bluuebunny/crossref_metadata_2025 huggingface dataset:
Health Selection, Migration, and HIV Infection in Malawi
Authors: Anglewicz Philip , VanLandingham Mark , Manda-Taylor Lucinda , Kohler Hans-Peter
Published: April 2018

Despite its importance in studies of migrant health, selectivity of migrants—also known as migration health selection—has seldom been examined in sub-Saharan Africa (SSA). This neglect is problematic because several features of the context in which migration occurs in SSA—very high levels of HIV, in particular—differ from contextual features in regions that have been studied more thoroughly. To address this important gap, we use longitudinal panel data from Malawi to examine whether migrants differ from nonmigrants in pre-migration health, assessed via SF-12 measures of mental and physical health. In addition to overall health selection, we focus on three more-specific factors that may affect the relationship between migration and health: (1) whether migration health selection differs by destination (rural-rural, rural-town, and rural-urban), (2) whether HIV infection moderates the relationship between migration and health, and (3) whether circular migrants differ in pre-migration health status. We find evidence of the healthy migrant phenomenon in Malawi, where physically healthier individuals are more likely to move. This relationship varies by migration destination, with healthier rural migrants moving to urban and other rural areas. We also find interactions between HIV-infected status and health: HIV-infected women moving to cities are physically healthier than their nonmigrant counterparts.
Crystallizations of constructs: Lessons learned from a literature review
Authors: Young Meredith E.
Published: April 2018

None
Diagnostic utility of glycosyltransferase mRNA expression in gastric cancer
Authors: Bhat Showkat Ahmad , Mir Manzoor Ur Rahman , Majid Sabhiya , Hassan Tehseen , Rehman Muneeb U. , Kuchy Sonallah
Published: April 2018

Objective/background:

Posttranslational modification of proteins, including glycosylation, is known to differ between normal and tumor cells. Altered glycosyltransferase levels have been observed in tumor tissues and their role in tumor metastasis and invasion has been implicated. In this study the role of altered glycosyltransferase messenger RNA (mRNA) levels in serum of gastric cancer patients as early markers of gastric cancer was evaluated.

Methods:

In this case control study the expression profile of ppGalNAc-T6, GlcNAcT-V, ST3Gal I, ST3 Gal IV, and ST6GalNAc-I in normal healthy control and gastric cancer patients was compared. Serum was isolated from blood samples of gastric cancer patients (n = 200) and controls (n = 200). Following RNA extraction, reverse transcription was carried out and transcript levels of glycosyltransferases were determined using real-time quantitative polymerase chain reaction and normalized against glyceraldehyde-3-phosphate dehydrogenase (GAPDH) expression. The amount of target gene, normalized to an endogenous reference gene relative to calibrator was calculated by using ΔΔCT method. Transcript levels in the serum samples of gastric cancer patients were compared with those of controls; also the same was correlated within sex and different stages of disease.

Results:

The mRNA expression of ppGalNAc-T6 and ST6GalNAc-I was significantly higher in serum samples of gastric cancer patients on comparison with controls (p = .008), however, there was no significant difference in mRNA expression of GlcNAcT-V, ST3Gal I, and ST3 Gal IV in serum samples of gastric cancer patients and controls (p = .097). In addition, no significant association of mRNA expression of these glycosyltransferases was found within sex and stages in this study.

Conclusion:

This study revealed the potential of ppGalNAc-T6 and ST6GalNAc-I mRNA transcript levels in serum as markers of gastric cancer. Further studies on the wider range of glycosyltransferases in various cancers are needed to establish signature mRNA batteries as minimally invasive markers of gastric cancer.
Characterization of superhydrophobic surfaces for drag reduction in turbulent flow
Authors: Gose James W. , Golovin Kevin , Boban Mathew , Mabry Joseph M. , Tuteja Anish , Perlin Marc , Ceccio Steven L.
Published: April 2018

A significant amount of the fuel consumed by marine vehicles is expended to overcome skin-friction drag resulting from turbulent boundary layer flows. Hence, a substantial reduction in this frictional drag would notably reduce cost and environmental impact. Superhydrophobic surfaces (SHSs), which entrap a layer of air underwater, have shown promise in reducing drag in small-scale applications and/or in laminar flow conditions. Recently, the efficacy of these surfaces in reducing drag resulting from turbulent flows has been shown. In this work we examine four different, mechanically durable, large-scale SHSs. When evaluated in fully developed turbulent flow, in the height-based Reynolds number range of 10 000 to 30 000, significant drag reduction was observed on some of the surfaces, dependent on their exact morphology. We then discuss how neither the roughness of the SHSs, nor the conventional contact angle goniometry method of evaluating the non-wettability of SHSs at ambient pressure, can predict their drag reduction under turbulent flow conditions. Instead, we propose a new characterization parameter, based on the contact angle hysteresis at higher pressure, which aids in the rational design of randomly rough, friction-reducing SHSs. Overall, we find that both the contact angle hysteresis at higher pressure, and the non-dimensionalized surface roughness, must be minimized to achieve meaningful turbulent drag reduction. Further, we show that even SHSs that are considered hydrodynamically smooth can cause significant drag increase if these two parameters are not sufficiently minimized.
Paleoenvironmental and paleoclimatic interpretation of the stratigraphic sequence of Lezetxiki II Cave (Basque Country, Iberian Peninsula) inferred from small vertebrate assemblages
Authors: Garcia-Ibaibarriaga Naroa , Suárez-Bilbao Aitziber , Bailon Salvador , Arrizabalaga Alvaro , Iriarte-Chiapusso María-José , Arnold Lee , Demuro Martina , Murelaga Xabier
Published: April 2018

