bluuebunny/crossref_metadata_2025 huggingface dataset:
Integral performance optimization for the two-stage-to-orbit RBCC-RKT launch vehicle based on GPM
Authors: Zhang L. , Sun M. , Cheng Q. , Chen Z. , Zhang X.
Published: June 2019

The takeoff-mass of a two-stage-to-orbit Rocket-Based Combined Cycle Engine-Rocket (RBCC-RKT) launch vehicle is a crucial factor in its comprehensive performance. This paper optimizes the takeoff-mass together with the trajectory by reformulating it to a nonlinear optimal control problem. The range of the second stage rocket mass is considered as a process constraint. When the scopes of initial and terminal states are specified, the problem can be solved by using the Gauss pseudo-spectral method (GPM). In order to reduce the convergent difficulty caused by using table data, the data in different stages are utilized by employing an integrated interpolation strategy through the optimization. Simulation results show that the mass can be effectively optimized to meet the inertia mass ratio constraint of the first-stage, and the separation of Mach number and altitude can be optimized at the same time.
The effects of increased acetate turnover on glucose-induced insulin secretion in lean and obese humans
Authors: Petersen Kitt Falk , Impellizeri Anne , Cline Gary W. , Shulman Gerald I.
Published: June 2019

Introduction:

Increased endogenous acetate production (Ra) in rodents has been shown to activate the parasympathetic nervous system and thereby promote increased glucose-stimulated insulin secretion (GSIS), increased ghrelin secretion, hyperphagia and obesity.

Aim:

To examine whether rates of acetate turnover are different in lean versus obese humans and whether increased acetate turnover promotes increased GSIS and increased ghrelin secretion in humans.

Methods:

Basal acetate Ra was measured following an overnight fast in lean (BMI: 21.3 ± 1.1 Kg/m2) and obese (30.2 ± 0.9 Kg/m2, P = 0.00001) individuals. The subjects underwent two hyperglycemic (10 mmol/L) clamp studies to measure GSIS during a basal acetate infusion and during a high-dose acetate infusion increasing plasma acetate concentrations ∼5-fold.

Results:

Basal acetate Ra was 30% higher in the lean compared to the obese subjects (257 ± 27 vs. 173 ± 18 μmol/min; P = 0.025). Basal plasma insulin concentrations were 4-fold higher in the obese than the lean subjects (P = 0.008) and increased 5-fold during hyperglycemia in both groups, independent of changes in plasma acetate concentrations. Fasting plasma ghrelin concentrations were 35% lower in the obese compared to the lean subjects (P = 0.015). During the hyperglycemic clamp, plasma ghrelin decreased by 42% in the lean group (P < 0.022 vs. basal) and did not change in the obese group.

Conclusion:

Rates of endogenous acetate turnover are ∼30% higher in the lean subjects compared to the obese subjects, and increasing plasma acetate turnover does not promote increased GSIS or ghrelin secretion in either group.
Cell wall dynamics under conditions of diffuse growth in the thick-walled cortical tissue (prosoplectenchyma) of Ramalina usnea
Authors: SANDERS William B. , DE LOS RÍOS Asunción
Published: June 2019

A recent field study indicated that thalli of the beard lichen Ramalina usnea undergo diffuse (“intercalary”) growth throughout their length. We examined thallus sections with TEM to better understand how the highly thickened cell walls of the prosoplectenchymatous cortex behave under conditions of continued expansion. Cell protoplasts were surrounded by massive accumulations of structured electron-dense wall layers interspersed with amorphous, electron-transparent substances, visible as concentric rings in transverse section. Nearest the protoplast, electron-dense wall layers were distinct and more or less alternated with irregular deposits of electron-transparent material. With increasing distance from the protoplast, the electron-dense wall layers were increasingly disrupted and intermixed among the electron-transparent materials. New cell branches grew through the accumulated wall materials, interrupting the layers they penetrated while producing their own concentric wall layers. The differing amounts of cell wall material accumulated was further indication of the different relative ages of such neighbouring cells. These observations suggest that cell walls are disrupted by diffuse tissue expansion and continually replaced by new walls and wall materials deposited to their interior at the interface with the protoplast. This pattern of development, documented previously in R. menziesii and U. longissima, suggests that component cells of lichen prosoplectenchyma behave quite differently from those of diffusely expanding filaments studied in non-lichen-forming fungi, where a single, discrete cell wall is maintained throughout growth.
Semantics of higher inductive types
Authors: LUMSDAINE PETER LEFANU , SHULMAN MICHAEL
Published: June 2019

Higher inductive typesare a class of type-forming rules, introduced to provide basic (and not-so-basic) homotopy-theoretic constructions in a type-theoretic style. They have proven very fruitful for the “synthetic” development of homotopy theory within type theory, as well as in formalising ordinary set-level mathematics in type theory. In this paper, we construct models of a wide range of higher inductive types in a fairly wide range of settings.

We introduce the notion ofcell monad with parameters: a semantically-defined scheme for specifying homotopically well-behaved notions of structure. We then show that any suitable model category hasweakly stable typal initial algebrasfor any cell monad with parameters. When combined with the local universes construction to obtain strict stability, this specialises to give models of specific higher inductive types, including spheres, the torus, pushout types, truncations, the James construction and general localisations.

