proposed model showed a high explanatory value for the meaning professionals give to their work and also for perceived stress, personal protective factors, and sociodemographic variables. Our findings could have highly relevant practical implications for designing programs to promote the psychological well-being of healthcare professionals.
Effects of intrauterine growth restriction and postnatal nutrition on pediatric asthma in Bangladesh
Authors: Nozawa Y. , Hawlader M. D. H. , Ferdous F. , Raqib R. , Tofail F. , Ekström E.-C. , Wagatsuma Y.
Published: March 2019

Numerous studies have investigated the risk of developing asthma due to early-life experiences and environmental exposures. However, the influence of intrauterine growth restriction and postnatal undernutrition on childhood wheezing/asthma remains unclear. Thus, we examined the effects of both small for gestational age (SGA) and postnatal stunted growth on ever asthma among children in the rural areas in Bangladesh.

Multiple follow-up studies were conducted in a cohort of randomized clinical trial of nutrition interventions during pregnancy (the MINIMat trial). Overall, 1208 and 1697 children were followed-up for asthma at 4.5 and 10 years, respectively. Anthropometric measurements were obtained at various intervals from birth to 10 years of age. Ever asthma was identified using the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire.

Results showed that SGA was significantly associated with increased risk of ever asthma at 4.5 and 10 years after adjusting for sex, body mass index, socioeconomic status, family history of asthma, gestational age at birth, mother’s parity, mother’s age at birth and intervention trial arm [odds ratio (OR)=1.97 (95% confidence interval (CI): 1.34–2.90) and 1.86 (95% CI: 1.18–2.72)]. For the postnatal effect of undernutrition, stunting at 1 and 2 years was significantly associated with ever asthma at 4.5 and 10 years [1 year: OR=1.77 (95% CI: 1.22–2.57) and OR=1.72 (95% CI: 1.16–2.56), 2 years: OR=1.49 (95% CI: 1.06–2.10) and OR=1.41 (95% CI: 1.02–1.96)].

In conclusion, SGA and undernutrition during infancy has an influence on childhood asthma among children in Bangladesh, indicating the need for nutritional interventions early in life.
Introduction to the material study of global constitutional law
Authors: GOLDONI MARCO
Published: March 2019

The article addresses the question of how to study global constitutional law by suggesting a material methodology. Drawing from previous studies of the notion of the material constitution, both from materialist and institutionalist types (Marx, Mortati, Poulantzas), the article proposes to look at the development of global constitutional law, in its many instantiations, in terms of its relation with the state. Accounts of the autonomy of global constitutional law are requalified in terms of relative autonomy. More specifically, global constitutional law is conceived as a legal construction functional to the transformation of the contemporary state. From the perspective of the material study of constitutional law, the state is still deemed to be the main unit of analysis, but, at the same time, state-centred accounts based on an exceptionalist understanding of sovereignty are rejected as reductive and, at times, inaccurate.
Consuming Diet Supplemented with Either Red Wheat Bran or Soy Extract Changes Glucose and Insulin Levels in Female Obese Zucker Rats
Authors: Stamatikos Alexis D. , Davis Jeremy E. , Shay Neil F. , Ajuwon Kolapo M. , Deyhim Farzad , Banz William J.
Published: March 2019

Abstract. Type 2 diabetes mellitus is characterized by the inability to regulate blood glucose levels due to insulin resistance, resulting in hyperglycemia and hyperinsulinemia. Research has shown that consuming soy and fiber may protect against type 2 diabetes mellitus. We performed a study to determine whether supplementing diet with soy extract (0.5% weight of diet) or fiber (as red wheat bran; 11.4% weight of diet) would decrease serum insulin and blood glucose levels in a pre-diabetic/metabolic syndrome animal model. In our study, female obese Zucker rats were fed either a control diet (n = 8) or control diet supplemented with either soy extract (n = 7) or red wheat bran (n = 8) for seven weeks. Compared to rats consuming control diet, rats fed treatment diets had significantly lower (p-value < 0.05) fasting serum insulin (control = 19.34±1.6; soy extract = 11.1±1.54; red wheat bran = 12.4±1.11) and homeostatic model assessment of insulin resistance values (control = 2.16±0.22; soy extract = 1.22±0.21; red wheat bran = 1.54±0.16). Non-fasted blood glucose was also significantly lower (p-value < 0.05) in rats fed treatment diets compared to rats consuming control diet at weeks four (control = 102.63±5.67; soy extract = 80.14±2.13; red wheat bran = 82.63±3.16), six (control = 129.5±10.83; soy extract = 89.14±2.48; red wheat bran = 98.13±3.54), and seven (control = 122.25±8.95; soy extract = 89.14±4.52; red wheat bran = 84.75±4.15). Daily intake of soy extract and red wheat bran may protect against type 2 diabetes mellitus by maintaining normal glucose homeostasis.
The Expanding Footprint of Rapid Arctic Change
Authors: Moon Twila A. , Overeem Irina , Druckenmiller Matt , Holland Marika , Huntington Henry , Kling George , Lovecraft Amy Lauren , Miller Gifford , Scambos Ted , Schädel Christina , Schuur Edward A. G. , Trochim Erin , Wiese Francis , Williams Dee , Wong Gifford
Published: March 2019