We present a paleoenvironmental and paleoclimatic reconstruction based on microfaunal assemblages preserved at Lezetxiki II Cave (Arrasate, Basque Country, Iberian Peninsula) and synthesize previously published and new chronological work from the cave to better understand the environmental history of the region. The stratigraphic sequence of this short gallery ranges from the end of the middle Pleistocene to the middle Holocene and has great micropaleontological relevance for the Iberian Peninsula, especially because it contains the most ancient small vertebrate remains found in the Cantabrian region, likely deposited during Marine Oxygen Isotope Stage 7–6. Thirty-two small vertebrate taxa, including two extinct species, were identified. Environmental reconstruction based on small vertebrates suggests an open landscape at the base of the sequence (three lower levels) that progressively changed to woodland in the upper levels. Other paleoenvironmental data suggest a similar interpretation of the environmental history of the region, and although some uncertainty in the environmental reconstruction and chronology still exists, our data provide a richly detailed record of small vertebrates from an area that likely represented an important late Quaternary migration corridor for species traveling between the Iberian Peninsula and European continent.
Climate dynamics during the penultimate glacial period recorded in a speleothem from Kanaan Cave, Lebanon (central Levant)
Authors: Nehme Carole , Verheyden Sophie , Breitenbach Sebastian F.M. , Gillikin David P. , Verheyden Anouk , Cheng Hai , Edwards R. Lawrence , Hellstrom John , Noble Stephen R. , Farrant Andrew R. , Sahy Diana , Goovaerts Thomas , Salem Ghada , Claeys Philippe
Published: April 2018

Little is known about terrestrial climate dynamics in the Levant during the penultimate interglacial-glacial period. To decipher the palaeoclimatic history of the Marine Oxygen Isotope Stage (MIS) 6 glacial period, a well-dated stalagmite (~194 to ~154 ka) from Kanaan Cave on the Mediterranean coast in Lebanon was analyzed for its petrography, growth history, and stable isotope geochemistry. A resolved climate record has been recovered from this precisely U–Th dated speleothem, spanning the late MIS 7 and early MIS 6 at low resolution and the mid–MIS 6 at higher resolution. The stalagmite grew discontinuously from ~194 to ~163 ka. More consistent growth and higher growth rates between ~163 and ~154 ka are most probably linked to increased water recharge and thus more humid conditions. More distinct layering in the upper part of the speleothem suggests strong seasonality from ~163 ka to ~154 ka. Short-term oxygen and carbon isotope excursions were found between ~155 and ~163 ka. The inferred Kanaan Cave humid intervals during the mid–MIS 6 follow variations of pollen records in the Mediterranean basins and correlate well with the synthetic Greenland record and East Asian summer monsoon interstadial periods, indicating short warm/wet periods similar to the Dansgaard-Oeschger events during MIS 4–3 in the eastern Mediterranean region.
Skills and Core Competencies of Pharmacists in Humanitarian Assistance
Authors: Vardanyan Hamaspyur , Mosegui Gabriela Bittencourt Gonzalez , Miranda Elaine Silva
Published: April 2018

Background

Pharmacists’ participation in health care within multi-disciplinary teams in Humanitarian Assistance (HA) shall be encouraged. Limited literature exists on their role in the humanitarian context. The objective of this paper is to evidence the skill-specific, comprehensive core competencies that pharmacists must demonstrate working in humanitarian interventions.

Methods

The literature search laid the groundwork for the development of interview guides and further analysis of the data. Semi-structured interviews were conducted with expatriate pharmacists and medical coordinators, all of whom have worked in the field of HA. The interviews were recorded, transcribed, and analyzed using a content analysis methodology.

Results

Three pharmacists and three medical coordinators were interviewed, who had worked in a combined 32 humanitarian missions. The main functions of pharmacists were focused on stock management and supply of medicinal products. However, pharmacists in HA did not perform many functions related to the provision of effective medication therapy management (MTM). A core competency framework for pharmacists working in the humanitarian field was created, which reflects the personal and technical competencies that are essential to work in HA.

Conclusion

Self-management in a pressured and changing environment, the ability to adapt to changing situations, and planning, prioritizing, and performing tasks well under pressure are the skills required for pharmacists and for any other humanitarian health worker. The results highlight great efforts being dedicated to pharmaceutical product supply and management by pharmacists working in HA.

VardanyanH, MoseguiGBG, MirandaES. Skills and core competencies of pharmacists in humanitarian assistance. Prehosp Disaster Med. 2018;33(3):266–272.
ROBERT WIEBE'STHE SEARCH FOR ORDER, FIFTY YEARS ON
Authors: Tyrrell Ian
Published: April 2018

When invited to write this retrospective review, I turned to my library shelves to pick up once moreThe Search for Order, 1877–1920.My faded paperback copy has a striking image of a railroad track, peeling off into the distance, past a mine site, and then disappearing over the horizon. The colors are shades of red, a black tinged in the glow of red, and a pale pink sky. The scene conveys both an unsettling alarm at the turmoil of society in the coloration, and a binding process through the railroad. I have just discovered that Saul Lambert (a noted illustrator) drew this evocative scene for Hill and Wang, and the job was exceedingly well done.
The Contribution of Coping-Related Variables and Cardiac Vagal Activity on Prone Rifle Shooting Performance Under Pressure
Authors: Mosley Emma , Laborde Sylvain , Kavanagh Emma
Published: April 2018