Our results apply in any sufficiently nice Quillen model category, including any right proper, simplicially locally cartesian closed, simplicial Cisinski model category (such as simplicial sets) and any locally presentable locally cartesian closed category (such as sets) with its trivial model structure. In particular, any locally presentable locally cartesian closed (∞, 1)-category is presented by some model category to which our results apply.
Equity for Women and Marginalized Groups in Patriarchal Societies during Forest Landscape Restoration: The Controlling Influence of Tradition and Culture
Authors: Baynes Jack , Herbohn John , Gregorio Nestor , Unsworth William , Tremblay Émilie Houde
Published: June 2019

We explore the difficulty of achieving equity for women in two forest and livelihood restoration (FLR) pilot projects, one each in Papua New Guinea (PNG) and the Philippines. We use institutional bricolage as a framework to explain the context and background of stakeholders’ decision-making and the consequent impact on equity and benefit distribution. In the Philippines, material and institutional support was initially successful in assisting participants to establish small-scale tree plantations. A structured approach to institutional development has successfully evolved to meet the needs of women, even though corruption has re-emerged as a destabilizing influence. In PNG, despite success in establishing trees and crops, the participation of women was subjugated to traditional customs and norms that precluded them from engaging in land management decisions. The capacity-building and gender-equity principles of FLR consequently became compromised. We conclude that in some patriarchal societies achieving equity for women will be difficult and progress will be contingent on a detailed understanding of the effects of traditional customs and norms on participation and decision-making.
Temporal changes in left ventricular strain with the development of rejection in paediatric heart transplant recipients
Authors: Godown Justin , McEachern William A. , Dodd Debra A. , Stanley Michael , Havens Corey , Xu Meng , Slaughter James C. , Bearl David W. , Soslow Jonathan H.
Published: June 2019

Introduction:

Myocardial strain measurements are increasingly used to detect complications following heart transplantation. However, the temporal association of these changes with allograft rejection is not well defined. The aim of this study was to describe the evolution of strain measurements prior to the diagnosis of rejection in paediatric heart transplant recipients.

Methods:

All paediatric heart transplant recipients (2004–2015) with at least one episode of acute rejection were identified. Longitudinal and circumferential strain measurements were assessed at the time of rejection and retrospectively on all echocardiograms until the most recent negative biopsy. Smoothing technique (LOESS) was used to visualise the changes of each variable over time and estimate the time preceding rejection at which alterations are first detectable.

Results:

A total of 58 rejection episodes were included from 37 unique patients. In the presence of rejection, there were decrements from baseline in global longitudinal strain (−18.2 versus −14.1), global circumferential strain (−24.1 versus −19.6), longitudinal strain rate (−1 versus −0.8), circumferential strain rate (−1.3 versus −1.1), peak longitudinal early diastolic strain rate (1.3 versus 1), and peak circumferential early diastolic strain rate (1.5 versus 1.3) (p<0.01 for all). The earliest detectable changes occurred 45 days prior to rejection with simultaneous alterations in myocardial strain and ejection fraction.

Conclusions:

Changes in graft function can be detected non-invasively prior to the diagnosis of rejection. However, changes in strain occur concurrently with a decline in ejection fraction. Strain measurements aid in the non-invasive detection of rejection, but may not facilitate earlier diagnosis compared to more traditional measures of ventricular function.
Assisted dying in the terminally ill: an evaluation of views on euthanasia
Authors: Duxbury Sophie
Published: June 2019

Introduction:

The purpose of this study was to evaluate views and attitudes concerning the legality of assisted death and euthanasia in the UK and to identify the circumstances in which individuals would or would not consider assisted death.

Materials and methods:

The views of a sample of the general population in the UK were sought through the use of a mixed methods questionnaire open to the public for 3 weeks.

Results:

The responses of 117 participants were analysed using an SPSS MANOVA statistical test for quantitative data and an in-depth content coding analysis for qualitative responses.

Discussion:

The majority of respondents, 85·5%, believed that Physician-Assisted Death (PAD) should be legalised in the UK and that individuals should be able to choose when, 88%, and where, 88·9%, they die. Qualitative analysis revealed that more people would consider a PAD for a severe physical terminal illness over mental illness. There was no statistical significance for variables for quantitative data when considering overall demographics, professional and educational backgrounds of the respondents.

Conclusion:

The majority of respondents in this study indicated that they believe assisted suicide should be made legal and that the option should be available for those who are terminally ill. Views indicated that if assisted dying was legal, it would allow terminally ill patients to die with dignity and without prolonging pain.
The costs of interest representation – a resource perspective on informational lobbying
Authors: Flöthe Linda
Published: June 2019

While expert information and information on public preferences are seen as key resources that interest groups provide to policymakers, little is known about the resources that are necessary to acquire such information. Existing scholarship argues that financial resources enhance a group’s ability to supply information, which could be problematic as it suggests that resource poor groups are disadvantaged when lobbying policymakers. Applying a resource perspective to informational lobbying, this paper argues that different information types require different resources and that financial means are less important than assumed. The predictions are tested using a new dataset and survey of 383 advocates active on 50 specific policy issues in five West European countries. The results show that while economic resources are indeed associated with a higher amount of expert information, political capacities allow a group to provide both expert information and information on public preferences. This suggests that groups can rely on other than economic resources for information provision.
Profiles of gene expression in maternal blood predict offspring birth weight in normal pregnancy
Authors: McDade Thomas W. , Kuzawa Chris W. , Borja Judith , Arevalo Jesusa M. G. , Miller Greg , Cole Steve W.
Published: June 2019