Arctic land ice is melting, sea ice is decreasing, and permafrost is thawing. Changes in these Arctic elements are interconnected, and most interactions accelerate the rate of change. The changes affect infrastructure, economics, and cultures of people inside and outside of the Arctic, including in temperate and tropical regions, through sea level rise, worsening storm and hurricane impacts, and enhanced warming. Coastal communities worldwide are already experiencing more regular flooding, drinking water contamination, and coastal erosion. We describe and summarize the nature of change for Arctic permafrost, land ice, and sea ice, and its influences on lower latitudes, particularly the United States. We emphasize that impacts will worsen in the future unless individuals, businesses, communities, and policy makers proactively engage in mitigation and adaptation activities to reduce the effects of Arctic changes and safeguard people and society.
Physical Processes Driving the Response of the F2 Region Ionosphere to the 21 August 2017 Solar Eclipse at Millstone Hill
Authors: Wang Wenbin , Dang Tong , Lei Jiuhou , Zhang Shunrong , Zhang Binzheng , Burns Alan
Published: March 2019

The high‐resolution thermosphere‐ionosphere‐electrodynamics general circulation model has been used to investigate the response of F2 region electron density (Ne) at Millstone Hill (42.61°N, 71.48°W, maximum obscuration: 63%) to the Great American Solar Eclipse on 21 August 2017. Diagnostic analysis of model results shows that eclipse‐induced disturbance winds cause F2 region Ne changes directly by transporting plasma along field lines, indirectly by producing enhanced O/N2 ratio that contribute to the recovery of the ionosphere at and below the F2 peak after the maximum obscuration. Ambipolar diffusion reacts to plasma pressure gradient changes and modifies Ne profiles. Wind transport and ambipolar diffusion take effect from the early phase of the eclipse and show strong temporal and altitude variations. The recovery of F2 region electron density above the F2 peak is dominated by the wind transport and ambipolar diffusion; both move the plasma to higher altitudes from below the F2 peak when more ions are produced in the lower F2 region after the eclipse. As the moon shadow enters, maximizes, and leaves a particular observation site, the disturbance winds at the site change direction and their effects on the F2 region electron densities also vary, from pushing plasma downward during the eclipse to transporting it upward into the topside ionosphere after the eclipse. Chemical processes involving dimming solar radiation and changing composition, wind transport, and ambipolar diffusion together cause the time delay and asymmetric characteristic (fast decrease of Ne and slow recovery of the eclipse effects) of the topside ionospheric response seen in Millstone Hill incoherent scatter radar observations.
Observations of Low‐Latitude Traveling Ionospheric Disturbances by a 630.0‐nm Airglow Imager and the CHAMP Satellite Over Indonesia
Authors: Moral Aysegul Ceren , Shiokawa Kazuo , Suzuki Shin , Liu Huixin , Otsuka Yuichi , Yatini Clara Yoko
Published: March 2019

We report the first comparison of ground and satellite measurements of low‐latitude traveling ionospheric disturbances (TIDs). Three TID events were simultaneously observed by a 630.0‐nm airglow imager and the CHAllenging Minisatellite Payload (CHAMP) satellite at Kototabang, Indonesia (geographic coordinates: 0.2° S, 100.3° E, geomagnetic latitude: 10.6° S). In 630.0‐nm airglow images of all three events, there are clear southward‐moving structures. Events 1 and 2 are a single pulse with horizontal scales of ∼500–1,000 km. Event 3 shows five wave fronts with a horizontal scale size of 500–1,000 km. All three TIDs are medium‐scale TIDs. Horizontal wavelengths of both airglow intensity at an average emission altitude of 250 km and CHAMP neutral density variations measured at 400 km are estimated by fitting a sinusoidal function to the observed data. The estimated horizontal wavelengths for airglow and neutral density data are 1,031 and 880 km for event 1 and 560 and 420 km for event 3, respectively. These values between airglow and CHAMP are comparable, suggesting both instruments are observing the same wave. For event 1, the CHAMP electron density mapped along the geomagnetic field line onto the airglow altitude does not show wave structure similar to the airglow variation. For events 2 and 3, the plasma density did not show wavy structures similar to the waves seen in the airglow image and CHAMP neutral density. These results suggest that the TIDs observed in airglow images are not caused by ionospheric plasma instability but by gravity waves in the thermosphere.
Solar Cycle Variability of Nonmigrating Tides in the 5.3 and 15 μm Infrared Cooling of the Thermosphere (100–150 km) from SABER
Authors: Nischal N. , Oberheide J. , Mlynczak M. G. , Marsh D. R. , Gan Q.
Published: March 2019

