bluuebunny/crossref_metadata_2025 huggingface dataset:
Relationships between childhood trauma and perceived stress in the general population: a network perspective
Authors: Betz Linda T. , Penzel Nora , Rosen Marlene , Kambeitz Joseph
Published: May 2020

Background

Experiences of childhood trauma (CT) are associated with increased psychological vulnerability. Past research suggests that CT might alter stress processing with a subsequent negative impact on mental health. However, it is currently unclear how different domains of CT exert effects on specific subjective experiences of stress during adulthood.

Methods

In the present study, we used network analysis to explore the complex interplay between distinct domains of CT and perceived stress in a large, general-population sample of middle-aged adults (N= 1252). We used a data-driven community-detection algorithm to identify strongly connected subgroups of items within the network. To assess the replicability of the findings, we repeated the analyses in a second sample (N= 862). Combining data from both samples, we evaluated network differences between men (n= 955) and women (n= 1159).

Results

Results indicate specific associations between distinct domains of CT and perceived stress. CT domains reflecting a dimension of deprivation, i.e. experiences of neglect, were associated exclusively to a stress network community representing low perceived self-efficacy. By contrast, CT associated with threat, i.e. experiences of abuse, was specifically related to a stress community reflecting perceived helplessness. Our results replicated with high accordance in the second sample. We found no difference in network structure between men and women, but overall a stronger connected network in women.

Conclusions

Our findings emphasize the unique role of distinct domains of CT in psychological stress processes in adulthood, implying opportunities for targeted interventions following distinct domains of CT.
Finding independent transversals efficiently
Authors: Graf Alessandra , Haxell Penny
Published: May 2020

We give an efficient algorithm that, given a graph G and a partition V1,…,Vm of its vertex set, finds either an independent transversal (an independent set {v1,…,vm} in G such that ${v_i} \in {V_i}$ for each i), or a subset ${\cal B}$ of vertex classes such that the subgraph of G induced by $\bigcup\nolimits_{\cal B}$ has a small dominating set. A non-algorithmic proof of this result has been known for a number of years and has been used to solve many other problems. Thus we are able to give algorithmic versions of many of these applications, a few of which we describe explicitly here.
-CONVERGENCES OF WEIGHTED AVERAGED PROJECTIONS IN SPACES
Authors: CHOI BYOUNG JIN
Published: May 2020

We first introduce the weighted averaged projection sequence in $\text{CAT}(\unicode[STIX]{x1D705})$ spaces and then we establish some inequalities for the weighted averaged projection sequence. Using the inequalities, we prove the asymptotic regularity and the $\unicode[STIX]{x1D6E5}$-convergence of the weighted averaged projection sequence. Furthermore, we prove the strong convergence of the sequence under certain regularity or compactness conditions on $\text{CAT}(\unicode[STIX]{x1D705})$ spaces.
Stellar populations in the BAaDE survey
Authors: Lewis Megan O. , Pihlström Ylva M. , Sjouwerman Loránt O. , Stroh Michael C. ,   the BAaDE team
Published: May 2020

The BAaDE (Bulge Asymmetries and Dynamical Evolution) project is an SiO maser survey of the Galactic Plane. About 19,000 sources have been observed at 43 GHz with the VLA, and the production of spectra for each of these sources is well underway. The primary goal of the project is to collect line-of-sight velocities for all the detected masers in the sample to probe Galactic dynamics. With an expected detection rate of over 60% we should collect over 11,000 velocities to probe the Galactic potential. The survey is also a large sample of infrared sources to explore the different evolved stellar populations within the Milky Way. So far we discern three distinct groups in the BAaDE sample: the main group containing oxygen-rich, evolved stars with a high SiO maser detection rate, a much smaller population of carbon-rich evolved stars, and finally a group of likely young stellar objects with no maser emission. These populations are separated using 2MASS and MSX color-color diagrams, and we find a particularly useful cut between the young and evolved objects using the MSX [D] –[E] color. Identification of these populations will isolate BAaDE’s evolved star sample, and will more tightly define the region in IR color-color diagrams where SiO masers occur yielding a better understanding of these kinematical probes. Using our color-divisions we can also study the distribution of each of the populations within the Galactic Plane.
Stellar and dynamical masses of brightest cluster galaxies
Authors: Loubser S. I.
Published: May 2020