Abstract. The aims of this study were to assess the predictive role of coping-related variables (CRV) on cardiac vagal activity (derived from heart rate variability), and to investigate the influence of CRV (and cardiac vagal activity) on prone rifle shooting performance under low pressure (LP) and high pressure (HP) conditions. Participants ( n = 38) competed in a shooting task under LP and HP. Cardiac vagal activity measurements were taken at baseline, task, and recovery for 5 min, alongside ratings of stress via a visual analogue scale. Upon task conclusion, self-report measures of motivation, stress appraisal, attention, perceived pressure, and trait CRV questionnaires (Decision-Specific Reinvestment Scale [DSRS], Movement-Specific Reinvestment Scale [MSRS], and Trait Emotional Intelligence Questionnaire [TEIQue]) were completed. Results indicated that task cardiac vagal activity was predicted by resting cardiac vagal activity and self-control in HP and LP. Post-task cardiac vagal activity was predicted by resting cardiac vagal activity in both conditions with the addition of a trait and state CRV in HP. Cardiac vagal reactivity, the change from resting to task, was predicted by resting cardiac vagal activity and self-control in LP and HP. Cardiac vagal recovery, the change from task to post-task, was predicted by a trait CRV in HP. Shooting performance was predicted by experience and cardiac vagal activity in LP and cardiac vagal activity and a trait in HP. Findings suggest both CRV and cardiac vagal activity influence cardiac vagal activity throughout a pressure task. Additionally, shooting performance directly influences cardiac vagal recovery.
A New Hybrid Method for Estimating Hydrologically Induced Vertical Deformation From GRACE and a Hydrological Model: An Example From Central North America
Authors: Karegar Makan A. , Dixon Timothy H. , Kusche Jürgen , Chambers Don P.
Published: April 2018

Hydrologically induced deformation of Earth's surface can be measured with high precision geodetic techniques, which in turn can be used to study the underlying hydrologic process. For geodetic study of other Earth processes such as tectonic and volcanic deformation, or coastal subsidence and its relation to relative sea level rise and flood risk, hydrological loading may be a source of systematic error, requiring accurate correction. Accurate estimation of the hydrologic loading deformation may require consideration of local as well as regional loading effects. We present a new hybrid approach to this problem, providing a mathematical basis for combining local (near field) and regional to global (far field) loading data with different accuracies and spatial resolutions. We use a high‐resolution hydrological model (WGHM) for the near field and GRACE data for the far field. The near field is defined as a spherical cap and its contribution is calculated using numerical evaluation of Green's functions. The far field covers the entire Earth, excluding only the near‐field cap. The far‐field contribution is calculated using a modified spherical harmonic approach. We test our method with a large GPS data set from central North America. Our new hybrid approach improves fits to GPS‐measured vertical displacements, with 25% and 35% average improvement relative to GRACE‐only or WGHM‐only spherical harmonic solutions. Our hybrid approach can be applied to a wide variety of environmental surface loading problems.
Effects of Uncertainties in the Atmospheric Density on the Probability of Collision Between Space Objects
Authors: Bussy‐Virat Charles D. , Ridley Aaron J. , Getchius Joel W.
Published: April 2018

The rapid increase of the number of objects in orbit around the Earth poses a serious threat to operational spacecraft and astronauts. In order to effectively avoid collisions, mission operators need to assess the risk of collision between the satellite and any other object whose orbit is likely to approach its trajectory. Several algorithms predict the probability of collision but have limitations that impair the accuracy of the prediction. An important limitation is that uncertainties in the atmospheric density are usually not taken into account in the propagation of the covariance matrix from current epoch to closest approach time. The atmosphere between 100 km and 700 km is strongly driven by solar and magnetospheric activity. Therefore, uncertainties in the drivers directly relate to uncertainties in the neutral density, hence in the drag acceleration. This results in important considerations for the prediction of Low Earth Orbits, especially for the determination of the probability of collision. This study shows how uncertainties in the atmospheric density can cause significant differences in the probability of collision and presents an algorithm that takes these uncertainties into account to more accurately assess the risk of collision. As an example, the effects of a geomagnetic storm on the probability of collision are illustrated.
Density‐Pressure Profiles of Fe‐Bearing MgSiO3 Liquid: Effects of Valence and Spin States, and Implications for the Chemical Evolution of the Lower Mantle
Authors: Karki Bijaya B. , Ghosh Dipta B. , Maharjan Charitra , Karato Shun‐ichiro , Park Jeffrey
Published: April 2018