This paper discusses the solar cycle variation of the DE3 and DE2 nonmigrating tides in the nitric oxide (NO) 5.3 μm and carbon dioxide (CO2) 15 μm infrared cooling between 100 and 150 km altitude and ±40° latitude. Tidal diagnostics of SABER NO and CO2 cooling rate data (2002–2013) indicate DE3 (DE2) amplitudes during solar maximum are on the order of 1 (0.5) nW/m3 in NO near 125 km, and on the order of 60 (30) nW/m3 in CO2 at 100 km, which translates into roughly 15–30% relative to the monthly zonal mean. The NO cooling shows a pronounced (factor of 10) solar cycle dependence (lower during solar minimum) while the CO2 cooling does not vary much from solar min to solar max. Photochemical modeling reproduces the observed solar cycle variability and allows one to delineate the physical reasons for the observed solar flux dependence of the tides in the infrared cooling, particularly in terms of warmer/colder background temperature versus smaller/larger tidal temperatures during solar max/min, in addition to cooling rate variations due to vertical tidal advection and tidal density variations. Our results suggest that (i) tides caused by tropospheric weather impose a substantial—and in the NO 5.3 μm case solar cycle dependent—modulation of the infrared cooling, mainly due to tidal temperature, and (ii) observed tides in the infrared cooling are a suitable proxy for tidal activity including its solar cycle dependence in a part of Earth's atmosphere where direct global temperature observations are lacking.
On the Evaluation of Data Quality in the OMNI Interplanetary Magnetic Field Database
Authors: Vokhmyanin M. V. , Stepanov N. A. , Sergeev V. A.
Published: March 2019

The OMNI database is formed by propagating the solar wind measured at around Lagrange point L1, whose result may differ from the actual solar wind in the vicinity of the bow shock nose. To test the quality of the OMNI database, we cross‐correlate the 2‐hr intervals of 1‐min interplanetary magnetic field (IMF) data provided mostly by ACE and WIND spacecraft with Geotail measurements in front of the bow shock (10,409 cases in 1997–2016). We used two metrics: Pearson correlation coefficient (CC) and prediction efficiency (PE). Confirming previous studies, we found that the prediction quality of actual IMF degrades continuously with increasing distance of OMNI spacecraft from the Sun‐Earth line, with the amounts of poor and good predictions become nearly equal for RYZ ≥ 65 RE (they constitute ~12% of the entire database). In roughly 20% of the analyzed data, low CC and PE values were the consequence of low IMF variability (a low signal‐to‐noise ratio). The remaining data set includes 42% of very good data (CC ≥ 0.8), 33% of relatively good data (0.5 ≤ CC < 0.8 and PE ≥ 0), 10% of data having correct variability but wrong absolute values (0.5 ≤ CC < 0.8 and PE < 0), and 15% of poor data (CC < 0.5). We also discovered that the OMNI data are generally of a good quality when the PC index of geomagnetic activity correlates well with the solar wind‐magnetosphere coupling factor suggested by Kan and Lee (1979, https://doi.org/10.1029/GL006i007p00577).
What Do People Drink When They Think Their Tap Water Isn’t Safe?
Authors: Cook Terri
Published: March 2019

An analysis of nationwide housing data shows that minority households disproportionately bear the multibillion-dollar economic burden that comes from believing their water is unsafe.
Natural history of multiple myeloma with de novo del(17p)
Authors: Lakshman Arjun , Painuly Utkarsh , Rajkumar S. Vincent , Ketterling Rhett P. , Kapoor Prashant , Greipp Patricia T. , Gertz Morie A. , Buadi Francis K. , Lacy Martha Q. , Dingli David , Dispenzieri Angela , Fonder Amie L. , Hayman Suzanne R. , Hobbs Miriam A. , Gonsalves Wilson I. , Hwa Yi Lisa , Leung Nelson , Go Ronald S. , Lin Yi , Kourelis Taxiarchis V. , Warsame Rahma , Lust John A. , Russell Stephen J. , Zeldenrust Steven R. , Kyle Robert A. , Kumar Shaji K.
Published: March 2019