We investigate the stellar and dynamical mass profiles of 32 brightest cluster galaxies (BCGs, MK = −25.7 to −27.8 mag) in massive clusters (0.05 < z < 0.30), and in particular the rising velocity dispersion profiles of 23 of these BCGs found in Loubser et al. (2018). We make comprehensive measurements of the Gauss-Hermite higher order velocity moments h3 and h4, and find positive central values for h4 for all the BCGs. We model the stellar and dynamical mass profiles of 25 of the BCGs using the Multi-Gaussian Expansion (MGE) and Jeans Anisotropic Method (JAM) for an axisymmetric case, deriving the stellar mass-to-light ratio (ϒ*DYN), and anisotropy (βz). We further explicitly add a dark matter halo mass component (MDM within r200) which we constrain from weak lensing results. In this proceedings, we summarise the study and show an example of the results.
Accreted Globular Clusters in external galaxies: Why adaptive dynamics is not the solution
Authors: Lilleengen Sophia , Trick Wilma , van de Ven Glenn
Published: May 2020

Many astrophysical and galaxy-scale cosmological problems require a well determined gravitational potential which is often modeled by observers under strong assumptions. Globular clusters (GCs) surrounding galaxies can be used as dynamical tracers of the luminous and dark matter distribution at large (kpc) scales. A natural assumption for modeling the gravitational potential is that GCs accreted in the same dwarf galaxy merger event move at the present time on similar orbits in the host galaxy and should therefore have similar actions. We investigate this idea in one realistic Milky Way like galaxy of the cosmological N-body simulation suite Auriga. We show how the actions of accreted stellar particles in the simulation evolve and that minimizing the standard deviation of GCs in action space, however, cannot constrain the true potential. This approach known as ‘adaptive dynamics’ does therefore not work for accreted GCs.
Milky Way’s structure based on thousands of Cepheids and RR Lyrae stars from OGLE
Authors: Pietrukowicz Pawel
Published: May 2020

Classical Cepheids and RR Lyrae-type variable stars are widely-used tracers of young (< 300 Myr) and old (> 10 Gyr) stellar populations, respectively. These stars also serve as distance indicators allowing for Galactic structure studies. Robust detection of pulsating variables requires precise and relatively frequent observations over several years. Recently, the OGLE survey has discovered nearly 1,300 new genuine classical Cepheids and 15,000 RR Lyrae stars along the southern Galactic plane. Here, we present the picture of the Milky Way’s thin disk drawn with the Cepheids and the view of the Galactic old population that emerges from the set of known RR Lyrae stars.
Kinematical signatures of disc instabilities and secular evolution in the MUSE TIMER Survey
Authors: Gadotti Dimitri A. , Bittner Adrian , Falcón-Barroso Jesus , Méndez-Abreu Jairo ,   the TIMER Team
Published: May 2020

The MUSE TIMER Survey has obtained high signal and high spatial resolution integral-field spectroscopy data of the inner ~ 6×6 kpc of 21 nearby massive disc galaxies. This allows studies of the stellar kinematics of the central regions of massive disc galaxies that are unprecedented in spatial resolution. We confirm previous predictions from numerical and hydrodynamical simulations of the effects of bars and inner bars on stellar and gaseous kinematics, and also identify box/peanuts via kinematical signatures in mildly and moderately inclined galaxies, including a box/peanut in a face-on inner bar. In 20/21 galaxies we find inner discs and show that their properties are fully consistent with the bar-driven secular evolution picture for their formation. In addition, we show that these inner discs have, in the region where they dominate, larger rotational support than the main galaxy disc, and discuss how their stellar population properties can be used to estimate when in cosmic history the main bar formed. Our results are compared with photometric studies in the context of the nature of galaxy bulges and we show that inner discs are identified in image decompositions as photometric bulges with exponential profiles (i.e., Sérsic indices near unity).
Detecting tidal tail of the globular cluster Whiting 1
Authors: Nie Jundan , Tian Hao
Published: May 2020