Density is a key property controlling the chemical state of Earth's interior. Our knowledge about the density of relevant melt compositions is currently poor at deep‐mantle conditions. Here we report results from first‐principles molecular‐dynamics simulations of Fe‐bearing MgSiO3 liquids considering different valence and spin states of iron over the whole mantle pressure conditions. Our simulations predict the high‐spin to low‐spin transition in both ferrous and ferric iron in the silicate liquid to occur gradually at pressures around 100 GPa. The calculated iron‐induced changes in the melt density (about 8% increase for 25% iron content) are primarily due to the difference in atomic mass between Mg and Fe, with smaller contributions (<2%) from the valence and spin states. A comparison of the predicted density of mixtures of (Mg,Fe)(Si,Fe)O3 and (Mg,Fe)O liquids with the mantle density indicates that the density contrast between the melt and residual‐solid depends strongly on pressure (depth): in the shallow lower mantle (depths < 1,000 km), the melt is lighter than the solids, whereas in the deep lower mantle (e.g., the D″ layer), the melt density exceeds the mantle density when iron content is relatively high and/or melt is enriched with Fe‐rich ferropericlase.
Bedrock Erosion Surfaces Record Former East Antarctic Ice Sheet Extent
Authors: Paxman Guy J. G. , Jamieson Stewart S. R. , Ferraccioli Fausto , Bentley Michael J. , Ross Neil , Armadillo Egidio , Gasson Edward G. W. , Leitchenkov German , DeConto Robert M.
Published: April 2018

East Antarctica hosts large subglacial basins into which the East Antarctic Ice Sheet (EAIS) likely retreated during past warmer climates. However, the extent of retreat remains poorly constrained, making quantifying past and predicted future contributions to global sea level rise from these marine basins challenging. Geomorphological analysis and flexural modeling within the Wilkes Subglacial Basin are used to reconstruct the ice margin during warm intervals of the Oligocene‐Miocene. Flat‐lying bedrock plateaus are indicative of an ice sheet margin positioned >400–500 km inland of the modern grounding zone for extended periods of the Oligocene‐Miocene, equivalent to a 2‐m rise in global sea level. Our findings imply that if major EAIS retreat occurs in the future, isostatic rebound will enable the plateau surfaces to act as seeding points for extensive ice rises, thus limiting extensive ice margin retreat of the scale seen during the early EAIS.
Joint Inversion for Lithospheric Structures: Implications for the Growth and Deformation in Northeastern Tibetan Plateau
Authors: Deng Yangfan , Li Jiangtao , Song Xiaodong , Zhu Lupei
Published: April 2018

Several geodynamic models have been proposed for the deformation mechanism of Tibetan Plateau (TP), but it remains controversial. Here we applied a method of joint inversion of receiver functions and surface wave dispersions with P wave velocity constraint to a dense linear array in the NE Tibet. The results show that the geological blocks, separated by major faults at the surface, are characterized by distinct features in the crust, the Moho, and the uppermost mantle. The main features include crustal low‐velocity zones (LVZs) with variable strengths, anomalous Vp/Vs ratios that are correlated with LVZs, a large Moho jump, and other abrupt changes near major faults, strong mantle lithosphere anomalies, and correlation of crustal and mantle velocities. The results suggest a lithospheric‐scale deformation of continuous shortening as well as localized faulting, which is affected by the strength of the lithosphere blocks. The thickened mantle lithosphere can be removed, which facilitates the formation of middle‐lower crustal LVZ and flow. However, such flow is likely a consequence of the deformation rather than a driving force for the outward growth of the TP. The proposed model of TP deformation and growth can reconcile the continuous deformation within the blocks and major faults at the surface.
Potential role of CBX7 in regulating pluripotency of adult human pluripotent-like olfactory stem cells in stroke model
Authors: Fan Jia-Rong , Lee Hsu-Tung , Lee Wei , Lin Chen-Huan , Hsu Chun Y. , Hsieh Chia-Hung , Shyu Woei-Cherng
Published: April 2018

The adult olfactory mucosa, a highly regenerative tissue with unique life-long neurogenesis ability, is thought to harbor a naïve yet tightly controlled stem cell population. It will provide unique benefits in various stem cell-based therapies, such as stroke treatment. Here, we identified a subpopulation of adult pluripotent-like olfactory stem cells (APOSCs), which were modulated by an epigenetic repressor of CBX7. APOSCs form a floating sphere, express pluripotency markers Nanog, Oct-4, Sox-2, and SSEA-4 and show alkaline phosphatase activity. In addition, APOSCs display self-renewal and a pluripotent potential to differentiate into all three germ layers. Moreover, APOSCs coexpress pluripotency markers with CBX7. Within their natural niche, APOSCs from CBX7+/+ mice responded promptly to either spontaneous or injury-induced tissue regeneration. However, APOSCs from CBX7−/− mice manifested an impaired self-renewal and differentiation potential. Similarly, in vitro-cultivated CBX7−/− APOSCs underwent premature senescence, whereas CBX7+/+ APOSCs still actively divided, indicating that CBX7 is required for the self-renewal of APOSCs. Intracerebral implantation of APOSCs improved the stroke-mediated neurological dysfunction in rodents. These findings indicate that CBX7 plays a critical role in the regenerative properties of APOSCs and indicate the safety and feasibility of implantation of autologous APOSCs in stroke treatment.
GATA4 regulates angiogenesis and persistence of inflammation in rheumatoid arthritis
Authors: Jia Wanwan , Wu Weijun , Yang Di , Xiao Chenxi , Huang Mengwei , Long Fen , Su Zhenghua , Qin Ming , Liu Xinhua , Zhu Yi Zhun
Published: April 2018

