bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of immune profiles between hepatocellular carcinoma subtypes
Authors: Pan Xuemin , Lin Ping , Feng Fangyoumin , Li Jia , Li Yuan-Yuan , Dai Wentao , Hu Bo , Yang Xin-Rong , Fan Jia , Li Hong , Li Yixue
Published: January 2020

Immunotherapy, especially immune checkpoint inhibitors, is becoming a promising treatment for hepatocellular carcinoma (HCC). However, the response rate remains limited due to the heterogeneity of HCC samples. Molecular subtypes of HCC vary in genomic background, clinical features, and prognosis. This study aims to compare the immune profiles between HCC subtypes and find subtype-specific immune characteristics that might contribute to the prognosis and potential of immunotherapy. The immune profiles consist of immune-related genes, cytolytic
activity, immune pathways, and tumor-infiltrating lymphocytes. HCC-c1 samples showed an overall higher activation level of immune genes and pathways, and this pattern was consistent in validation sets. We associated the difference in immune profiles with the activation level of cancer hallmarks and genomic mutations. There was a negative correlation between most of the metabolism pathway
and immune-related pathways in HCC samples. CTNNB1/WNT signaling pathway mutation, one of the common mutations in HCC, appears to be associated with the expression of immune genes as well. These results reveal the difference of immune profiles between HCC subtypes and possible reasons and influence, which may also deepen our understanding of the carcinogenesis process.
Reflecting on place: environmental education as decolonisation
Authors: Thornton Simone , Graham Mary , Burgh Gilbert
Published: January 2020

We argue that to face climate change, all education, from kindergarten to tertiary, needs to be underpinned by environmental education. Moreover, as a site of reframing, education when coupled with philosophy is a possible site of influencing societal reframing in order to re-examine our relations to nature or our natural environment. However, we contend that as philosophy has been largely absent from curricula, it is vital to redress this issue. Further, the environment cannot be viewed simply as subject matter for study but, reconceptualised in the Indigenous sense as Place. Only in this way can we overcome the human-nature divide. We conclude that educators must look for what Plumwood calls ‘experiences that do not fit the dominant story’ to disrupt an important link in the chain of climate change by developing ‘traitorous identities’ able to challenge the dominant culture.
Assessment of degradation equivalent operating time for aircraft gas turbine engines
Authors: Alozie O. , Li Y.G. , Diakostefanis M. , Wu X. , Shong X. , Ren W.
Published: January 2020

This paper presents a novel method for quantifying the effect of ambient, environmental and operating conditions on the progression of degradation in aircraft gas turbines based on the measured engine and environmental parameters. The proposed equivalent operating time (EOT) model considers the degradation modes of fouling, erosion, and blade-tip wear due to creep strain, and expresses the actual degradation rate over the engine clock time relative to a pre-defined reference condition. In this work, the effects of changing environmental and engine operating conditions on the EOT for the core engine booster compressor and the high-pressure turbine were assessed by performance simulation with an engine model. The application to a single and multiple flight scenarios showed that, compared to the actual engine clock time, the EOT provides a clear description of component degradation, prediction of remaining useful life, and sufficient margin for maintenance action to be planned and performed before functional failure.
The implications of CEO power on the relationship between firm resources and innovation
Authors: Mousa Fariss-Terry , Chowdhury Jaideep , Gallagher Scott R.
Published: January 2020

We examine the link between firm resources and firm innovation intensity, especially the drivers of innovation and organizational slack. We extend the organizational slack and innovation literature by examining its interplay with CEO power and industry level constraints on that power. We examine the influence of human resource slack, CEO power, and industry concentration on R&D intensity. Our study examines all publicly traded US firms over a 10-year period, giving us over 13,400 firm years to look at. Our results indicate that organizations with excess human capacity do on average show higher investments in R&D. However, we also find that in concentrated industries, where CEOs are less constrained by competitive pressure, powerful CEOs do interfere in this strategic choice and weaken the slack–innovation relationship. Even though CEO's in these situations may have sufficient slack resources, they appear inclined to reallocate such resources to purposes other than innovation.
How Valuable Is a Presidential Cabinet? Measuring Ministries’ Political Attractiveness in Brazil
Authors: Mauerberg Arnaldo , Pereira Carlos
Published: January 2020

How valuable is a cabinet position? While the current literature does not ignore the reality that ministries differ from one another, it does not offer either theoretical or methodological procedures to assess such differences. This article introduces a refined measure of coalescence degree that considers several characteristics ministries may have, as well as politicians’ preferences about cabinet appointments. We estimate the effect of this alternative measure of coalescence on the president’s legislative success using large Brazilian datasets from 1995 to 2014 and an elite survey conducted with 62 Brazilian legislators. Controlling for other coalition management variables (coalition size and ideological heterogeneity), our refined coalescence metric turns out to be a more appropriate tool to assess the president’s performance in Congress.
A Troubled Collaboration:Cartonerosand the PRO Administrations in Buenos Aires
Authors: Gutiérrez Ricardo A.
Published: January 2020