The association between lower birth weight and increased disease risk in adulthood has drawn attention to the physiological processes that shape the gestational environment. We implement genome-wide transcriptional profiling of maternal blood samples to identify subsets of genes and associated transcription control pathways that predict offspring birth weight. Female participants (N = 178, mean = 27.0 years) in a prospective observational birth cohort study were contacted between 2009 and 2014 to identify new pregnancies. An in-home interview was scheduled for early in the third trimester (mean = 30.3 weeks) to collect pregnancy-related information and a blood sample, and birth weight was measured shortly after delivery. Transcriptional activity in white blood cells was determined with a whole-genome gene expression direct hybridization assay. Fifty transcripts were differentially expressed in association with offspring birth weight, with 18 up-regulated in relation to lower birth weight, and 32 down-regulated. Examination of transcription control pathways identified increased activity of NF-κB, AP-1, EGR1, EGR4, and Gfi families, and reduced the activity of CEBP, in association with lower birth weight. Transcript origin analyses identified non-classical CD16+ monocytes, CD1c+ myeloid dendritic cells, and neutrophils as the primary cellular mediators of differential gene expression. These results point toward a systematic regulatory shift in maternal white blood cell activity in association with lower offspring birth weight, and they suggest that analyses of gene expression during gestation may provide insight into regulatory and cellular mechanisms that influence birth outcomes.
Political Competition, Partisanship, and Interpersonal Trust Under Party Dominance: Evidence from Post-Apartheid South Africa
Authors: Carlin Ryan E. , Love Gregory J. , Young Daniel J.
Published: June 2019

How does single-party dominance influence interpersonal trust? We draw on evidence from trust games played by more than 2,000 subjects in South Africa, where, since Apartheid, race-based social enmity has persisted under democratic competition characterized by single-party dominance. We find that partisan-based trust discrimination is most pronounced for those who identify with the main opposition party and is driven by strong distrust of rival partisans. These findings underscore how electoral competition, in general, shapes trust across party lines and suggests one-sided competition, in particular, has asymmetrical effects between parties in dominant party systems. Moreover, this study provides additional evidence regarding the relative weights of trustworthiness stereotypes tied to partisanship and race.
Sensitivity of the Near‐Shore Oceanic Circulation Off Central Chile to Coastal Wind Profiles Characteristics
Authors: Astudillo O. , Dewitte B. , Mallet M. , Rutllant J. A. , Goubanova K. , Frappart F. , Ramos M. , Bravo L.
Published: June 2019

In Eastern Boundary Upwelling Systems (EBUS), the upwelling favorable wind speeds decrease toward the coast in the so‐called wind drop‐off coastal strip, which has been shown to be influential on the coastal upwelling dynamics, particularly in terms of the relative contributions of Ekman drift and Ekman suction to coastal upwelling. Currently, the wind drop‐off length scale is not properly resolved by the atmospheric forcing of regional ocean models in EBUS, featuring a smoother cross‐shore wind profile that results in stronger near‐shore speeds that could partly explain the coastal cold bias often found in those model simulations. Here, as a case study for the upwelling system off Central Chile, the sensitivity of upwelling dynamics to the coastal wind reduction is investigated using a Regional Ocean Modeling System (ROMS). Coastal wind profiles at different resolutions are first generated using a regional atmospheric model, validated from altimeter data, and then used to correct the coarse atmospheric wind forcing used for sensitivity experiments with ROMS. It is shown that the wind drop‐off correction induces a reduction in the oceanic coastal jet intensity, a stronger poleward undercurrent and a coherent offshore Ekman drift. It also yields a significant reduction of the cold bias along the coast compared to the simulation with “uncorrected” winds. Such reduction cannot be solely explained by the reduced Ekman transport only partially compensated by increase in Ekman suction. The analysis of the surface heat budget reveals in fact that an important contributor to the cooling reduction along the coast in the presence of coastal wind drop‐off is the heat flux term mediated by the reduction in the mixed‐layer depth. Overall, our results illustrate the nonlinear response of the upwelling dynamics to the coastal wind profiles in this region.
Spatial and Temporal Analysis of Precipitation Extremities of Eastern Nepal in the Last Two Decades (1997–2016)
Authors: Subba Sunil , Ma Yaoming , Ma Weiqiang
Published: June 2019

In recent days there have been discussions regarding the impact of climate change and its vagaries of the weather, particularly concerning extreme events. Nepal, being a mountainous country, is more susceptible to precipitation extreme events and related hazards, which hinder the socioeconomic development of the nation. In this regard, this study aimed to address this phenomenon for one of the most naturally and socioeconomically important regions of Nepal, namely, Eastern Nepal. The data were collected for the period of 1997 to 2016. The interdecadal comparison for two periods (1997–2006 and 2007–2016) was maintained for the calculation of extreme precipitation indices as per recommended by Expert Team on Climate Change Detection and Indices. Linear trends were calculated by using Mann‐Kendall and Sen's Slope estimator. The average annual precipitation was found to be decreasing at an alarming rate of −20 mm/year in the last two decades' tenure. In case of extreme precipitation events, consecutive dry days, one of the frequency indices, showed a solo increase in its trend (mostly significant). Meanwhile, all the intensity indices of extreme precipitation showed decreasing trends (mostly insignificant). Thus, it can be concluded that Eastern Nepal has witnessed some significant drier days in the last two decades, as the events of heavy, very heavy, extremely heavy precipitation events, and annual wet day precipitation (PRCPTOT) were found to be decreasing. The same phenomena were also seen in the Tropical Rainfall Measuring Mission 3B42 V7 satellite precipitation product for whole Nepal.
Pentraxin 3 deficiency exacerbates lipopolysaccharide-induced inflammation in adipose tissue
Authors: Guo Hong , Qiu Xiaoxue , Deis Jessica , Lin Te-Yueh , Chen Xiaoli
Published: June 2019