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by abnormal inflammation, angiogenesis, and cartilage destruction. In RA, neoangiogenesis is an early and crucial event to promote the formation of pannus, causing further inflammatory cell infiltration. The transcription factor GATA4 is a critical regulator of cardiac differentiation-specific gene expression. We find that a higher level of GATA4 exists in synovium of rheumatoid arthritis (RA) patients, but the function of GATA4 in RA remains unclear. In the present study, IL-1β induces inflammation in fibroblast-like synoviocytes (FLS) MH7A, which is accompanied with the increased expression of GATA4 and VEGF production. Through application of GATA4 loss-of-function assays, we confirm the requirement of GATA4 expression for inflammation induced by IL-1β in FLS. In addition, we demonstrate for the first time that GATA4 plays key roles in regulating VEGF secretion from RA FLS to promote cellular proliferation, induce cell migration, and angiogenic tube formation of endothelial cells. GATA4 induces the angiogenic factors VEGFA and VEGFC, by directly binding to the promoter and enhancing transcription. The knockdown of GATA4 attenuates the development of collagen-induced arthritis (CIA) and prevents RA-augmented angiogenesis in vivo, which are accompanied with decreased VEGF level. These results reveal a previously unrecognized function for GATA4 as a regulator of RA angiogenesis and we provide experimental data validating the therapeutic target of GATA4 in RA mice.
Population coding of conditional probability distributions in dorsal premotor cortex
Authors: Glaser Joshua I. , Perich Matthew G. , Ramkumar Pavan , Miller Lee E. , Kording Konrad P.
Published: April 2018

Our bodies and the environment constrain our movements. For example, when our arm is fully outstretched, we cannot extend it further. More generally, the distribution of possible movements is conditioned on the state of our bodies in the environment, which is constantly changing. However, little is known about how the brain represents such distributions, and uses them in movement planning. Here, we record from dorsal premotor cortex (PMd) and primary motor cortex (M1) while monkeys reach to randomly placed targets. The hand’s position within the workspace creates probability distributions of possible upcoming targets, which affect movement trajectories and latencies. PMd, but not M1, neurons have increased activity when the monkey’s hand position makes it likely the upcoming movement will be in the neurons’ preferred directions. Across the population, PMd activity represents probability distributions of individual upcoming reaches, which depend on rapidly changing information about the body’s state in the environment.
Chemokines cooperate with TNF to provide protective anti-viral immunity and to enhance inflammation
Authors: Alejo Alí , Ruiz-Argüello M. Begoña , Pontejo Sergio M. , Fernández de Marco María del Mar , Saraiva Margarida , Hernáez Bruno , Alcamí Antonio
Published: April 2018

The role of cytokines and chemokines in anti-viral defense has been demonstrated, but their relative contribution to protective anti-viral responses in vivo is not fully understood. Cytokine response modifier D (CrmD) is a secreted receptor for TNF and lymphotoxin containing the smallpox virus-encoded chemokine receptor (SECRET) domain and is expressed by ectromelia virus, the causative agent of the smallpox-like disease mousepox. Here we show that CrmD is an essential virulence factor that controls natural killer cell activation and allows progression of fatal mousepox, and demonstrate that both SECRET and TNF binding domains are required for full CrmD activity. Vaccination with recombinant CrmD protects animals from lethal mousepox. These results indicate that a specific set of chemokines enhance the inflammatory and protective anti-viral responses mediated by TNF and lymphotoxin, and illustrate how viruses optimize anti-TNF strategies with the addition of a chemokine binding domain as soluble decoy receptors.
C/EBPβ regulates delta-secretase expression and mediates pathogenesis in mouse models of Alzheimer’s disease
Authors: Wang Zhi-Hao , Gong Ke , Liu Xia , Zhang Zhentao , Sun Xiaoou , Wei Zheng Zachory , Yu Shan Ping , Manfredsson Fredric P. , Sandoval Ivette M. , Johnson Peter F. , Jia Jianping , Wang Jian-Zhi , Ye Keqiang
Published: April 2018

Delta-secretase cleaves both APP and Tau to mediate the formation of amyloid plaques and neurofibrillary tangle in Alzheimer’s disease (AD). However, how aging contributes to an increase in delta-secretase expression and AD pathologies remains unclear. Here we show that a CCAAT-enhancer-binding protein (C/EBPβ), an inflammation-regulated transcription factor, acts as a key age-dependent effector elevating both delta-secretase (AEP) and inflammatory cytokines expression in mediating pathogenesis in AD mouse models. We find that C/EBPβ regulates delta-secretase transcription and protein levels in an age-dependent manner. Overexpression of C/EBPβ in young 3xTg mice increases delta-secretase and accelerates the pathological features including cognitive dysfunctions, which is abolished by inactive AEP C189S. Conversely, depletion of C/EBPβ from old 3xTg or 5XFAD mice diminishes delta-secretase and reduces AD pathologies, leading to amelioration of cognitive impairment in these AD mouse models. Thus, our findings support that C/EBPβ plays a pivotal role in AD pathogenesis via increasing delta-secretase expression.
Clinical and genomic landscape of gastric cancer with a mesenchymal phenotype
Authors: Oh Sang Cheul , Sohn Bo Hwa , Cheong Jae-Ho , Kim Sang-Bae , Lee Jae Eun , Park Ki Cheong , Lee Sang Ho , Park Jong-Lyul , Park Yun-Yong , Lee Hyun-Sung , Jang Hee-Jin , Park Eun Sung , Kim Sang-Cheol , Heo Jeonghoon , Chu In-Sun , Jang You-Jin , Mok Young-Jae , Jung WonKyung , Kim Baek-Hui , Kim Aeree , Cho Jae Yong , Lim Jae Yun , Hayashi Yuki , Song Shumei , Elimova Elena , Estralla Jeannelyn S. , Lee Jeffrey H. , Bhutani Manoop S. , Lu Yiling , Liu Wenbin , Lee Jeeyun , Kang Won Ki , Kim Sung , Noh Sung Hoon , Mills Gordon B. , Kim Seon-Young , Ajani Jaffer A. , Lee Ju-Seog
Published: April 2018