Whiting 1 is a faint and young globular cluster embedded in the Sag dSph. It has similar distance, metalicity and radial velocity with the trailing stream of the Sag. Due to these special properties, Whiting 1 was suggested to be associated with the trailing stream of Sag. However, its origin is still unclear and further investigation of its relation with Sgr dSph is needed. In this work, we use DECaLS data to search the tidal tail of Whiting 1, with the aim of looking for spatial connection between Whiting 1 and Sgr dSph. With Matched Filter method, we detected a tidal tail around the main body of Whiting 1. This tail extends to at least 0.5 degree and aligns with the mean orbit direction of Sgr dSph. This tail is newly detected and it provides additional evidence of the association between Whiting 1 and Sgr trailing stream.
Schwarzschild modeling of barred galaxies
Authors: Vasiliev Eugene , Valluri Monica
Published: May 2020

We review the Schwarzschild orbit-superposition approach and present a new implementation of this method, which can deal with a large class of systems, including rotating barred disk galaxies. We discuss two conceptual problems in this field: the intrinsic degeneracy of determining the potential from line-of-sight kinematics, and the non-uniqueness of deprojection and related biases in potential inference, especially acute for triaxial bars. When applied to mock datasets with known 3d shape, our method correctly recovers the pattern speed and other potential parameters. However, more work is needed to systematically address these two problems for real observational datasets.
The demographics of central massive black holes in low-mass early-type galaxies
Authors: Nguyen Dieu D.
Published: May 2020

The existence intermediate mass black holes (IMBH, MBH ≲ 106M⊙) at the centers low-mass galaxies with stellar masses between (1–10)×10M⊙ are key to constraining the origin of black hole (BH) seeds and understanding the physics deriving the co-evolution of central BHs and their host galaxies. However, finding and weighing IMBH is challenging. Here, we present the first observational evidence for such IMBHs at the centers of the five nearest early-type galaxies (D < 3.5 Mpc, ETGs) revealed by adaptive optics kinematics from Gemini and VLT and high-resolution HST spectroscopy. We find that all five galaxies appear to host IMBHs with four of the five having masses below 1 million M⊙ and the lowest mass BH being only ∼7,000 M⊙. This work provides a first glimpse of the demographics of IMBHs in this galaxy mass range and at velocity dispersions < 70 km/s, and thus provides an important extension to the bulge mass and galaxy dispersion scaling relations. The ubiquity of central BHs in these galaxies provides a unique constraint on BH seed formation scenarios, favoring a formation mechanism that produces an abundance of low-mass seed BHs.
Key dynamical results from the SAMI Galaxy Survey
Authors: van de Sande Jesse , Bland-Hawthorn Joss , Barat Dilyar , Brough Sarah , Bryant Julia J. , Croom Scott M. , Cortese Luca ,   the SAMI Galaxy Survey collaboration
Published: May 2020

We present an overview of recent key results from the SAMI Galaxy Survey on the build-up of mass and angular momentum in galaxies across morphology and environment. The SAMI Galaxy survey is a multi-object integral field spectroscopic survey and provides a wealth of spatially-resolved, two-dimensional stellar and gas measurements for galaxies of all morphological types, with high-precision due the stable spectral resolution of the AAOmega spectrograph. The sample size of ~3000 galaxies allows for dividing the sample in bins of stellar mass, environment, and star-formation or morphology, whilst maintaining a statistical significant number of galaxies in each bin. By combining imaging, spatially resolved dynamics, and stellar population measurements, our result demonstrate the power of utilising integral field spectroscopy on a large sample of galaxies to further our understanding of physical processes involved in the build-up of stellar mass and angular momentum in galaxies.
Sex-dependent metabolic effects of pregestational exercise on prenatally stressed mice
Authors: Luft Carolina , Levices Isadora Perez , Pedrazza Leonardo , de Oliveira Jarbas Rodrigues , Donadio Márcio Vinícius Fagundes
Published: May 2020