Background/objectives

Pentraxin 3 (PTX3) has been characterized as a soluble and multifunctional pattern recognition protein in the regulation of innate immune response. However, little is known about its role in adipose tissue inflammation and obesity. Herein, we investigated the role of PTX3 in the regulation of lipopolysaccharide (LPS)-induced inflammation in adipocytes and adipose tissue, as well as high-fat diet (HFD)-induced metabolic inflammation in obesity.

Methods

Ptx3 knockdown 3T3-L1 Cells were generated using shRNA for Ptx3 gene and treated with different inflammatory stimuli. For the in vivo studies, Ptx3 knockout mice were treated with 0.3 mg/kg of LPS for 6 h. Adipose tissues were collected for gene and protein expression by qPCR and western blotting, respectively. Ptx3 knockout mice were fed with HFD for 12 week since 6 week of age.

Results

We observed that the expression of PTX3 in adipose tissue and serum PTX3 were markedly increased in response to LPS administration. Knocking down Ptx3 in 3T3-L1 cells reduced adipogenesis and caused a more profound and sustained upregulation of proinflammatory gene expression and signaling pathway activation during LPS-stimulated inflammation in 3T3-L1 adipocytes. In vivo studies showed that PTX3 deficiency significantly exacerbated the LPS-induced upregulation of inflammatory genes and downregulation of adipogeneic genes in visceral and subcutaneous adipose tissue of mice. Accordingly, LPS stimulation elicited increased activation of nuclear factor-κB (NF-κB) and p44/42 MAPK (Erk1/2) signaling pathways in visceral and subcutaneous adipose tissue. The expression of PTX3 in adipose tissue was also induced by HFD, and PTX3 deficiency led to the upregulation of proinflammatory genes in visceral adipose tissue of HFD-induced obese mice.

Conclusions

Our results suggest a protective role of PTX3 in LPS- and HFD-induced sustained inflammation in adipose tissue.
A mass-customizable dermal patch with discrete colorimetric indicators for personalized sweat rate quantification
Authors: Jain Vaibhav , Ochoa Manuel , Jiang Hongjie , Rahimi Rahim , Ziaie Babak
Published: June 2019

In this paper, we present a disposable, colorimetric, user-friendly and mass-customizable dermal patch for chronological collection and discrete real-time in situ measurement of sweat secretion over a small area of skin. The patch consists of a laminated filter paper patterned into radially arranged channels/fingers with water-activated dyes at their tips. As channels are filled during perspiration, their tips change color once fully saturated, providing easily identifiable levels of water loss which in turn can be mapped to personal dehydration levels. The patch can be manufactured at low cost in a variety of sizes to allow hydration monitoring for individuals participating in activities under different conditions (intensity, temperature, humidity, etc.). Furthermore, we describe an analytical model that enables mass customization of such a flexible wearable system accommodating a broad range of sweat rates and volumes to generate patch designs that are personalized to an individual’s sweat rate, desired time of usage, and the temporal resolution of the required feedback. As a proof-of-concept demonstration, we characterized laser-fabricated patches that cover (7 cm × 5 cm) area of skin having various wicking materials, thicknesses (180–540 µm), and pore sizes (3–11 µm). Tests were conducted at various flow rates simulating different sweating intensities in the range of 1.5–15 mg/cm2/min. Experimental results for the case of a half-marathon runner targeting 90 min of usage and sweating at a rate of 1.5 mg/cm2/min indicated measurement accuracy of 98.3% when the patch is completely filled.
Finding the optical properties of plasmonic structures by image processing using a combination of convolutional neural networks and recurrent neural networks
Authors: Sajedian Iman , Kim Jeonghyun , Rho Junsuk
Published: June 2019

Image processing can be used to extract meaningful optical results from images. Here, from images of plasmonic structures, we combined convolutional neural networks with recurrent neural networks to extract the absorption spectra of structures. To provide the data required for the model, we performed 100,000 simulations with similar setups and random structures. In designing this deep network, we created a model that can predict the absorption response of any structure with a similar setup. We used convolutional neural networks to collect spatial information from the images, and then, we used that data and recurrent neural networks to teach the model to predict the relationship between the spatial information and the absorption spectrum. Our results show that this image processing method is accurate and can be used to replace time- and computationally-intensive numerical simulations. The trained model can predict the optical results in less than a second without the need for a strong computing system. This technique can be easily extended to cover different structures and extract any other optical properties.
Targeting the cell cycle in head and neck cancer by Chk1 inhibition: a novel concept of bimodal cell death
Authors: van Harten Anne M. , Buijze Marijke , van der Mast Richard , Rooimans Martin A. , Martens-de Kemp Sanne R. , Bachas Costa , Brink Arjen , Stigter-van Walsum Marijke , Wolthuis Rob M. F. , Brakenhoff Ruud H.
Published: June 2019