Gastric cancer is a heterogeneous cancer, making treatment responses difficult to predict. Here we show that we identify two distinct molecular subtypes, mesenchymal phenotype (MP) and epithelial phenotype (EP), by analyzing genomic and proteomic data. Molecularly, MP subtype tumors show high genomic integrity characterized by low mutation rates and microsatellite stability, whereas EP subtype tumors show low genomic integrity. Clinically, the MP subtype is associated with markedly poor survival and resistance to standard chemotherapy, whereas the EP subtype is associated with better survival rates and sensitivity to chemotherapy. Integrative analysis shows that signaling pathways driving epithelial-to-mesenchymal transition and insulin-like growth factor 1 (IGF1)/IGF1 receptor (IGF1R) pathway are highly activated in MP subtype tumors. Importantly, MP subtype cancer cells are more sensitive to inhibition of IGF1/IGF1R pathway than EP subtype. Detailed characterization of these two subtypes could identify novel therapeutic targets and useful biomarkers for prognosis and therapy response.
Rechargeable lithium-ion cell state of charge and defect detection by in-situ inside-out magnetic resonance imaging
Authors: Ilott Andrew J. , Mohammadi Mohaddese , Schauerman Christopher M. , Ganter Matthew J. , Jerschow Alexej
Published: April 2018

When and why does a rechargeable battery lose capacity or go bad? This is a question that is surprisingly difficult to answer; yet, it lies at the heart of progress in the fields of consumer electronics, electric vehicles, and electrical storage. The difficulty is related to the limited amount of information one can obtain from a cell without taking it apart and analyzing it destructively. Here, we demonstrate that the measurement of tiny induced magnetic field changes within a cell can be used to assess the level of lithium incorporation into the electrode materials, and diagnose certain cell flaws that could arise from assembly. The measurements are fast, can be performed on finished and unfinished cells, and most importantly, can be done nondestructively with cells that are compatible with commercial design requirements with conductive enclosures.
Measuring Integration Processes in Visual Symmetry with Frequency-Tagged EEG
Authors: Alp Nihan , Kohler Peter Jes , Kogo Naoki , Wagemans Johan , Norcia Anthony Matthew
Published: April 2018

Symmetry is a highly salient feature of the natural world which requires integration of visual features over space. The aim of the current work is to isolate dynamic neural correlates of symmetry-specific integration processes. We measured steady-state visual evoked potentials (SSVEP) as participants viewed symmetric patterns comprised of distinct spatial regions presented at two different frequencies (f1and f2). We measured intermodulation components, shown to reflect non-linear processing at the neural level, indicating integration of spatially separated parts of the pattern. We generated a wallpaper pattern containing two reflection symmetry axes by tiling the plane with a two-fold reflection symmetric unit-pattern and split each unit-pattern diagonally into separate parts which could be presented at different frequencies. We compared SSVEPs measured for wallpapers and control patterns for which both images were equal in terms of translation and rotation symmetry but reflection symmetry could only emerge for the wallpaper pattern through integration of the image-pairs. We found that low-frequency intermodulation components differed between the wallpaper and control stimuli, indicating the presence of integration mechanisms specific to reflection symmetry. These results showed that spatial integration specific to symmetry perception can be isolated through a combination of stimulus design and the frequency tagging approach.
Establishment and validation of the scoring system for preoperative prediction of central lymph node metastasis in papillary thyroid carcinoma
Authors: Liu Wen , Cheng Ruochuan , Ma Yunhai , Wang Dan , Su Yanjun , Diao Chang , Zhang Jianming , Qian Jun , Liu Jin
Published: April 2018

Early preoperative diagnosis of central lymph node metastasis (CNM) is crucial to improve survival rates among patients with papillary thyroid carcinoma (PTC). Here, we analyzed clinical data from 2862 PTC patients and developed a scoring system using multivariable logistic regression and testified by the validation group. The predictive diagnostic effectiveness of the scoring system was evaluated based on consistency, discrimination ability, and accuracy. The scoring system considered seven variables: gender, age, tumor size, microcalcification, resistance index >0.7, multiple nodular lesions, and extrathyroid extension. The area under the receiver operating characteristic curve (AUC) was 0.742, indicating a good discrimination. Using 5 points as a diagnostic threshold, the validation results for validation group had an AUC of 0.758, indicating good discrimination and consistency in the scoring system. The sensitivity of this predictive model for preoperative diagnosis of CNM was 4 times higher than a direct ultrasound diagnosis. These data indicate that the CNM prediction model would improve preoperative diagnostic sensitivity for CNM in patients with papillary thyroid carcinoma.
Synchronization by uncorrelated noise: interacting rhythms in interconnected oscillator networks
Authors: Meng John Hongyu , Riecke Hermann
Published: April 2018