Stressful events during the prenatal period have been related to hyperactive hypothalamic–pituitary–adrenal (HPA) axis responses as well as metabolic changes in adult life. Moreover, regular exercise may contribute to the improvement of the symptoms associated with stress and stress-related chronic diseases. Therefore, this study aims to investigate the effects of exercise, before the gestation period, on the metabolic changes induced by prenatal stress in adult mice. Female Balb/c mice were divided into three groups: control (CON), prenatal restraint stress (PNS) and exercise before the gestational period plus PNS (EX + PNS). When adults, the plasmatic biochemical analysis, oxidative stress, gene expression of metabolic-related receptors and sex differences were assessed in the offspring. Prenatal stress decreased neonatal and adult body weight when compared to the pregestational exercise group. Moreover, prenatal stress was associated with reduced body weight in adult males. PNS and EX + PNS females showed decreased hepatic catalase. Pregestational exercise prevented the stress-induced cholesterol increase in females but did not prevent the liver mRNA expression reduction on the peroxisome proliferator-activated receptors (PPARs) α and γ in PNS females. Conversely, PNS and EX + PNS males showed an increased PPARα mRNA expression. In conclusion, pregestational exercise prevented some effects of prenatal stress on metabolic markers in a sex-specific manner.
Observing Rivers With Varying Spatial Scales
Authors: Rodríguez Ernesto , Durand Michael , Frasson Renato Prata de Moraes
Published: May 2020

The National Aeronautics and Space Administration/Centre national d’études spatiales Surface Water and Ocean Topography (SWOT) mission will estimate global river discharge using remote sensing. Synoptic remote sensing data extend in situ point measurements but, at any given point, are generally less accurate. We address two questions:(1)What are the scales at which river dynamics can be observed, given spatial sampling and measurement noise characteristics? (2) Is there an equation whose variables are the averaged hydraulic quantities obtained by remote sensing and which describes the dynamics of spatially averaged rivers?We use calibrated hydraulic models to examine the power spectra of the different terms in the momentum equation and conclude that the measurement of river slope sets the scale at which rivers can be observed. We introduce thereach‐averaged Saint Venant equationsthat involve only observable hydraulic variations and which parametrize within‐reach variability with a variability index that multiplies the friction coefficient and leads to an increased “effective” friction coefficient. An exact expression is derived for the increase in the effective friction coefficient, and we propose an approximation that requires only estimates of the hydraulic parameter variances. We validate the results using a large set of hydraulic models and find that the approximated variability index is most faithful when the river parameters obey lognormal statistics. The effective friction coefficient, which can vary from a few percent to more than 50% of the point friction coefficient, is proportional to the riverbed elevation variance and inversely proportional to the depth. This has significant implications for estimating discharge from SWOT  data.
Multilevel Monte Carlo Predictions of First Passage Times in Three‐Dimensional Discrete Fracture Networks: A Graph‐Based Approach
Authors: Berrone S. , Hyman J. D. , Pieraccini S.
Published: May 2020