Head and neck squamous cell carcinomas (HNSCCs) coincide with poor survival rates. The lack of driver oncogenes complicates the development of targeted treatments for HNSCC. Here, we follow-up on two previous genome-wide RNA and microRNA interference screens in HNSCC to cross-examine tumor-specific lethality by targeting ATM, ATR, CHEK1, or CHEK2. Our results uncover CHEK1 as the most promising target for HNSCC. CHEK1 expression is essential across a panel of HNSCC cell lines but redundant for growth and survival of untransformed oral keratinocytes and fibroblasts. LY2603618 (Rabusertib), which specifically targets Chk1 kinase, kills HNSCC cells effectively and specifically. Our findings show that HNSCC cells depend on Chk1-mediated signaling to progress through S-phase successfully. Chk1 inhibition coincides with stalled DNA replication, replication fork collapses, and accumulation of DNA damage. We further show that Chk1 inhibition leads to bimodal HNSCC cell killing. In the most sensitive cell lines, apoptosis is induced in S-phase, whereas more resistant cell lines manage to bypass replication-associated apoptosis, but accumulate chromosomal breaks that become lethal in subsequent mitosis. Interestingly, CDK1 expression correlates with treatment outcome. Moreover, sensitivity to Chk1 inhibition requires functional CDK1 and CDK4/6 to drive cell cycle progression, arguing against combining Chk1 inhibitors with CDK inhibitors. In contrast, Wee1 inhibitor Adavosertib progresses the cell cycle and thereby increases lethality to Chk1 inhibition in HNSCC cell lines. We conclude that Chk1 has become a key molecule in HNSCC cell cycle regulation and a very promising therapeutic target. Chk1 inhibition leads to S-phase apoptosis or death in mitosis. We provide a potential efficacy biomarker and combination therapy to follow-up in clinical setting.
Immunoglobulin gene rearrangement IGHV3-48 is a predictive marker of histological transformation into aggressive lymphoma in follicular lymphomas
Authors: García-Álvarez María , Alonso-Álvarez Sara , Prieto-Conde Isabel , Jiménez Cristina , Sarasquete M. Eugenia , Chillón M. Carmen , Medina Alejandro , Balanzategui Ana , Maldonado Rebeca , Antón Alicia , Puig Noemí , Rodríguez Marta , Blanco Oscar , Tamayo Pilar , González-Calle Verónica , Martín Alejandro , García-Sanz Ramón , González Marcos , Caballero M. Dolores , Alcoceba Miguel
Published: June 2019

Follicular lymphoma (FL) is a heterogeneous disease whose pathogenesis remains partially unknown. Around 20% of FL patients experience early progression or treatment-refractory disease and 2–3% of patients per year experience histological transformation (HT) into a more aggressive lymphoma (tFL). Here, we evaluate the immunoglobulin heavy chain variable (IGHV) gene usage and mutational status in 187 FL cases to assess its impact on clinical outcome and histological transformation. The IGHV gene repertoire was remarkably biased in FL. The IGHV4-34 (14%), IGHV3-23 (14%), IGHV3-48 (10%), IGHV3-30 (9%) and IGHV3-21 (7%) genes accounted for more than half of the whole cohort. IGHV3-48 was overrepresented in cases of tFL (19%) compared with non-transformed FL at 5 years (5%, P = 0.05). Patients with the IGHV3-48 gene were significantly more likely to have had HT after 10 years than those who used other genes (71% vs. 25%, P < 0.05), irrespective of the therapy they received. Moreover, IGHV3-30 was also overrepresented in cases of FL (9%) and tFL (13%) compared with diffuse large B-cell lymphoma in which it was nearly absent. In conclusion, our results indicate a role for antigen selection in the development of FL, while the use of IGHV3-48 could help predict histological transformation.
Exosomes from CD99-deprived Ewing sarcoma cells reverse tumor malignancy by inhibiting cell migration and promoting neural differentiation
Authors: De Feo Alessandra , Sciandra Marika , Ferracin Manuela , Felicetti Federica , Astolfi Annalisa , Pignochino Ymera , Picci Piero , Carè Alessandra , Scotlandi Katia
Published: June 2019

Ewing sarcoma (EWS) is an aggressive mesenchymal tumor with unmet clinical need and significant social impacts on children, adolescents, and young adults. CD99, a hallmark surface molecule of EWS, participates in crucial biological processes including cell migration, differentiation, and death. EWS cells can release CD99 through exosomes (EXOs), specialized extracellular vesicles with major cell communication roles. Here we show that, as a consequence of CD99 silencing, EWS cells deliver exosomes with oncosuppressive functions that significantly reduce tumor aggressiveness. These CD99-lacking microvesicles modulate gene expression of the EWS-recipient cells, reduce proliferation and migration, in turn inducing a more-differentiated less-malignant phenotype. The most relevant effects were detected on the activator protein-1 signaling pathway whose regulation was found to be dependent on the specific cargo loaded in vesicles after CD99 shutdown. Investigation of the miRNA content of CD99-deprived EXOs identified miR-199a-3p as a key driver able to reverse EWS malignancy in experimental models as well as in clinical specimens. All together, our data provide evidence that the abrogation of CD99 in EWS tumor cells leads to produce and release EXOs capable to transfer their antineoplastic effects into the nearby tumor cells, suggesting a novel atypical role for these microvesicles in reversion of malignancy rather than in priming the soil for progression and metastatic seeding. This conceptually innovative approach might offer a new therapeutic opportunity to treat a tumor still refractory to most treatments.
Perturbation of synapsins homeostasis through HIV-1 Tat-mediated suppression of BAG3 in primary neuronal cells
Authors: Mohseni Ahooyi Taha , Torkzaban Bahareh , Shekarabi Masoud , Tahrir Farzaneh G. , Decoppet Emilie A. , Cotto Bianca , Langford Dianne , Amini Shohreh , Khalili Kamel
Published: June 2019