Oscillators coupled in a network can synchronize with each other to yield a coherent population rhythm. How do multiple such rhythms interact with each other? Do these collective oscillations synchronize like individual oscillators? We show that this is not the case: for strong, inhibitory coupling rhythms can become synchronized by noise. In contrast to stochastic synchronization, this new mechanism synchronizes the rhythms even if the noisy inputs to different oscillators are completely uncorrelated. Key for the synchrony across networks is the reduced synchrony within the networks: it substantially increases the frequency range across which the networks can be entrained by other networks or by periodic pacemaker-like inputs. We demonstrate this type of robust synchronization for different classes of oscillators and network connectivities. The synchronization of different population rhythms is expected to be relevant for brain rhythms.
Applications of Bayesian network models in predicting types of hematological malignancies
Authors: Agrahari Rupesh , Foroushani Amir , Docking T. Roderick , Chang Linda , Duns Gerben , Hudoba Monika , Karsan Aly , Zare Habil
Published: April 2018

Network analysis is the preferred approach for the detection of subtle but coordinated changes in expression of an interacting and related set of genes. We introduce a novel method based on the analyses of coexpression networks and Bayesian networks, and we use this new method to classify two types of hematological malignancies; namely, acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Our classifier has an accuracy of 93%, a precision of 98%, and a recall of 90% on the training dataset (n = 366); which outperforms the results reported by other scholars on the same dataset. Although our training dataset consists of microarray data, our model has a remarkable performance on the RNA-Seq test dataset (n = 74, accuracy = 89%, precision = 88%, recall = 98%), which confirms that eigengenes are robust with respect to expression profiling technology. These signatures are useful in classification and correctly predicting the diagnosis. They might also provide valuable information about the underlying biology of diseases. Our network analysis approach is generalizable and can be useful for classifying other diseases based on gene expression profiles. Our previously published Pigengene package is publicly available through Bioconductor, which can be used to conveniently fit a Bayesian network to gene expression data.
A novel high sensitivity UPLC-MS/MS method for the evaluation of bisphenol A leaching from dental materials
Authors: De Nys Siemon , Putzeys Eveline , Vervliet Philippe , Covaci Adrian , Boonen Imke , Elskens Marc , Vanoirbeek Jeroen , Godderis Lode , Van Meerbeek Bart , Van Landuyt Kirsten L. , Duca Radu Corneliu
Published: April 2018

There is a growing necessity to acquire more profound knowledge on the quantity of eluates from resin-based dental materials, especially with regard to bisphenol A (BPA). The aim of the present study was to develop a highly sensitive method to characterize the short-term release of BPA in saliva with ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), using an extraction step and additional derivatization of BPA with pyridine-3-sulfonyl chloride. Light-cured resin-based composites were incubated at 37 °C in 1 mL artificial saliva, which was refreshed daily for one week. The final protocol allows accurate quantification of very low levels of BPA in samples of artificial saliva (i.e. 1.10 pmol BPA/mL or 250 pg/mL). The daily BPA-release from dental composites, ranging from 1.10 to 7.46 pmol BPA/mL, was characterized over a period of 7 days. The highest total amount of BPA was released from Solitaire 2 (24.72 ± 2.86 pmol), followed by G-ænial Posterior (15.51 ± 0.88 pmol) and Filtek Supreme XTE (12.00 ± 1.31 pmol). In contrast, only trace amounts of BPA were released from Ceram.x Universal. This UPLC-MS/MS method might be used for clinical research focusing on the evaluation of the clinical relevance of BPA release from dental materials.
Author Correction: The characterization of the circadian clock in the olive fly Bactrocera oleae (Diptera: Tephritidae) reveals a Drosophila-like organization
Authors: Bertolini Enrico , Kistenpfennig Christa , Menegazzi Pamela , Keller Alexander , Koukidou Martha , Helfrich-Förster Charlotte
Published: April 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.
Unsupervised Scalable Statistical Method for Identifying Influential Users in Online Social Networks
Authors: Azcorra A. , Chiroque L. F. , Cuevas R. , Fernández Anta A. , Laniado H. , Lillo R. E. , Romo J. , Sguera C.
Published: April 2018

Billions of users interact intensively every day via Online Social Networks (OSNs) such as Facebook, Twitter, or Google+. This makes OSNs an invaluable source of information, and channel of actuation, for sectors like advertising, marketing, or politics. To get the most of OSNs, analysts need to identify influential users that can be leveraged for promoting products, distributing messages, or improving the image of companies. In this report we propose a new unsupervised method, Massive Unsupervised Outlier Detection (MUOD), based on outliers detection, for providing support in the identification of influential users. MUOD is scalable, and can hence be used in large OSNs. Moreover, it labels the outliers as of shape, magnitude, or amplitude, depending of their features. This allows classifying the outlier users in multiple different classes, which are likely to include different types of influential users. Applying MUOD to a subset of roughly 400 million Google+ users, it has allowed identifying and discriminating automatically sets of outlier users, which present features associated to different definitions of influential users, like capacity to attract engagement, capacity to attract a large number of followers, or high infection capacity.
Characteristics of three organic matter pore types in the Wufeng-Longmaxi Shale of the Sichuan Basin, Southwest China
Authors: Nie Haikuan , Jin Zhijun , Zhang Jinchuan
Published: April 2018