We compared the outcomes of 310 patients with newly diagnosed multiple myeloma with del(17p) detected by FISH to patients with high-risk translocations (HRT) (n = 79) and standard-risk (SR) cytogenetics (n = 541). The median progression-free survival (PFS) following initial therapy for the three groups was 21.1, 22, and 30.1 months, respectively (P = 0.437- del(17p) vs. HRT); the median overall survival (OS) was 47.3, 79.1, and 109.8 months, respectively, (P = 0.007- del(17p) vs. HRT). PFS and OS for patients with relative loss of 17p (n = 21) were comparable to other patients with del(17p). The PFS was similar between the del(17p) and HRT groups when stratified for age, ISS stage or treatment. The OS of del(17p) and HRT groups were similar in presence of advanced age, ISS III stage or if patients did not receive a proteasome-inhibitor containing induction. ISS III stage, high LDH and HRT, but not the percentage of cells with del(17p) predicted shorter OS in patients with del(17p). The median OS for low (ISS I, normal LDH and no HRT), intermediate (neither low nor high-risk) and high-risk (ISS III and either elevated LDH or coexistent HRT) groups among del(17p) patients were 96.2, 45.4, and 22.8 months, respectively, allowing further risk stratification.
Universal nuclear focusing of confined electron spins
Authors: Markmann Sergej , Reichl Christian , Wegscheider Werner , Salis Gian
Published: March 2019

For spin-based quantum computation in semiconductors, dephasing of electron spins by a fluctuating background of nuclear spins is a main obstacle. Here we show that this nuclear background can be precisely controlled in generic quantum dots by periodically exciting electron spins. We demonstrate this universal phenomenon in many-electron GaAs/AlGaAs quantum dot ensembles using optical pump-probe spectroscopy. A feedback mechanism between the electron spin polarization and the nuclear system focuses the electron spin precession frequency into discrete spin modes. Employing such control of nuclear spin polarization, the electron spin lifetime within individual dots can surpass the limit of nuclear background fluctuations, thus substantially enhancing the spin coherence time. This opens the door to achieve long electron spin coherence times also in lithographically defined many-electron systems that can be controlled in shape, size and position.
The molecular logic of Nanog-induced self-renewal in mouse embryonic stem cells
Authors: Heurtier Victor , Owens Nick , Gonzalez Inma , Mueller Florian , Proux Caroline , Mornico Damien , Clerc Philippe , Dubois Agnes , Navarro Pablo
Published: March 2019

Transcription factor networks, together with histone modifications and signalling pathways, underlie the establishment and maintenance of gene regulatory architectures associated with the molecular identity of each cell type. However, how master transcription factors individually impact the epigenomic landscape and orchestrate the behaviour of regulatory networks under different environmental constraints is only partially understood. Here, we show that the transcription factor Nanog deploys multiple distinct mechanisms to enhance embryonic stem cell self-renewal. In the presence of LIF, which fosters self-renewal, Nanog rewires the pluripotency network by promoting chromatin accessibility and binding of other pluripotency factors to thousands of enhancers. In the absence of LIF, Nanog blocks differentiation by sustaining H3K27me3, a repressive histone mark, at developmental regulators. Among those, we show that the repression of Otx2 plays a preponderant role. Our results underscore the versatility of master transcription factors, such as Nanog, to globally influence gene regulation during developmental processes.
Publisher Correction: Multi-experiment nonlinear mixed effect modeling of single-cell translation kinetics after transfection
Authors: Fröhlich Fabian , Reiser Anita , Fink Laura , Woschée Daniel , Ligon Thomas , Theis Fabian Joachim , Rädler Joachim Oskar , Hasenauer Jan
Published: March 2019

The original version of this Article had an incorrect Article number of 1, an incorrect Volume of 5 and an incorrect Publication year of 2019. These errors have now been corrected in the PDF and HTML versions of the Article.
MTrack: Automated Detection, Tracking, and Analysis of Dynamic Microtubules
Authors: Kapoor Varun , Hirst William G. , Hentschel Christoph , Preibisch Stephan , Reber Simone
Published: March 2019

Microtubules are polar, dynamic filaments fundamental to many cellular processes. In vitro reconstitution approaches with purified tubulin are essential to elucidate different aspects of microtubule behavior. To date, deriving data from fluorescence microscopy images by manually creating and analyzing kymographs is still commonplace. Here, we present MTrack, implemented as a plug-in for the open-source platform Fiji, which automatically identifies and tracks dynamic microtubules with sub-pixel resolution using advanced objection recognition. MTrack provides automatic data interpretation yielding relevant parameters of microtubule dynamic instability together with population statistics. The application of our software produces unbiased and comparable quantitative datasets in a fully automated fashion. This helps the experimentalist to achieve higher reproducibility at higher throughput on a user-friendly platform. We use simulated data and real data to benchmark our algorithm and show that it reliably detects, tracks, and analyzes dynamic microtubules and achieves sub-pixel precision even at low signal-to-noise ratios.
Multimodal floral cues guide mosquitoes to tansy inflorescences
Authors: Peach Daniel A. H. , Gries Regine , Zhai Huimin , Young Nathan , Gries Gerhard
Published: March 2019