We present a method combining multilevel Monte Carlo (MLMC) and a graph‐based primary subnetwork identification algorithm to provide estimates of the mean and variance of the distribution of first passage times in fracture media at significantly lower computational cost than standard Monte Carlo (MC) methods. Simulations of solute transport are performed using a discrete fracture network (DFN), and instead of using various grid resolutions for levels in the MLMC, which is standard practice in MLMC, we identify a hierarchy of subnetworks in the DFN based on the shortest topological paths through the network using a graph‐based method. While the mean of these ensembles is of critical importance, the variance is also essential in fractured media where uncertainty is an overarching theme, and understanding variability across an ensemble is a requirement for safety assessments. The method provides good estimates of the mean and variance at two orders of magnitude lower computational cost than MC.
Severe Magnetic Fluctuations in the Near‐Earth Magnetotail: Spectral Analysis and Dependence on Solar Activity
Authors: Xu Heqiucen , Shiokawa Kazuo
Published: May 2020

Magnetic fluctuations in the near‐Earth magnetotail are an important signature of substorm onset. In a previous statistical study, we reported their occurrence rates, spatial distributions, and relationship with plasma flows. In the present study, we investigated their spectral properties using 11 years of measurements from the Time History of Events and Macroscale Interactions during Substorms mission for 2008–2018. We found 10,848 severe magnetic fluctuation events with
, where σB and
are the standard deviation and average, respectively, of the magnetic field intensity for the local proton gyroperiod. The occurrence rates of severe magnetic fluctuations show no clear dependence on the F10.7 index in one solar cycle. We extracted 36 dipolarization events with severe magnetic fluctuations. In the power spectral density (PSD) of the magnetic fluctuations during dipolarizations, the steepness of the spectral slope increased with increasing frequency in almost all the events. The average PSDs are shown sorted by (a) distance to the neutral sheet and (b) ambient magnetic field intensity. In all groups, the slopes of the average PSDs increased abruptly from below ∼10−1.3 Hz (0.05 Hz) to above ∼10−1.3 Hz, which is close to the gyrofrequency of O+ ions. It is the first time that a change of slope near the proton gyrofrequency (frequency range: 0.05–1 Hz) was found in cases of larger ambient magnetic field intensity, implying that the magnetic fluctuations were relatively strong near the proton gyrofrequency. These results suggest that the magnetic fluctuations contribute to the nonmagnetohydrodynamic effect in the ion motion.
A dose-finding Phase 2 study of single agent isatuximab (anti-CD38 mAb) in relapsed/refractory multiple myeloma
Authors: Mikhael Joseph , Richter Joshua , Vij Ravi , Cole Craig , Zonder Jeffrey , Kaufman Jonathan L. , Bensinger William , Dimopoulos Meletios , Lendvai Nikoletta , Hari Parameswaran , Ocio Enrique M. , Gasparetto Cristina , Kumar Shaji , Oprea Corina , Chiron Marielle , Brillac Claire , Charpentier Eric , San-Miguel Jesús , Martin Thomas
Published: May 2020

A Phase 2 dose-finding study evaluated isatuximab, an anti-CD38 monoclonal antibody, in relapsed/refractory multiple myeloma (RRMM; NCT01084252). Patients with ≥3 prior lines or refractory to both immunomodulatory drugs and proteasome inhibitors (dual refractory) were randomized to isatuximab 3 mg/kg every 2 weeks (Q2W), 10 mg/kg Q2W(2 cycles)/Q4W, or 10 mg/kg Q2W. A fourth arm evaluated 20 mg/kg QW(1 cycle)/Q2W. Patients (N = 97) had a median (range) age of 62 years (38–85), 5 (2–14) prior therapy lines, and 85% were double refractory. The overall response rate (ORR) was 4.3, 20.0, 29.2, and 24.0% with isatuximab 3 mg/kg Q2W, 10 mg/kg Q2W/Q4W, 10 mg/kg Q2W, and 20 mg/kg QW/Q2W, respectively. At doses ≥10 mg/kg, median progression-free survival and overall survival were 4.6 and 18.7 months, respectively, and the ORR was 40.9% (9/22) in patients with high-risk cytogenetics. CD38 receptor density was similar in responders and non-responders. The most common non-hematologic adverse events (typically grade ≤2) were nausea (34.0%), fatigue (32.0%), and upper respiratory tract infections (28.9%). Infusion reactions (typically with first infusion and grade ≤2) occurred in 51.5% of patients. In conclusion, isatuximab is active and generally well tolerated in heavily pretreated RRMM, with greatest efficacy at doses ≥10 mg/kg.
Cuprous oxide nanoparticles trigger reactive oxygen species-induced apoptosis through activation of erk-dependent autophagy in bladder cancer
Authors: Xiong Qiao , Liu Anwei , Ren Qian , Xue Yongping , Yu Xiaowen , Ying Yidie , Gao Hongliang , Tan Haoyuan , Zhang Zhensheng , Li Wei , Zeng Shuxiong , Xu Chuanliang
Published: May 2020