Can popular organizations engage with the state in a lasting collaborative interaction that benefits their interests without being politically co-opted or captured? This article addresses this question by analyzing the interaction betweencartoneroorganizations and the PRO administrations in Buenos Aires City between 2002 and 2018. It shows howcartonerosmanaged to prompt a change in the PRO’s policies on recyclable waste collection. The article’s main arguments are that popular organizations’ opportunity to gain formal access to the state without losing their autonomy is related to the strategic orientations of both the popular organization and the ruling party, and that such a possibility increases when the popular organization is not part of the incumbent party coalition. The “troubled collaboration” betweencartonerosand the PRO was possible due both to thecartoneros’combination of contentious and institutionalized actions and to an important change in the PRO’s strategic orientation towardcartoneros.
Analysis of deficit irrigation strategies by using SUBSTOR-Potato model in a semi-arid area
Authors: Montoya F. , Camargo D. , Córcoles J. I. , Domínguez A. , Ortega J. F.
Published: January 2020

In areas where water is scarce, the use of regulated deficit irrigation, combined with decision support system tools, may decrease the impact of agriculture on natural water resources, as well as on energy consumption, thereby improving the profitability of farms. With this aim, the SUBSTOR-Potato model (incorporated in the DSSAT Program) was evaluated with a 2-year field test (2011 and 2012) conducted in a semi-arid area (Albacete, Spain) applying four irrigation levels (120, 100, 80 and 60% of irrigation requirements). Subsequently, the model was used for simulating the potato yield under several deficit irrigation strategies (ISs) during 30 years of a semi-arid climate (1988–2017) and determining the most profitable option. The considered ISs were deemed those most suitable from the yield and water productivity point of view by some authors. The model performance for tuber yield was satisfactory with an index of agreement >0.91 and errors between 0.71 and 3.06 × 103 kg/ha. The ISs simulated with SUBSTOR-Potato showed that slight deficit irrigation (5–10%) may increase the water productivity and profitability of the farms. Moreover, tuber formation (from onset of tuber initiation to harvest) was shown to be the most sensitive stage, therefore it is highly recommended to avoid deficit during this stage, which would cause a large reduction in yield (around 8 t/ha, depending on the level of deficit suffered by the crop).
The CaML model of pantheism
Authors: EFFINGHAM NIKK
Published: January 2020

This article argues for a new understanding of pantheism whereby God is a multi-located mereological simple which constitutes the cosmos. I argue that the traditional theist can more readily accept this version of pantheism than a version identifying God with the cosmos.1
IN OMNIBUS REGIONIBUS? THE FOURTEEN REGIONS AND THE CITY OF ROME
Authors: Goodman Penelope J.
Published: January 2020

Scholarship on the fourteen Augustan regions of Rome has tended to focus on their political and topographical significance. As a result, evidence for their social meaning and their impact on the mindsets and practices of the city's administrators and rulers has been under-exploited. This article seeks to address this lacuna. It begins by reviewing the history of Rome's regions and asking how and where the boundaries of the Augustan regions were recorded, before moving on to consider the impact of the regions on the Romans’ understanding and experiences of their city. This includes examining the evidence for bottom-up social identification with the regions, despite their top-down original creation. The paper also looks at the administrators who worked with the regions (regional magistrates and the food, water and fire services), arguing that the conceptual framework which the regions provided began to shape their working practices. Finally, it demonstrates the existence of a rhetoric of consistent provision across all fourteen regions, propagated especially by the emperors. The findings across all of these areas reveal that it is essential to take the regions and their impact into account when attempting to understand the topography of the city and the lives of its inhabitants.
Congenital ductus arteriosus aneurysm in association with MYH11 mutation: a case report
Authors: Ardhanari Mohanageetha , Swaminathan Sethuraman
Published: January 2020

Congenital ductus arteriosus aneurysms develop in the third trimester of fetal life, possibly due to abnormal intimal cushion formation or elastin expression in the ductal wall. It is often diagnosed in infants before 2 months of age. Most have a benign course and resolve spontaneously. However, life-threatening complications have been reported. We report a case of large ductal aneurysm diagnosed incidentally in a neonate, in whom there was a novel mutation in the smooth muscle myosin protein gene—MYH11.
Non-iodized salt consumption among women of reproductive age in sub-Saharan Africa: a population-based study
Authors: Ba Djibril M , Ssentongo Paddy , Liao Duanping , Du Ping , Kjerulff Kristen H
Published: January 2020

Objective:

To identify countries in sub-Saharan Africa (SSA) that have not yet achieved at least 90 % universal salt iodization and factors associated with the consumption of non-iodized salt among women of reproductive age.

Design:

A cross-sectional study using data from Demographic and Health Surveys (DHS). The presence of iodine in household salt (iodized or non-iodized), which was tested during the survey process, was the study outcome. Multivariable logistic regression models were used to determine independent factors associated with the consumption of non-iodized salt among women of reproductive age.

Setting:

There were eleven countries in SSA that participated in the DHS since 2015 and measured the presence of iodine in household salt.

Participants:

Women (n 108 318) aged 15–49 years.

Results:

Countries with the highest rate of non-iodized salt were Senegal (29·5 %) followed by Tanzania (21·3 %), Ethiopia (14·0 %), Malawi (11·6 %) and Angola (10·8 %). The rate of non-iodized salt was less than 1 % in Rwanda (0·3 %), Uganda (0·5 %) and Burundi (0·8 %). Stepwise multivariable logistic regression showed that women were more likely to be using non-iodized salt (adjusted OR; 95 % CI) if they were poor (1·62; 1·48, 1·78), pregnant (1·16; 1·04, 1·29), aged 15–24 years (v. older: 1·14; 1·04, 1·24) and were not literate (1·14; 1·06, 1·23).