HIV-1 Tat is known to be released by HIV infected non-neuronal cells in the brain, and after entering neurons, compromises brain homeostasis by impairing pro-survival pathways, thus contributing to the development of HIV-associated CNS disorders commonly observed in individuals living with HIV. Here, we demonstrate that synapsins, phosphoproteins that are predominantly expressed in neuronal cells and play a vital role in modulating neurotransmitter release at the pre-synaptic terminal, and neuronal differentiation become targets for Tat through autophagy and protein quality control pathways. We demonstrate that the presence of Tat in neurons results in downregulation of BAG3, a co-chaperone for heat shock proteins (Hsp70/Hsc70) that is implicated in protein quality control (PQC) processes by eliminating mis-folded and damaged proteins, and selective macroautophagy. Our results show that treatment of cells with Tat or suppression of BAG3 expression by siRNA in neuronal cells disturbs subcellular distribution of synapsins and synaptotagmin 1 (Syt1) leading to their accumulation in the neuronal soma and along axons in a punctate pattern, rather than being properly distributed at axon-terminals. Further, our results revealed that synapsins partially lost their stability and their removal via lysosomal autophagy was noticeably impaired in cells with low levels of BAG3. The observed impairment of lysosomal autophagy, under this condition, is likely caused by cells losing their ability to process LC3-I to LC3-II, in part due to a decrease in the ATG5 levels upon BAG3 knockdown. These observations ascribe a new function for BAG3 in controlling synaptic communications and illuminate a new downstream target for Tat to elicit its pathogenic effect in impacting neuronal cell function and behavior.
Author Correction: Sustained NF-κB-STAT3 signaling promotes resistance to Smac mimetics in Glioma stem-like cells but creates a vulnerability to EZH2 inhibition
Authors: da Hora Cintia Carla , Pinkham Kelsey , Carvalho Litia , Zinter Max , Tabet Elie , Nakano Ichiro , Tannous Bakhos A. , Badr Christian E.
Published: June 2019

After publication of this article, the authors realized that the Supplementary Figure S5B had an error in it. Specifically, the labels for BIR and AXD1480 on the x-axis were in the wrong place. All text referring to the figure, including the legend, are correct and this does not impact the findings of the study. This error has not been corrected in the original version of the Article.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
A six-inhibitor culture medium for improving naïve-type pluripotency of porcine pluripotent stem cells
Authors: Yuan Ye , Park Jinkyu , Tian Yuchen , Choi Jungmin , Pasquariello Rolando , Alexenko Andrei P. , Dai Aihua , Behura Susanta K. , Roberts R. Michael , Ezashi Toshihiko
Published: June 2019

Understanding essential signaling network requirements and making appropriate adjustments in culture conditions are crucial if porcine pluripotent stem cells (PSC) are to achieve their full potential. Here, we first used two protein factors (LIF and FGF2) and kinase inhibitor combinations in attempts to convert primed type lentiviral-reprogrammed porcine induced PSC (Lv-piPSC) into naïve-like state and developed a medium called FL6i. In addition to FGF2 and LIF, this medium contained inhibitors of MAPK14, MAPK8, TGFB1, MAP2K1, GSK3A and BMP. Crucially, the usual TGFB1 and BMP4 protein components of many stem cell media were replaced in FL6i with inhibitors of TGFB1 and BMP. With this medium, Lv-piPSC were readily transformed from their original primed state into cells that formed colonies with typical features of naïve-state stem cells. The FL6i medium also assisted generation of naïve-type piPSC lines from porcine embryonic fibroblasts with non-integrating episomal plasmids (Epi-piPSC). These lines, despite retaining variable amounts of vector DNA, expressed higher endogenous pPOU5F1 and pSOX2 than Lv-piPSC. They have been cultured without obvious morphological change for >45 passages and retained pluripotent phenotypes in terms of upregulation of genes associated with pluripotency, low expression of genes linked to emergence of somatic cell lineages, and ability to generate well differentiated teratomas in immune-compromised mice. FL6i conditions, therefore, appear to support elevated pluripotent phenotypes. However, FL6i was less able to support the generation of embryonic stem cells from porcine blastocysts. Although colonies with dome-shaped morphologies were evident and the cells had some gene expression features linked to pluripotency, the phenotypes were ultimately not stable. Pathway analysis derived from RNAseq data performed on the various cell lines generated in this study suggest the benefits of employing the FL6i medium on porcine cells reside in its ability to minimize TGFB1 and BMP signaling, which would otherwise de-stabilize the stem cell state.
Disentangling charge carrier from photothermal effects in plasmonic metal nanostructures
Authors: Zhan Chao , Liu Bo-Wen , Huang Yi-Fan , Hu Shu , Ren Bin , Moskovits Martin , Tian Zhong-Qun
Published: June 2019