A consensus has been reached through previous studies that organic matter (OM) pores are crucial to porosity in many shale gas reservoirs; however, their origins and types remain controversial. Here, we report the OM pore types hosted in algae, bitumen, graptolite and other fossil fragments in the Wufeng-Longmaxi Formations of the Sichuan Basin, Southwest China. Algae types mainly include multicellular algae, unicellular algae, etc. The OM pores in multicellular algae usually exhibit irregular, bubble-like, spherical and/or elliptical profiles, and their diameters vary between 300 and 800 nm. The shapes of the OM pores in unicellular algae are either irregular or oval, and the pores are hundreds of nanometres in size. The pores associated with solid bitumen are sporadic, isolated and variable in size, ranging from 500 nm to 3 μm. The pores in the graptolite, sponge spicule, radiolarian and other fossil fragments are much smaller and fewer. The pores may only have developed in the surface of the graptolite and bitumen by filling in the biological cavity of the sponge spicule. These new findings provide stronger evidence that multicellular algae are the main hydrocarbon generating organisms of OM pores development.
Molecular detection of fungal pathogens in clinical specimens by 18S rDNA high-throughput screening in comparison to ITS PCR and culture
Authors: Wagner K. , Springer B. , Pires V. P. , Keller P. M.
Published: April 2018

The rising incidence of invasive fungal infections and the expanding spectrum of fungal pathogens makes early and accurate identification of the causative pathogen a daunting task. Diagnostics using molecular markers enable rapid identification of fungi, offer new insights into infectious disease dynamics, and open new possibilities for infectious disease control and prevention. We performed a retrospective study using clinical specimens (N = 233) from patients with suspected fungal infection previously subjected to culture and/or internal transcribed spacer (ITS) PCR. We used these specimens to evaluate a high-throughput screening method for fungal detection using automated DNA extraction (QIASymphony), fungal ribosomal small subunit (18S) rDNA RT-PCR and amplicon sequencing. Fungal sequences were compared with sequences from the curated, commercially available SmartGene IDNS database for pathogen identification. Concordance between 18S rDNA RT-PCR and culture results was 91%, and congruence between 18S rDNA RT-PCR and ITS PCR results was 94%. In addition, 18S rDNA RT-PCR and Sanger sequencing detected fungal pathogens in culture negative (N = 13) and ITS PCR negative specimens (N = 12) from patients with a clinically confirmed fungal infection. Our results support the use of the 18S rDNA RT-PCR diagnostic workflow for rapid and accurate identification of fungal pathogens in clinical specimens.
Solvation-Guided Design of Fluorescent Probes for Discrimination of Amyloids
Authors: Cao Kevin J. , Elbel Kristyna M. , Cifelli Jessica L. , Cirera Jordi , Sigurdson Christina J. , Paesani Francesco , Theodorakis Emmanuel A. , Yang Jerry
Published: April 2018

The deposition of insoluble protein aggregates in the brain is a hallmark of many neurodegenerative diseases. While their exact role in neurodegeneration remains unclear, the presence of these amyloid deposits often precedes clinical symptoms. As a result, recent progress in imaging methods that utilize amyloid-specific small molecule probes have become a promising avenue for antemortem disease diagnosis. Here, we present a series of amino-aryl cyanoacrylate (AACA) fluorophores that show a turn-on fluorescence signal upon binding to amyloids in solution and in tissue. Using a theoretical model for environmental sensitivity of fluorescence together with ab initio computational modeling of the effects of polar environment on electron density distribution and conformational dynamics, we designed, synthesized, and evaluated a set of fluorophores that (1) bind to aggregated forms of Alzheimer’s-related β-amyloid peptides with low micromolar to high nanomolar affinities and (2) have the capability to fluorescently discriminate different amyloids based on differences in amino acid composition within the binding pocket through exploitation of their solvatochromic properties. These studies showcase the rational design of a family of amyloid-binding imaging agents that could be integrated with new optical approaches for the clinical diagnosis of amyloidoses, where accurate identification of the specific neurodegenerative disease could aid in the selection of a proper course for treatment.
Publisher Correction: Functional interaction between FUS and SMN underlies SMA-like splicing changes in wild-type hFUS mice
Authors: Mirra Alessia , Rossi Simona , Scaricamazza Silvia , Salvio Michela Di , Salvatori Illari , Valle Cristiana , Rusmini Paola , Poletti Angelo , Cestra Gianluca , Carrì Maria Teresa , Cozzolino Mauro
Published: April 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
Chromosomal barcoding as a tool for multiplexed phenotypic characterization of laboratory evolved lineages
Authors: Jahn Leonie Johanna , Porse Andreas , Munck Christian , Simon Daniel , Volkova Svetlana , Sommer Morten Otto Alexander
Published: April 2018

Adaptive laboratory evolution is an important tool to evolve organisms to increased tolerance towards different physical and chemical stress. It is applied to study the evolution of antibiotic resistance as well as genetic mechanisms underlying improvements in production strains. Adaptive evolution experiments can be automated in a high-throughput fashion. However, the characterization of the resulting lineages can become a time consuming task, when the performance of each lineage is evaluated individually. Here, we present a novel method for the markerless insertion of randomized genetic barcodes into the genome ofEscherichia coliusing a novel dual-auxotrophic selection approach. The barcodedE.colilibrary allows multiplexed phenotyping of evolved strains in pooled competition experiments. We use the barcoded library in an adaptive evolution experiment; evolving resistance towards three common antibiotics. Comparing this multiplexed phenotyping with conventional susceptibility testing and growth-rate measurements we can show a significant positive correlation between the two approaches. Use of barcoded bacterial strain libraries for individual adaptive evolution experiments drastically reduces the workload of characterizing the resulting phenotypes and enables prioritization of lineages for in-depth characterization. In addition, barcoded clones open up new ways to profile community dynamics or to track lineagesin vivoorsitu.