Conclusions:

The use of non-iodized salt varies among SSA countries. The higher level of use of non-iodized salt among poor, young women and pregnant women is particularly concerning.
Acute toxicity profile of three-dimensional conformal concurrent chemoradiation in carcinoma cervix: an institutional experience
Authors: Tudu Rajanigandha , Kumar Anup , Singh Rashmi , Raina Payal
Published: January 2020

Background:

Concurrent chemoradiation is the definitive treatment for advanced cervical cancer. Pelvic radiation is known to damage the adjacent normal tissues thereby causing acute toxicities. The modern conformal radiation techniques like three-dimensional conformal radiotherapy (3D-CRT) and intensity-modulated radiotherapy are known to reduce the toxicities and improve clinical outcomes.

Aim:

To retrospectively evaluate the frequency and severity of acute toxicities encountered during concurrent chemoradiation of locally advanced cancer cervix treated with 3D-CRT.

Methods:

The medical case records of 174 cervical cancer patients treated between November 2015 and November 2018 were studied. One hundred and thirteen histologically proven locally advanced cancer cervix patients (Stage IIB–IIIB) treated with concurrent 3D conformal chemoradiation between were included in the study. Patients received 46 Gy in 23 fractions with concurrent weekly cisplatin (40 mg/m2) on days 1, 8, 15 and 22 of radiation. The study endpoints were treatment-related toxicities which were graded according to CTCAE version 5.0.

Results:

One hundred and thirteen patients were analysed for the study. Gastrointestinal toxicity was the predominant toxicity observed followed by haematological toxicity. 31·7% patients reported grade 1–2 diarrhoea and 39·7% reported grade 1–2 leucopenia. None of the patients reported grade 3 or higher toxicities. Treatment interruptions were noted due to these toxicities.

Conclusion:

Concurrent chemoradiation is the definitive treatment for locally advanced carcinoma cervix with acceptable toxicities. Proper management measures should be undertaken for these toxicities to avoid treatment interruptions and ensure better treatment compliance.
Impact of intra-fractional motion on dose distributions in lung IMRT
Authors: Chetvertkov Mikhail A. , Vassiliev Oleg N. , Yang Jinzhong , Wang He C. , Liu Amy Y. , Liao Zhongxing , Mohan Radhe
Published: January 2020

Aim:

To investigate the impact of intra-fractional motion on dose distribution in patients treated with intensity-modulated radiotherapy (IMRT) for lung cancer.

Materials and methods:

Twenty patients who had undergone IMRT for non-small cell lung cancer were selected for this retrospective study. For each patient, a four-dimensional computed tomography (CT) image set was acquired and clinical treatment plans were developed using the average CT. Dose distributions were then recalculated for each of the 10 phases of respiratory cycle and combined using deformable image registration to produce cumulative dose distributions that were compared with the clinical treatment plans.

Results:

Intra-fractional motion reduced planning target volume (PTV) coverage in all patients. The median reduction of PTV covered by the prescription isodose was 3·4%; D98 was reduced by 3·1 Gy. Changes in the mean lung dose were within ±0·7 Gy. V20 for the lung increased in most patients; the median increase was 1·6%. The dose to the spinal cord was unaffected by intra-fractional motion. The dose to the heart was slightly reduced in most patients. The median reduction in the mean heart dose was 0·22 Gy, and V30 was reduced by 2·5%. The maximum dose to the oesophagus was also reduced in most patients, by 0·74 Gy, whereas V50 did not change significantly. The median number of points in which dose differences exceeded 3%/3 mm was 6·2%.

Findings:

Intra-fractional anatomical changes reduce PTV coverage compared to the coverage predicted by clinical treatment planning systems that use the average CT for dose calculation. Doses to organs at risk were mostly over-predicted.
HO Generation Above Sprite‐Producing Thunderstorms Derived from Low‐Noise SMILES Observation Spectra
Authors: Yamada T. , Sato T. O. , Adachi T. , Winkler H. , Kuribayashi K. , Larsson R. , Yoshida N. , Takahashi Y. , Sato M. , Chen A. B. , Hsu R. R. , Nakano Y. , Fujinawa T. , Nara S. , Uchiyama Y. , Kasai Y.
Published: January 2020

No direct observational evidence of sprite‐produced active radicals has been presented owing to the difficulty of observing a small event area in the nighttime mesosphere, whereas sprite chemical models have indicated that sprite discharge locally affects the atmospheric composition. We present the first observational evidence of a HOproduction above sprite‐producing thunderstorms from the coincidence of temporal‐spatial observations of HOspectra, sprite events, and thunderstorms by two space instruments, a submillimeter‐wave limb spectrometer and ultraviolet/visible Imager and a ground‐based very low frequency radiation lightning detection network. A total of three areas was identified with enhanced HOlevels of approximately 10molecules. A chemical sprite model indicates an increase in HOin the considered altitude region; however, the predicted production due to a single sprite event is smaller than the observed enhancement. Our observational results suggest that sprites potentially contribute 1% of nighttime background HOgeneration at altitudes of 75–80 km globally.
Sugar, Gravel, Fish, and Flowers: Dependence of Mesoscale Patterns of Trade‐Wind Clouds on Environmental Conditions
Authors: Bony Sandrine , Schulz Hauke , Vial Jessica , Stevens Bjorn
Published: January 2020