Plasmon-mediated chemical reactions (PMCRs) constitute a vibrant research field, advancing such goals as using sunlight to convert abundant precursors such as CO2 and water to useful fuels and chemicals. A key question in this burgeoning field which has not, as yet, been fully resolved, relates to the precise mechanism through which the energy absorbed through plasmonic excitation, ultimately drives such reactions. Among the multiple processes proposed, two have risen to the forefront: plasmon-increased temperature and generation of energetic charge carriers. However, it is still a great challenge to confidently separate these two effects and quantify their relative contribution to chemical reactions. Here, we describe a strategy based on the construction of a plasmonic electrode coupled with photoelectrochemistry, to quantitatively disentangle increased temperature from energetic charge carriers effects. A clear separation of the two effects facilitates the rational design of plasmonic nanostructures for efficient photochemical applications and solar energy utilization.
Tunable spinful matter wave valve
Authors: Zhao Yan-Jun , Yu Dongyang , Zhuang Lin , Gao Xianlong , Liu Wu-Ming
Published: June 2019

We investigate the transport problem that a spinful matter wave is incident on a strong localized spin-orbit-coupled Bose-Einstein condensate in optical lattices, where the localization is admitted by atom interaction only existing at one particular site, and the spin-orbit coupling arouse spatial rotation of the spin texture. We find that tuning the spin orientation of the localized Bose-Einstein condensate can lead to spin-nonreciprocal/spin-reciprocal transport, meaning the transport properties are dependent on/independent of the spin orientation of incident waves. In the former case, we obtain the conditions to achieve transparency, beam-splitting, and blockade of the incident wave with a given spin orientation, and furthermore the ones to perfectly isolate incident waves of different spin orientation, while in the latter, we obtain the condition to maximize the conversion of different spin states. The result may be useful to develop a novel spinful matter wave valve that integrates spin switcher, beam-splitter, isolator, and converter. The method can also be applied to other real systems, e.g., realizing perfect isolation of spin states in magnetism, which is otherwise rather difficult.
Tipping phenomena in typical dynamical systems subjected to parameter drift
Authors: Kaszás Bálint , Feudel Ulrike , Tél Tamás
Published: June 2019

Tipping phenomena, i.e. dramatic changes in the possible long-term performance of deterministic systems subjected to parameter drift, are of current interest but have not yet been explored in cases with chaotic internal dynamics. Based on the example of a paradigmatic low-dimensional dissipative system subjected to different scenarios of parameter drifts of non-negligible rates, we show that a number of novel types of tippings can be observed due to the topological complexity underlying general systems. Tippings from and into several coexisting attractors are possible, and one can find fractality-induced tipping, the consequence of the fractality of the scenario-dependent basins of attractions, as well as tipping into a chaotic attractor. Tipping from or through an extended chaotic attractor might lead to random tipping into coexisting regular attractors, and rate-induced tippings appear not abruptly as phase transitions, rather they show up gradually when the rate of the parameter drift is increased. Since chaotic systems of arbitrary time-dependence call for ensemble methods, we argue for a probabilistic approach and propose the use of tipping probabilities as a measure of tipping. We numerically determine these quantities and their parameter dependence for all tipping forms discussed.
New insights of low-temperature plasma effects on germination of three genotypes of Arabidopsis thaliana seeds under osmotic and saline stresses
Authors: Bafoil Maxime , Le Ru Aurélie , Merbahi Nofel , Eichwald Olivier , Dunand Christophe , Yousfi Mohammed
Published: June 2019

In order to investigate the effects of low temperature plasmas on germination of Arabidopsis thaliana seeds, a dielectric barrier discharge device generating the plasma in ambient air was used. To highlight the different plasma effects on the seed surface, saline and osmotic stresses were considered in the case of reference Col-0 seeds and two further seed coat mutants gl2 and gpat5 to better analyse the seed surface changes and their consequences on germination. The GL2 gene encode a transcription factor controlling the balance between the biosynthesis of fatty acids in the embryo and the production of mucilage and flavonoid pigments in the seed coat. The GPAT5 gene encode for an acyltransferase necessary for the accumulation of suberin in the seed coat which is essential for the embryo protection. The testa and endosperm ruptures are identified to note the germination stage. An increasing of germination rate, possibly due to the modification of mantle layers structure, is observed in most of cases, even in presence of saline or osmotic stress, after plasma treatment. Furthermore, we demonstrated that the germination rate of the gl2 mutant seeds is increased by at most 47% after plasma treatment, contrariwise, the germination of gpat5 mutant being initially lower is inhibited by the same plasma treatment. The scanning electron microscopy pictures and confocal microscopy fluorescence both showed changes of the exterior aspects of the seeds after plasma treatment. Considering these results, we assumed that lipid compounds can be found on the surface. To validate this hypothesis, permeability tests were performed, and it was clearly shown that a permeability decrease is induced by the low temperature plasma treatment.
Photoacoustics can image spreading depolarization deep in gyrencephalic brain
Authors: Kirchner Thomas , Gröhl Janek , Herrera Mildred A. , Adler Tim , Hernández-Aguilera Adrián , Santos Edgar , Maier-Hein Lena
Published: June 2019