Female mosquitoes exploit olfactory, CO2, visual, and thermal cues to locate vertebrate hosts. Male and female mosquitoes also consume floral nectar that provides essential energy for flight and survival. Heretofore, nectar-foraging mosquitoes were thought to be guided solely by floral odorants. Using common tansies,Tanacetum vulgareL., northern house mosquitoes,Culex pipiensL., and yellow fever mosquitoes,Aedes aegypti(L.), we tested the hypothesis that the entire inflorescence Gestalt of olfactory, CO2and visual cues is more attractive to mosquitoes than floral odorants alone. In laboratory experiments, we demonstrated that visual and olfactory inflorescence cues in combination attract more mosquitoes than olfactory cues alone. We established that tansies become net producers of CO2after sunset, and that CO2enhances the attractiveness of a floral blend comprising 20 synthetic odorants of tansy inflorescences. This blend included nine odorants found in human headspace. The “human-odorant-blend” attracted mosquitoes but was less effective than the entire 20-odorant floral blend. Our data support the hypothesis that the entire inflorescence Gestalt of olfactory, CO2and visual cues is more attractive to mosquitoes than floral odorants alone. Overlapping cues between plants and vertebrates support the previously postulated concept that haematophagy of mosquitoes may have arisen from phytophagy.
Mutational effects of human dopamine transporter at tyrosine88, lysine92, and histidine547 on basal and HIV-1 Tat-inhibited dopamine transport
Authors: Sun Wei-Lun , Quizon Pamela M. , Yuan Yaxia , Strauss Matthew J. , McCain Richard , Zhan Chang-Guo , Zhu Jun
Published: March 2019

Dysregulation of dopaminergic system induced by HIV-1 Tat protein-mediated direct inhibition of the dopamine transporter (DAT) has been implicated as a mediating factor of HIV-1 associated neurocognitive disorders. We have reported that single point mutations on human DAT (hDAT) at tyrosine88 (Y88F), lysine92 (K92M), and histidine547 (H547A) differentially regulate basal dopamine uptake but diminish Tat-induced inhibition of dopamine uptake by changing dopamine transport process. This study evaluated the effects of double (Y88F/H547A) and triple (Y88F/K92M/H547A) mutations on basal dopamine uptake, Tat-induced inhibition of DAT function, and dynamic transport process. Compared to wild-type hDAT, the Vmax values of [3H]Dopamine uptake were increased by 96% in Y88F/H547A but decreased by 97% in Y88F/K92M/H547A. [3H]WIN35,428 binding sites were not altered in Y88F/H547A but decreased in Y88F/K92M/H547A. Y88F/H547A mutant attenuated Tat-induced inhibition of dopamine uptake observed in wild-type hDAT. Y88F/H547A displayed an attenuation of zinc-augmented [3H]WIN35,428 binding, increased basal dopamine efflux, and reduced amphetamine-induced dopamine efflux, indicating this mutant alters transporter conformational transitions. These findings further demonstrate that both tyrosine88 and histidine547 on hDAT play a key role in stabilizing basal dopamine transport and Tat-DAT integration. This study provides mechanistic insights into developing small molecules to block multiple sites in DAT for Tat binding.
Mediterranean isolation preconditioning the Earth System for late Miocene climate cooling
Authors: Capella Walter , Flecker Rachel , Hernández-Molina F. Javier , Simon Dirk , Meijer Paul Th. , Rogerson Mike , Sierro Francisco J. , Krijgsman Wout
Published: March 2019

A global Neogene cooling trend culminated ~7 million years ago with the onset of Greenland glaciation. Increased ocean-atmosphere interaction and low- to high-latitude circulation are thought to be key factors in reorganizing late Miocene global temperature and precipitation patterns, but the drivers of this reorganization have yet to be identified. Here, we present new information about the evolution of the Atlantic-Mediterranean gateway that generated Mediterranean overflow. We use sedimentary and palaeogeographic evidence to constrain the timing and dimensions of this gateway and document the initiation of a saline plume of water within the North Atlantic. Today, this saline jet entrains and transports Eastern North Atlantic water and its dissolved inorganic carbon into the interior of the ocean, contributing to the drawdown of CO2 and the sensitivity of the ocean to atmospheric changes. We show that during the Miocene this transport emerged simultaneously with gateway restriction and propose that the resulting interaction of ocean-surface and ocean-interior carbon inventories would have greatly enhanced ocean-atmosphere exchange, preconditioning the Earth System for late Miocene cooling.
Interleukin-33 serum levels in postmenopausal women with osteoporosis
Authors: Ginaldi Lia , De Martinis Massimo , Saitta Salvatore , Sirufo Maria Maddalena , Mannucci Carmen , Casciaro Marco , Ciccarelli Fedra , Gangemi Sebastiano
Published: March 2019