Trade‐wind clouds exhibit a large diversity of spatial organizations at the mesoscale. Over the tropical western Atlantic, a recent study has visually identified four prominent mesoscale patterns of shallow convection, referred to as flowers, fish, gravel, and sugar. We show that these four patterns can be identified objectively from satellite observations by analyzing the spatial distribution of infrared brightness temperatures. By applying this analysis to 19 years of data, we examine relationships between cloud patterns and large‐scale environmental conditions. This investigation reveals that on daily and interannual timescales, the near‐surface wind speed and the strength of the lower‐tropospheric stability discriminate the occurrence of the different organization patterns. These results, combined with the tight relationship between cloud patterns, low‐level cloud amount, and cloud‐radiative effects, suggest that the mesoscale organization of shallow clouds might change under global warming. The role of shallow convective organization in determining low‐cloud feedback should thus be investigated.
Ion Cyclotron Resonant Absorption Lines in ELF Hiss Power Spectral Density in the Low‐Latitude Ionosphere
Authors: Chen Lunjin , Pfaff Robert , Heelis Roderick , Boardsen Scott , Xia Zhiyang
Published: January 2020

The effects of multiple ion species have been observed in electromagnetic wave spectra in both the ionosphere and the magnetosphere. Here we report an event from Communication/Navigation Outage Forecast System satellite, showing a new imprint of various ion species in observations of extremely low frequency (ELF) hiss wave spectra near the equatorial ionosphere, which presents minima in the power spectral density at gyrofrequencies and their harmonics of multiple ion species (e.g., O
and He
). Cyclotron harmonic resonant absorption is proposed to account for the observed spectral and polarization properties. Furthermore, the implication of using those wave power spectral minima to identify minor ion species in the ionosphere is discussed.
Clustering of Floating Tracer Due to Mesoscale Vortex and Submesoscale Fields
Authors: Stepanov Dmitry V. , Ryzhov Eugene A. , Zagumennov Alexei A. , Berloff Pavel , Koshel Konstantin V.
Published: January 2020

Floating tracer clustering is studied in oceanic flows that combine both a field of coherent mesoscale vortices, as simulated by a regional, comprehensive, eddy‐resolving general circulation model, and kinematic random submesoscale velocity fields. Both fields have rotational and divergent velocity components, and depending on their relative contributions, as well as on the local characteristics of the mesoscale vortices, we identified different clustering scenarios. We found that the mesoscale vortices do not prevent clustering but significantly modify its rate and spatial pattern. We also demonstrated that even weak surface‐velocity divergence has to be taken into account to avoid significant errors in model predictions of the floating tracer patterns. Our approach combining dynamically constrained and random velocity fields, and the applied diagnostic methods, are proposed as standard tools for analyses and predictions of floating tracer distributions, in both observational data and general circulation models.
Arctic Ocean Precipitation From Atmospheric Reanalyses and Comparisons With North Pole Drifting Station Records
Authors: Barrett Andrew P. , Stroeve Julienne C. , Serreze Mark C.
Published: January 2020

We evaluate fields of Arctic Ocean precipitation from six atmospheric reanalyses: NASA MERRA, NASA MERRA2, NOAA CFSR/CFSv2, ECMWF ERA‐Interim, ECMWF ERA5, and JMAO JRA55. The study is motivated by recognition that precipitation fields from reanalyses can serve as the key input into snow on sea ice accumulation models, supporting retrievals of sea ice thickness from satellite altimeter systems. Time series of annual precipitation over the central Arctic Ocean correlate well between all reanalyses, and they all capture the basic spatial and seasonal patterns of Arctic precipitation. However, they differ strongly with respect to precipitation amount: CFSR and MERRA2 are wetter than the other reanalyses. All reanalyses depict that the majority of total annual precipitation over the central Arctic Ocean comes from small events, less than 1 mm/day. Validation is challenged by sparse observations, uncertain adjustments for gauge undercatch, and other issues. However, given that correlations with data from Russian North Pole drifting station records are all roughly equal and that they depict similar interannual variability at the regional scale, all of the reanalyses appear suitable for supporting retrievals of ice thickness (provided that appropriate bias corrections can be applied). However, only CFSR, MERRA2, ERA5, and JRA55 will continue to generate output beyond 2019.
Shelf‐Break Upwelling and Productivity Over the North Kenya Banks: The Importance of Large‐Scale Ocean Dynamics
Authors: Jacobs Z. L. , Jebri F. , Raitsos D. E. , Popova E. , Srokosz M. , Painter S. C. , Nencioli F. , Roberts M. , Kamau J. , Palmer M. , Wihsgott J.
Published: January 2020

The North Kenya Banks (NKBs) have recently emerged as a new frontier for food security and could become an economically important fishery for Kenya with improved resources providing better accessibility. Little research has been done on the mechanisms supporting high fish productivity over the NKBs with information on annual and interannual environmental variability lacking. Here we use a high‐resolution, global, biogeochemical ocean model with remote sensing observations to demonstrate that the ocean circulation exerts an important control on the productivity over the NKBs. During the Northeast Monsoon, which occurs from December to February, upwelling occurs along the Kenyan coast, which is topographically enhanced over the NKBs. Additionally, enhanced upwelling events, associated with widespread cool temperatures, elevated chlorophyll, nutrients, primary production, and phytoplankton biomass, can occur over this region. Eight such modeled events, characterized by primary production exceeding 1.3 g C/m−2/day, were found to occur during January or February from 1993–2015. Even though the upwelling is always rooted to the NKBs, the position, spatial extent, and intensity of the upwelling exhibit considerable interannual variability. The confluence zone between the Somali Current and East African Coastal Current (referred to as the Somali‐Zanzibar Confluence Zone) forms during the Northeast Monsoon and is highly variable. We present evidence that when the Somali‐Zanzibar Confluence Zone is positioned further south, it acts to enhance shelf‐edge upwelling and productivity over the NKBs. These findings provide the first indication of the environmental controls that need to be considered when developing plans for the sustainable exploitation of the NKB fishery.
Electrical Resistivity of Freezing Clay: Experimental Study and Theoretical Model
Authors: Ming F. , Li D. Q. , Chen L.
Published: January 2020