Spreading depolarization (SD) is a self-propagating wave of near-complete neuronal depolarization that is abundant in a wide range of neurological conditions, including stroke. SD was only recently documented in humans and is now considered a therapeutic target for brain injury, but the mechanisms related to SD in complex brains are not well understood. While there are numerous approaches to interventional imaging of SD on the exposed brain surface, measuring SD deep in brain is so far only possible with low spatiotemporal resolution and poor contrast. Here, we show that photoacoustic imaging enables the study of SD and its hemodynamics deep in the gyrencephalic brain with high spatiotemporal resolution. As rapid neuronal depolarization causes tissue hypoxia, we achieve this by continuously estimating blood oxygenation with an intraoperative hybrid photoacoustic and ultrasonic imaging system. Due to its high resolution, promising imaging depth and high contrast, this novel approach to SD imaging can yield new insights into SD and thereby lead to advances in stroke, and brain injury research.
Optimization and control of the light environment for greenhouse crop production
Authors: Xin Pingping , Li Bin , Zhang Haihui , Hu Jin
Published: June 2019

Optimization and control of the greenhouse light environment is key to increasing crop yield and quality. However, the light saturation point impacts the efficient use of light. Therefore, the dynamic acquisition of the light saturation point that is influenced by changes in temperature and CO2 concentration is an important challenge for the development of greenhouse light environment control system. In view of this challenge, this paper describes a light environment optimization and control model based on a crop growth model for predicting cucumber photosynthesis. The photosynthetic rate values for different photosynthetic photon flux densities (PPFD), CO2 concentration, and temperature conditions provided to cucumber seedlings were obtained by using an LI-6400XT portable photosynthesis system during multi-factorial experiments. Based on the measured data, photosynthetic rate predictions were determined. Next, a support vector machine(SVM) photosynthetic rate prediction model was used to obtain the light response curve under other temperatures and CO2 conditions. The light saturation point was used to establish the light environment optimization and control model and to perform model validation. The slope of the fitting straight line comparing the measured and predicted light saturation point was 0.99, the intercept was 23.46 and the coefficient of determination was 0.98. The light control model was able to perform dynamic acquisition of the light saturation point and provide a theoretical basis for the efficient and accurate control of the greenhouse light environment.
Hybrid QSPR models for the prediction of the free energy of solvation of organic solute/solvent pairs
Authors: Borhani Tohid N. , García-Muñoz Salvador , Vanesa Luciani Carla , Galindo Amparo , Adjiman Claire S.
Published: June 2019

QSPR models predict the Gibbs free energy of solvation of organic solute/solvent pairs by combining quantum mechanical and experimental descriptors.
Biocompatible functionalisation of nanoclays for improved environmental remediation
Authors: Biswas Bhabananda , Warr Laurence N. , Hilder Emily F. , Goswami Nirmal , Rahman Mohammad M. , Churchman Jock G. , Vasilev Krasimir , Pan Gang , Naidu Ravi
Published: June 2019

This review presents a summary of modified nanoclays and new perspective of producing biocompatibly functionalised nanoclays for environmental remediation.
Observation of visible light activated photocatalytic degradation of stearic acid on thin films of tantalum oxynitride synthesized by aerosol assisted chemical vapour deposition
Authors: Cosham Samuel D. , Celorrio Veronica , Kulak Alexander N. , Hyett Geoffrey
Published: June 2019

Demonstration of photocatalytic stearic acid mineralisation by thin films of tantalum oxynitride.
Effects of cobalt substitution on ZnO surface reactivity and electronic structure
Authors: D’Agostino Domenico , Di Giorgio Cinzia , Bobba Fabrizio , Di Trolio Antonio , Alippi Paola , Cucolo Anna Maria , Amore Bonapasta Aldo
Published: June 2019

Lowering of the Fermi level and hindering of negative oxygen species adsorption are induced in ZnO by cobalt substitution (5%).
Calibration strategies to correct for matrix effects in direct analysis of urine by ICP OES: internal standardization and multi-energy calibration
Authors: Barros Ariane I. , Pinheiro Fernanda C. , Nóbrega Joaquim A.
Published: June 2019

Internal standardization and MEC can be used successfully to correct for matrix effects in direct analysis of urine by ICP OES.
Dysprosium complexes bearing unsupported DyIII–GeII/SnIImetal–metal bonds as single-ion magnets
Authors: Chen Shi-Ming , Xiong Jin , Zhang Yi-Quan , Ma Fang , Sun Hao-Ling , Wang Bing-Wu , Gao Song
Published: June 2019

We report here two dysprosium complexes bearing unsupported Dy–Ge/Sn metal–metal bonds which contain relatively large covalency. Both complexes can exhibit slow relaxation of magnetization at zero field with energy barriers of 485 and 620 K, respectively, and the blocking temperature of 6 K.
Fabrication of 2D metal–organic framework nanosheet@fiber composites by spray technique
Authors: Zhang Liying , Chen Huan , Bai Xiaojue , Wang Sha , Li Linlin , Shao Lei , He Wenxiu , Li Yunong , Wang Tieqiang , Zhang Xuemin , Chen Junyi , Fu Yu
Published: June 2019

The feasible and rapid spray technique has been applied to fabricate 2D MOF nanosheet@fiber with homogeneous dispersion and high coverage.
Bifunctional electrocatalysis for CO2 reduction via surface capping-dependent metal–oxide interactions
Authors: Wu Yueshen , Yuan Xiaolei , Tao Zixu , Wang Hailiang
Published: June 2019

Cetyltrimethylammonium bromide capping on Au renders desirable chemical interactions with SnO2, enabling selective bifunctional CO2 electroreduction.