There are many cytokines involved in the pathogenesis of osteoporosis. So far IL-33 involvement in osteoporotic patients has not yet been studied. IL-33 is a pro-inflammatory cytokine which mediates several immune functions; its involvement in a wide range of diseases, such as atopic dermatitis, asthma, and rheumatoid arthritis, is now emerging. In view of the crucial role of this cytokine in inflammation and bone remodeling, we measured IL-33 levels in the serum of postmenopausal women with osteoporosis. In 50 postmenopausal osteoporotic patients and 28 healthy postmenopausal control women, serum IL-33 levels were measured by enzyme linked immunosorbent assay. In both patients and controls the bone mineral density (BMD) was measured by double-energy X-ray absorptiometry (DXA). Vitamin D, calcium, alkaline phosphatase (ALP), parathyroid hormone (PTH) serum levels, as well as bone turnover markers, such as C-terminal telopeptide of type 1 collagen (CTX) and N-terminal propeptide of type 1 procollagen (P1NP) were also evaluated. In postmenopausal osteoporotic women IL-33 levels were significantly lower compared to healthy controls (3.53 ± 2.45 vs. 13.72 ± 5.39 pg/ml; P = 0.009) and positively correlated respectively with serum PTH (rho = 0.314; P = 0.026) and P1NP (rho = 0.373; P = 0.011) levels, while a statistically significant inverse correlation was observed between serum IL-33 and CTX levels (rho = −0.455; P = 0.002). Our results thus suggest that IL-33 represents an important bone-protecting cytokine which may be of therapeutic benefit in treating bone resorption.
Development of species specific putative miRNA and its target prediction tool in wheat (Triticum aestivum L.)
Authors: Jaiswal Sarika , Iquebal M. A. , Arora Vasu , Sheoran Sonia , Sharma Pradeep , Angadi U. B. , Dahiya Vikas , Singh Rajender , Tiwari Ratan , Singh G. P. , Rai Anil , Kumar Dinesh
Published: March 2019

MicroRNA are 20–24 nt, non-coding, single stranded molecule regulating traits and stress response. Tissue and time specific expression limits its detection, thus is major challenge in their discovery. Wheat has limited 119 miRNAs in MiRBase due to limitation of conservation based methodology where old and new miRNA genes gets excluded. This is due to origin of hexaploid wheat by three successive hybridization, older AA, BB and younger DD subgenome. Species specific miRNA prediction (SMIRP concept) based on 152 thermodynamic features of training dataset using support vector machine learning approach has improved prediction accuracy to 97.7%. This has been implemented in TamiRPred (http://webtom.cabgrid.res.in/tamirpred). We also report highest number of putative miRNA genes (4464) of wheat from whole genome sequence populated in database developed in PHP and MySQL. TamiRPred has predicted 2092 (>45.10%) additional miRNA which was not predicted by miRLocator. Predicted miRNAs have been validated by miRBase, small RNA libraries, secondary structure, degradome dataset, star miRNA and binding sites in wheat coding region. This tool can accelerate miRNA polymorphism discovery to be used in wheat trait improvement. Since it predicts chromosome-wise miRNA genes with their respective physical location thus can be transferred using linked SSR markers. This prediction approach can be used as model even in other polyploid crops.
Beta cell secretion of miR-375 to HDL is inversely associated with insulin secretion
Authors: Sedgeman Leslie R. , Beysen Carine , Ramirez Solano Marisol A. , Michell Danielle L. , Sheng Quanhu , Zhao Shilin , Turner Scott , Linton MacRae F. , Vickers Kasey C.
Published: March 2019

Extracellular microRNAs (miRNAs) are a new class of biomarkers for cellular phenotypes and disease, and are bioactive signals within intercellular communication networks. Previously, we reported that miRNAs are secreted from macrophage to high-density lipoproteins (HDL) and delivered to recipient cells to regulate gene expression. Despite the potential importance of HDL-miRNAs, regulation of HDL-miRNA export from cells has not been fully studied. Here, we report that pancreatic islets and beta cells abundantly export miR-375-3p to HDL and this process is inhibited by cellular mechanisms that promote insulin secretion. Small RNA sequencing and PCR approaches were used to quantify beta cell miRNA export to HDL. Strikingly, high glucose conditions were found to inhibit HDL-miR-375-3p export, which was dependent on extracellular calcium. Likewise, stimulation of cAMP was found to repress HDL-miR-375-3p export. Furthermore, we found that beta cell ATP-sensitive potassium channel (KATP) channels are required for HDL-miRNA export as chemical inhibition (tolbutamide) and global genetic knockout (Abcc8−/−) approaches inhibited HDL-miR-375-3p export. This process is not likely associated with cholesterol flux, as gain-of-function and loss-of-function studies for cholesterol transporters failed to alter HDL-miR-375-3p export. In conclusion, results support that pancreatic beta cells export miR-375-3p to HDL and this process is inversely regulated to insulin secretion.
GC-MS-based fecal metabolomics reveals gender-attributed fecal signatures in ankylosing spondylitis
Authors: He Zhixing , Wang Mingzhu , Li Haichang , Wen Chengping
Published: March 2019