Electrical resistivity of soil has become one of the most important indicators of compactness and compressive resistance. In previous studies, the temperature of soil tested was always above 0 °C. However, due to the phase change of pore water, the resistivity of freezing soils is different from that of unfrozen soils. Therefore, it is necessary to clarify the influence of temperature on electrical resistivity. To achieve this goal, according to the bundle of the cylindrical capillary model, pores in soil were treated as conducting tubes, and two simple lognormal functions were introduced to describe the distribution of the conducting tubes. Based on the conductivity theory, a new model considering the temperature and the pore size distribution was presented. Results show that only a part of the conducting tubes can be treated as the effective conducting tubes, which are determined by the soil temperature. Furthermore, a small portion of the pores with the smaller size controlled the electrical resistivity of the freezing clay. In other words, the change in the electrical resistivity of freezing clay was caused mainly by the change of unfrozen water content through the decrease in temperature. Based on the experimental results conducted on clay from Northeast China, the validity of the presented model was verified. The comparison results indicate that there was a good agreement between the calculated results and the experimental results. To expand the scope of the model, more laboratory tests are suggested to conduct to verify the applicability of the model to other clays.
Basin Evolution and Shale Tectonics on an Obliquely Convergent Margin: The Bahia Basin, Offshore Colombian Caribbean
Authors: Galindo Pedro A. , Lonergan Lidia
Published: January 2020

Oblique convergent margins accumulate strike‐slip deformation that controls basin formation and evolution. The Bahia Basin is located offshore, proximal to major strike‐slip fault systems that affect northern Colombia. It lies behind the toe of the modern accretionary prism, where the Caribbean Plate is being subducted obliquely beneath South America. This is the first attempt using 3‐D seismic reflection data to interpret a complex strike‐slip basin at the western end of the southern margin of the Caribbean Plate. Detailed 2‐D and 3‐D seismic mapping of regional unconformities and faults is used to describe the structural geometry, timing, and evolution of extensional and strike‐slip faults, which controlled the formation of the basin. Analysis of the fault zones is coupled with a description of the seismic‐stratigraphic units observed within the Bahia Basin to reconstruct the spatial and temporal evolution of deformation and to evaluate the influence of the pervasive shale tectonics observed in the area. The results, presented as a series of structural‐paleogeographic maps, illustrate an initial stage of transtension that controlled the formation of shale‐withdrawal minibasins from late Oligocene to late Miocene times. The continuous deformation and northward expulsion of the Santa Marta Massif resulted in transpression during Pliocene times, leading to basin inversion and ultimate closure of the basin. Basin evolution along the southern Caribbean oblique, convergent margin, shows the occurrence of a complex interaction between subduction and major‐onshore strike‐slip fault systems and illustrates how strain‐partitioning led to the break‐up and lateral displacement of early accretionary prisms formed along the margin.
Structural basis for itraconazole-mediated NPC1 inhibition
Authors: Long Tao , Qi Xiaofeng , Hassan Abdirahman , Liang Qiren , De Brabander Jef K. , Li Xiaochun
Published: January 2020

Niemann-Pick C1 (NPC1), a lysosomal protein of 13 transmembrane helices (TMs) and three lumenal domains, exports low-density-lipoprotein (LDL)-derived cholesterol from lysosomes. TMs 3–7 of NPC1 comprise the Sterol-Sensing Domain (SSD). Previous studies suggest that mutation of the NPC1-SSD or the addition of the anti-fungal drug itraconazole abolishes NPC1 activity in cells. However, the itraconazole binding site and the mechanism of NPC1-mediated cholesterol transport remain unknown. Here, we report a cryo-EM structure of human NPC1 bound to itraconazole, which reveals how this binding site in the center of NPC1 blocks a putative lumenal tunnel linked to the SSD. Functional assays confirm that blocking this tunnel abolishes NPC1-mediated cholesterol egress. Intriguingly, the palmitate anchor of Hedgehog occupies a similar site in the homologous tunnel of Patched, suggesting a conserved mechanism for sterol transport in this family of proteins and establishing a central function of their SSDs.
Chiral recognition and enantiomer excess determination based on emission wavelength change of AIEgen rotor
Authors: Hu Ming , Yuan Ying-Xue , Wang Weizhou , Li Dong-Mi , Zhang Hong-Chao , Wu Bai-Xing , Liu Minghua , Zheng Yan-Song
Published: January 2020

Chiral recognition, such as enantioselective interactions of enzyme with chiral agents, is one of the most important issues in the natural world. But artificial chiral receptors are much less efficient than natural ones. For tackling the chiral recognition and enantiomer excess (ee) analysis, up until now all the fluorescent receptors have been developed based on fluorescence intensity changes. Here we report that the chiral recognition of a large number of chiral carboxylic acids, including chiral agrochemicals 2,4-D, is carried out based on fluorescent colour changes rather than intensity changes of AIEgen rotors. Moreover, the fluorescence wavelength of the AIEgen rotor linearly changes with ee of the carboxylic acid, enabling the ee to be accurately measured with average absolute errors (AAE) of less than 2.8%. Theoretical calculation demonstrates that the wavelength change is ascribed to the rotation of the AIEgen rotor upon interaction with different enantiomers.
Robust, reproducible and quantitative analysis of thousands of proteomes by micro-flow LC–MS/MS
Authors: Bian Yangyang , Zheng Runsheng , Bayer Florian P. , Wong Cassandra , Chang Yun-Chien , Meng Chen , Zolg Daniel P. , Reinecke Maria , Zecha Jana , Wiechmann Svenja , Heinzlmeir Stephanie , Scherr Johannes , Hemmer Bernhard , Baynham Mike , Gingras Anne-Claude , Boychenko Oleksandr , Kuster Bernhard
Published: January 2020

Nano-flow liquid chromatography tandem mass spectrometry (nano-flow LC–MS/MS) is the mainstay in proteome research because of its excellent sensitivity but often comes at the expense of robustness. Here we show that micro-flow LC–MS/MS using a 1 × 150 mm column shows excellent reproducibility of chromatographic retention time (<0.3% coefficient of variation, CV) and protein quantification (<7.5% CV) using data from >2000 samples of human cell lines, tissues and body fluids. Deep proteome analysis identifies >9000 proteins and >120,000 peptides in 16 h and sample multiplexing using tandem mass tags increases throughput to 11 proteomes in 16 h. The system identifies >30,000 phosphopeptides in 12 h and protein-protein or protein-drug interaction experiments can be analyzed in 20 min per sample. We show that the same column can be used to analyze >7500 samples without apparent loss of performance. This study demonstrates that micro-flow LC–MS/MS is suitable for a broad range of proteomic applications.
Evolving parsec-scale radio structure in the most distant blazar known
Authors: An Tao , Mohan Prashanth , Zhang Yingkang , Frey Sándor , Yang Jun , Gabányi Krisztina É. , Gurvits Leonid I. , Paragi Zsolt , Perger Krisztina , Zheng Zhenya
Published: January 2020

Blazars are a sub-class of quasars with Doppler boosted jets oriented close to the line of sight, and thus efficient probes of supermassive black hole growth and their environment, especially at high redshifts. Here we report on Very Long Baseline Interferometry observations of a blazar J0906 + 6930 at z = 5.47, which enabled the detection of polarised emission and measurement of jet proper motion at parsec scales. The observations suggest a less powerful jet compared with the general blazar population, including lower proper motion and bulk Lorentz factor. This coupled with a previously inferred high accretion rate indicate a transition from an accretion radiative power to a jet mechanical power based transfer of energy and momentum to the surrounding gas. While alternative scenarios could not be fully ruled out, our results indicate a possibly nascent jet embedded in and interacting with a dense medium resulting in a jet bending.
Two-dimensional higher-order topology in monolayer graphdiyne
Authors: Lee Eunwoo , Kim Rokyeon , Ahn Junyeong , Yang Bohm-Jung
Published: January 2020

Based on first-principles calculations and tight-binding model analysis, we propose monolayer graphdiyne as a candidate material for a two-dimensional higher-order topological insulator protected by inversion symmetry. Despite the absence of chiral symmetry, the higher-order topology of monolayer graphdiyne is manifested in the filling anomaly and charge accumulation at two corners. Although its low energy band structure can be properly described by the tight-binding Hamiltonian constructed by using only the pz orbital of each atom, the corresponding bulk band topology is trivial. The nontrivial bulk topology can be correctly captured only when the contribution from the core levels derived from px,y and s orbitals are included, which is further confirmed by the Wilson loop calculations. We also show that the higher-order band topology of a monolayer graphdyine gives rise to the nontrivial band topology of the corresponding three-dimensional material, ABC-stacked graphdiyne, which hosts monopole nodal lines and hinge states.
Bile acid bio-nanoencapsulation improved drug targeted-delivery and pharmacological effects via cellular flux: 6-months diabetes preclinical study
Authors: Mooranian Armin , Raj Wagle Susbin , Kovacevic Bozica , Takechi Ryu , Mamo John , Lam Virginie , Watts Gerald F. , Mikov Momir , Golocorbin-Kon Svetlana , Stojanovic Goran , Al-Sallami Hesham , Al-Salami Hani
Published: January 2020

The antilipidemic drug, probucol (PB), has demonstrated potential applications in Type 2 diabetes (T2D) through its protective effects on pancreatic β-cells. PB has poor solubility and bioavailability, and despite attempts to improve its oral delivery, none has shown dramatic improvements in absorption or antidiabetic effects. Preliminary data has shown potential benefits from bile acid co-encapsulation with PB. One bile acid has shown best potential improvement of PB oral delivery (ursodeoxycholic acid, UDCA). This study aimed to examine PB and UDCA microcapsules (with UDCA microcapsules serving as control) in terms of the microcapsules’ morphology, biological effects ex vivo, and their hypoglycemic and antilipidemic and anti-inflammatory effects in vivo. PBUDCA and UDCA microcapsules were examined in vitro (formulation studies), ex vivo and in vivo. PBUDCA microcapsules exerted positive effects on β-cells viability at hyperglycemic state, and brought about hypoglycemic and anti-inflammatory effects on the prediabetic mice. In conclusion, PBUDCA co-encapsulation have showed beneficial therapeutic impact of dual antioxidant-bile acid effects in diabetes treatment.
SWeeP: representing large biological sequences datasets in compact vectors
Authors: De Pierri Camilla Reginatto , Voyceik Ricardo , Santos de Mattos Letícia Graziela Costa , Kulik Mariane Gonçalves , Camargo Josué Oliveira , Repula de Oliveira Aryel Marlus , de Lima Nichio Bruno Thiago , Marchaukoski Jeroniza Nunes , da Silva Filho Antonio Camilo , Guizelini Dieval , Ortega J. Miguel , Pedrosa Fabio O. , Raittz Roberto Tadeu
Published: January 2020