Ankylosing spondylitis (AS) has different clinical features in males and females. Fecal metabolites play significant roles in AS disorders. This study aimed to reveal gender-attributed fecal signatures of AS. Fecal samples from 87 cross-sectional individuals (healthy controls: 20 males, 18 females; AS patients: 26 males, 23 females) were analyzed by gas chromatography-mass spectroscopy (GC-MS). Partial least squares discriminant analysis (PLS-DA) was used to reveal differences in the fecal signatures of AS between males and females. Fecal signatures were defined by the significantly different fecal metabolites between AS patients and healthy individuals. Therefore, different fecal signatures of male and female AS patients were defined as gender-attributed fecal signatures. Male-specific fecal signatures in AS patients were steroid compounds, including cholestan-3-ol, tocopherol, stigmastan-3,5-diene, cholest-3-ene, cholest-4-en-6-one and 1-heptatriacotanol. Female-specific fecal signatures were ergost-5-en-3-ol, acetate and D-myo-Inositol. Gender-attributed fecal signatures of AS further reveal differences between males and females in terms of AS features.
The association between low glucose-6-phosphate dehydrogenase activity level and hepatitis B virus infection among pre-pregnant reproductive-age Chinese females
Authors: Zhao Jun , Zhang Xu , Guan Ting , Dai Qiaoyun , He Wenshan , Zhang Hongguang , Wang Yuanyuan , Wang Bei , Peng Zuoqi , Hu Xuhuai , Qi Daxun , Yang Xueying , Zhang Yue , Ma Xu
Published: March 2019

The relationship between females with low glucose-6-phosphate dehydrogenase activity level (LG6PD) and HBV infection is unclear. We conducted a cross sectional study of 124 406 reproductive-age Chinese females who participated in the National Free Pre-conception Check-up Projects to investigate the risk of HBV infection among females with LG6PD and its effect on liver enzyme. Based on HBV serological test results, the participants were divided into the susceptible, immunized, and HBV infected groups. The multivariable-adjusted odds ratios (ORs) for HBV infection in LG6PD participants were 1.71 (95% confidence interval (CI): 1.45–2.01) and 1.41 (95% CI: 1.23–1.62), respectively with the susceptible and immunized participants as references, compared to those without LG6PD. Participants with HBV infection only and combined with HBV infection and LG6PD had 184% and 249% significantly higher risks of elevated alanine transaminase (ALT) (susceptible participants as reference). If the immunized participants were used as reference, significant higher odds of elevated ALT occurred (3.48 (95% CI: 3.18–3.80), 4.28 (95% CI: 2.92–6.28)). Thus, reproductive-age females with LG6PD had a higher prevalence of HBV infection, and LG6PD might exacerbate ALT elevation in HBV infected females. Our findings underscore the need to explore collaborative management approaches for these two diseases among reproductive-age females for maternal and child health.
Pathophysiological background and prognostic implication of systolic aortic root motion in non-ischemic dilated cardiomyopathy
Authors: Aurich Matthias , Niemers Matthias , Fuchs Patrick , Greiner Sebastian , Müller-Hennessen Matthias , Uhlmann Lorenz , Giannitsis Evangelos , Ehlermann Philipp , Meder Benjamin , Katus Hugo A. , Mereles Derliz
Published: March 2019

Recordings of aortic root movement represent one of the first accomplishments of ultrasound in medicine and mark the beginning of functional cardiac imaging. However, the underlying mechanism is not completely understood. Since the aortic root is directly connected to the cardiac skeleton we hypothesize, that the amplitude of systolic aortic root motion (SARM) may be mainly caused by displacement of the cardiac base towards the apex and might therefore be used as measure of left ventricular longitudinal function (LV-LF). One hundred and eighty patients with dilated cardiomyopathy and 180 healthy controls were prospectively included into this study. SARM was lower in patients compared to controls (9 ± 3 mm vs. 12 ± 2 mm, p < 0.001) and lowest in patients with cardiovascular events (9 ± 3 mm vs. 7 ± 3 mm, p < 0.001). During a median follow-up time of 38 months, the combined end-point of cardiovascular death or hospitalization for heart failure was reached by 25 patients (13.9%). Reduced SARM had significant prognostic impact on outcome (hazard ratio 0.74, 95% confidence interval 0.63–0.88, p < 0.001) and remained an independent predictor in the multivariate analysis. Compared to parameters with potential influence on its mechanism, SARM correlated best (r = 0.75, p < 0.001) with global longitudinal strain (GLS). SARM may therefore represent an alternative echocardiographic parameter for the assessment of LV-LF, particularly when GLS is not feasible or apical views are not available.
A deep learning approach to automatic teeth detection and numbering based on object detection in dental periapical films
Authors: Chen Hu , Zhang Kailai , Lyu Peijun , Li Hong , Zhang Ludan , Wu Ji , Lee Chin-Hui
Published: March 2019