Vectoral and alignment-free approaches to biological sequence representation have been explored in bioinformatics to efficiently handle big data. Even so, most current methods involve sequence comparisons via alignment-based heuristics and fail when applied to the analysis of large data sets. Here, we present “Spaced Words Projection (SWeeP)”, a method for representing biological sequences using relatively small vectors while preserving intersequence comparability. SWeeP uses spaced-words by scanning the sequences and generating indices to create a higher-dimensional vector that is later projected onto a smaller randomly oriented orthonormal base. We constructed phylogenetic trees for all organisms with mitochondrial and bacterial protein data in the NCBI database. SWeeP quickly built complete and accurate trees for these organisms with low computational cost. We compared SWeeP to other alignment-free methods and Sweep was 10 to 100 times quicker than the other techniques. A tool to build SWeeP vectors is available at https://sourceforge.net/projects/spacedwordsprojection/.
Shortening injection matrix for serial crystallography
Authors: Nam Ki Hyun
Published: January 2020

Serial crystallography allows crystal structures to be determined at room temperature through the steady delivery of crystals to the X-ray interaction point. Viscous delivery media are advantageous because they afford efficient sample delivery from an injector or syringe at a low flow rate. Hydrophobic delivery media, such as lipidic cubic phase (LCP) or grease, provide a stable injection stream and are widely used. The development of new hydrophobic delivery materials can expand opportunities for future SX studies with various samples. Here, I introduce fat-based shortening as a delivery medium for SX experiments. This material is commercially available at low cost and is straightforward to handle because its phase (i.e., solid or liquid) can be controlled by temperature. Shortening was extruded from a syringe needle in a stable injection stream even below 200 nl/min. X-ray exposed shortening produced several background scattering rings, which have similar or lower intensities than those of LCP and contribute negligibly to data processing. Serial millisecond crystallography was performed using two shortening delivery media, and the room temperature crystal structures of lysozyme and glucose isomerase were successfully determined at resolutions of 1.5–2.0 Å. Therefore, shortening can be used as a sample delivery medium in SX experiments.
γ-AApeptides–based Small Molecule Ligands That Disaggregate Human Islet Amyloid Polypeptide
Authors: Bolarinwa Olapeju , Li Chunpu , Khadka Nawal , Li Qi , Wang Yan , Pan Jianjun , Cai Jianfeng
Published: January 2020

The abnormal folding and aggregation of functional proteins into amyloid is a typical feature of many age-related diseases, including Type II diabetes. Growing evidence has revealed that the prevention of aggregate formation in culprit proteins could retard the progression of amyloid diseases. Human Amylin, also known as human islet amyloid polypeptide (hIAPP), is the major factor for categorizing Type II diabetes as an amyloid disease. Specifically, hIAPP has a great aggregation potential, which always results in a lethal situation for the pancreas. Many peptide inhibitors have been constructed from the various segments of the full-length hIAPP peptide; however, only a few have their origin from the screening of combinatorial peptidomimetic library. In this study, based on HW-155, which was previously discovered from a one–bead–one compound (OBOC) library to inhibit Aβ40 aggregation, we investigated eight (8) analogues and evaluated their amyloid-prevention capabilities for inhibiting fibrillization of hIAPP. Characterization studies revealed that all analogues of HW-155, as well as HW-155, were effective inhibitors of the fibril formation by hIAPP.
Modeling of the irradiation effect on some physicochemical properties of metoprolol tartrate for safe medical uses
Authors: Ouerfelli Najoua , Vrinceanu Narcisa , Mliki Ezzedine , Homeida Abdelgadir M. , Amin Kamal A. , Ogrodowczyk Magdalena , Alshehri Fawziah S. , Ouerfelli Noureddine
Published: January 2020

The effect of gamma-irradiation and ionizing radiation (high-energy electrons beam) on the physicochemical properties of metoprolol tartrate at the solid phase and aqueous solution, has been investigated in the present study to model some properties affected by absorbed doses and to reveal some interesting mutual causal correlation. The proposed some interesting models can be adapted to other experimental conditions, and the newly obtained values of the adjustable parameters could be an excellent criterion of the state quality of the metoprolol tartrate or for other additional interpretations. The peculiar behaviour of variation of physicochemical properties against dose leads us to confirm the suggested optimized doses mentioned in previous work, for sterilization and safe medical uses.
Geochemistry and tectonic significance of late Paleoproterozoic A-type granites along the southern margin of the North China Craton
Authors: Wang Yan , Yang Yi-Zeng , Siebel Wolfgang , Zhang He , Zhang Yuan-Shuo , Chen Fukun
Published: January 2020