We propose using faster regions with convolutional neural network features (faster R-CNN) in the TensorFlow tool package to detect and number teeth in dental periapical films. To improve detection precisions, we propose three post-processing techniques to supplement the baseline faster R-CNN according to certain prior domain knowledge. First, a filtering algorithm is constructed to delete overlapping boxes detected by faster R-CNN associated with the same tooth. Next, a neural network model is implemented to detect missing teeth. Finally, a rule-base module based on a teeth numbering system is proposed to match labels of detected teeth boxes to modify detected results that violate certain intuitive rules. The intersection-over-union (IOU) value between detected and ground truth boxes are calculated to obtain precisions and recalls on a test dataset. Results demonstrate that both precisions and recalls exceed 90% and the mean value of the IOU between detected boxes and ground truths also reaches 91%. Moreover, three dentists are also invited to manually annotate the test dataset (independently), which are then compared to labels obtained by our proposed algorithms. The results indicate that machines already perform close to the level of a junior dentist.
Using artificial neural networks to predict future dryland responses to human and climate disturbances
Authors: Buckland C. E. , Bailey R. M. , Thomas D. S. G.
Published: March 2019

Land degradation and sediment remobilisation in dryland environments is considered to be a significant global environmental problem. Given the potential for currently stabilised dune systems to reactivate under climate change and increased anthropogenic pressures, identifying the role of external disturbances in driving geomorphic response is vitally important. We developed a novel approach, using artificial neural networks (ANNs) applied to time series of historical reactivation-deposition events from the Nebraska Sandhills, to determine the relationship between historic periods of sand deposition in semi-arid grasslands and external climatic conditions, land use pressures and wildfire occurrence. We show that both vegetation growth and sediment re-deposition episodes can be accurately estimated. Sensitivity testing of individual factors shows that localised forcings (overgrazing and wildfire) have a statistically significant impact when the climate is held at present-day conditions. However, the dominant effect is climate-induced drought. Our approach has great potential for estimating future landscape sensitivity to climate and land use scenarios across a wide range of potentially fragile dryland environments.
First-in-human clinical study of novel technique to diagnose malignant melanoma via thermal conductivity measurements
Authors: Okabe Takahiro , Fujimura Taku , Okajima Junnosuke , Kambayashi Yumi , Aiba Setsuya , Maruyama Shigenao
Published: March 2019

Melanoma is an aggressive skin cancer that originates from melanocytes and, especially in the case of early-stage melanoma, is distributed adjacent to the epidermis and superficial dermis. Although early-stage melanoma can be distinguished from benign nevus via a dermoscopy, it is difficult to distinguish invasive melanoma in its early stages from in situ melanoma. Because invasive melanoma must undergo a sentinel lymph node biopsy to be diagnosed, a non-invasive method to detect the micro-invasion of early-stage melanoma is needed for dermato-oncologists. This paper proposes a novel quantitative melanoma identification method based on accurate measurements of thermal conductivity using a pen-shaped device. This method requires skin temperature data for one minute to determine the effective thermal conductivity of the skin, allowing it to distinguish melanoma lesions from healthy skin. Results suggest that effective thermal conductivity was negative for in situ melanoma. However, in accordance with tumour progression, effective thermal conductivity was larger in invasive melanoma. The proposed thermal conductivity measurement is a novel tool that detects the micro-invasion of melanoma.
A New GPS SNR-based Combination Approach for Land Surface Snow Depth Monitoring
Authors: Zhou Wei , Liu Lilong , Huang Liangke , Yao Yibin , Chen Jun , Li Songqing
Published: March 2019

Snow is not only a critical storage component in the hydrologic cycle but also an important data for climate research; however, snowfall observations are only sparsely available. Signal-to-noise ratio (SNR) has recently been applied for sensing snow depths. Most studies only consider either global positioning system (GPS) L1 or L2 SNR data. In the current study, a new snow depth estimation approach is proposed using multipath reflectometry and SNR combination of GPS triple frequency (i.e. L1, L2 and L5) signals. The SNR combination method describes the relationship between antenna height variation and spectral peak frequency. Snow depths are retrieved from the SNR combination data at YEL2 and KIRU sites and validated by comparing it with in situ observations. The elevation angle ranges from 5° to 25°. The correlations for the two sites are 0.99 and 0.97. The performance of the new approach is assessed by comparing it with existing models. The proposed approach presents a high correlation of 0.95 and an accuracy (in terms of Root Mean Square Error) improvement of over 30%. Findings indicate that the new approach could potentially be applied to monitor snow depths and may serve as a reference for building multi-system and multi-frequency global navigation satellite system reflectometry models.