The Longwangzhuang pluton is a typical example of Paleoproterozoic A-type granite intrusions at the southern margin of the North China Craton. This pluton is composed of arfvedsonite granite and minor aegirine–augite granites. Samples from both granite types display similar zircon U-Pb ages with 207U-206Pb ages of 1612 ± 19 Ma [mean square weighted deviation (MSWD) = 0.66] and 1609 ± 24 Ma (MSWD = 0.5), respectively. The granites exhibit similar high silica (SiO2 = 71.1–73.4 wt.%), high alkaline (Na2O + K2O = 8.10–9.26 wt.%, K2O/Na2O > 1), and low Al2O3 (11.8–12.8 wt. %) contents and metaluminous to weakly peraluminous bulk chemistry. The chemical variations of the Longwangzhuang pluton suggest the effects of mineral fractionation. In addition, all samples show typical characteristics of A-type granites, such as high 10000Ga/Al ratios (4.10–7.28), high FeOtot/(FeOtot + MgO) ratios (0.88–0.99), and high Zr (484–1082 ppm), Ce (201–560 ppm), and Y (78–156 ppm) contents. The εNd(t) values and the (206Pb/204Pb)t, (207Pb/204Pb)t, and (208Pb/204Pb)t ratios of the arfvedsonite granite samples vary from −4.6 to –5.3, 15.021 to 17.349, 15.241 to 15.472, and 33.206 to 36.905, respectively, and those for the aegirine–augite granite sample amount at −0.2, 14.421, 15.175, and 33.706. The distinct and variable Nd and Pb isotope values indicate the presence of heterogeneous protoliths. Based on its geochemistry, its low initial Pb isotope ratios, and its enrichment in Nd isotopes, we infer that the Longwangzhuang A-type granite is the partial melting product of basement rocks such as the Taihua Group gneisses accompanied by some involvement of juvenile material from the mantle. Together with published data from other Paleoproterozoic A-type granite plutons exposed at the southern margin of the craton, our findings suggest that these granites had a similar origin. Furthermore, geochemically, they can be divided into two groups: A2-type, which formed earlier (~1.8–1.6 Ga), and A1-type, which formed later (~1.6–1.5 Ga). Combining this information with the variations in whole-rock Nd and zircon Hf isotopic composition at ca. 1.6 Ga, we propose that tectonic transformation from post-orogenic to anorogenic magmatism occurred at the southern margin of the North China Craton at that time.
Group task-related component analysis (gTRCA): a multivariate method for inter-trial reproducibility and inter-subject similarity maximization for EEG data analysis
Authors: Tanaka Hirokazu
Published: January 2020

EEG is known to contain considerable inter-trial and inter-subject variability, which poses a challenge in any group-level EEG analyses. A true experimental effect must be reproducible even with variabilities in trials, sessions, and subjects. Extracting components that are reproducible across trials and subjects benefits both understanding common mechanisms in neural processing of cognitive functions and building robust brain-computer interfaces. This study extends our previous method (task-related component analysis, TRCA) by maximizing not only trial-by-trial reproducibility within single subjects but also similarity across a group of subjects, hence referred to as group TRCA (gTRCA). The problem of maximizing reproducibility of time series across trials and subjects is formulated as a generalized eigenvalue problem. We applied gTRCA to EEG data recorded from 35 subjects during a steady-state visual-evoked potential (SSVEP) experiment. The results revealed: (1) The group-representative data computed by gTRCA showed higher and consistent spectral peaks than other conventional methods; (2) Scalp maps obtained by gTRCA showed estimated source locations consistently within the occipital lobe; And (3) the high-dimensional features extracted by gTRCA are consistently mapped to a low-dimensional space. We conclude that gTRCA offers a framework for group-level EEG data analysis and brain-computer interfaces alternative in complement to grand averaging.
In vivo analysis of FANCD2 recruitment at meiotic DNA breaks in Caenorhabditis elegans
Authors: Germoglio Marcello , Valenti Anna , Gallo Ines , Forenza Chiara , Santonicola Pamela , Silva Nicola , Adamo Adele
Published: January 2020

Fanconi Anemia is a rare genetic disease associated with DNA repair defects, congenital abnormalities and infertility. Most of FA pathway is evolutionary conserved, allowing dissection and mechanistic studies in simpler model systems such as Caenorhabditis elegans. In the present study, we employed C. elegans to better understand the role of FA group D2 (FANCD2) protein in vivo, a key player in promoting genome stability. We report that localization of FCD-2/FANCD2 is dynamic during meiotic prophase I and requires its heterodimeric partner FNCI-1/FANCI. Strikingly, we found that FCD-2 recruitment depends on SPO-11-induced double-strand breaks (DSBs) but not RAD-51-mediated strand invasion. Furthermore, exposure to DNA damage-inducing agents boosts FCD-2 recruitment on the chromatin. Finally, analysis of genetic interaction between FCD-2 and BRC-1 (the C. elegans orthologue of mammalian BRCA1) supports a role for these proteins in different DSB repair pathways. Collectively, we showed a direct involvement of FCD-2 at DSBs and speculate on its function in driving meiotic DNA repair.
Methods to probe the formation of biofilms: applications in foods and related surfaces
Authors: Huang Yating , Chakraborty Sayak , Liang Hong
Published: January 2020

Biofilms of bacteria affect product quality and safety of food.
Assessment of ATR-FTIR spectroscopy with multivariate analysis to investigate the binding mechanisms of Ag and TiO2 nanoparticles to Chelex®-100 or Metsorb™ for the DGT technique
Authors: Pouran Hamid , Perez Colodrero Rosario , Wu Shuang , Hix Gary , Zakharova Julia , Zhang Hao
Published: January 2020

A major challenge in studying nanomaterials' ecotoxicology is lack of reliable techniques to measure available concentrations of these materials in the environment.