Cisplatin-based chemotherapy is the first-line treatment for patients with advanced bladder cancer. However, as more than 50% of patients are ineligible for cisplatin-based chemotherapy, there is an urgent need to develop new drugs. Cuprous oxide nanoparticles (CONPs), as a new nano-therapeutic agent, have been proved to be effective in many kinds of tumors. In the present study, CONPs showed dose-dependent and time-dependent inhibitory effects on various bladder cancer cell lines (T24, J82, 5637, and UMUC3) and weak inhibitory effects on non-cancerous epithelial cells (SVHUCs). We found that CONPs induced cell cycle arrest and apoptosis in bladder cancer cells. We further demonstrated that the potential mechanisms of CONP-induced cytotoxicity were apoptosis, which was triggered by reactive oxygen species through activation of ERK signaling pathway, and autophagy. Moreover, the cytotoxic effect of CONPs on bladder cancer was confirmed both in orthotopic xenografts and subcutaneous nude mouse models, indicating that CONPs could significantly suppress the growth of bladder cancer in vivo. In further drug combination experiments, we showed that CONPs had a synergistic drug–drug interaction with cisplatin and gemcitabine in vitro, both of which are commonly used chemotherapy agents for bladder cancer. We further proved that CONPs potentiated the antitumor activity of gemcitabine in vivo without exacerbating the adverse effects, suggesting that CONPs and gemcitabine can be used for combination intravesical chemotherapy. In conclusion, our preclinical data demonstrate that CONPs are a promising nanomedicine against bladder cancer and provide good insights into the application of CONPs and gemcitabine in combination for intravesical bladder cancer treatment.
Stimuli-responsive hydrogels as a model of the dynamic cellular microenvironment
Authors: Tanaka Motomu , Nakahata Masaki , Linke Philipp , Kaufmann Stefan
Published: May 2020

Ample evidence has demonstrated that biological cells not only react to biochemical cues from the surrounding microenvironments but also sensitively detect the mechanical properties of the extracellular matrix and neighboring cells to adapt their shape, function, and fate. Mechanical aspects in biology, called mechanobiology, have been attracting biologists, chemists, physicists, and mechanical engineers. However, most in vitro studies to date have heavily relied on covalently cross-linked hydrogels with prefixed and hence unchangeable mechanical properties, although the mechanical properties of the cellular microenvironment are never uniform or static. From this context, stimuli-responsive hydrogels are highly attractive as surrogate materials that can simulate dynamic physical microenvironments in vivo. This review tries to provide a comprehensive overview of previous achievements, present pitfalls and challenges, and future perspectives on the recent development of stimuli-responsive hydrogel materials for the dynamic control of cell behavior.
Heteronuclear soliton molecules in optical microresonators
Authors: Weng Wenle , Bouchand Romain , Lucas Erwan , Obrzud Ewelina , Herr Tobias , Kippenberg Tobias J.
Published: May 2020

Optical soliton molecules are bound states of solitons that arise from the balance between attractive and repulsive effects. Having been observed in systems ranging from optical fibres to mode-locked lasers, they provide insights into the fundamental interactions between solitons and the underlying dynamics of the nonlinear systems. Here, we enter the multistability regime of a Kerr microresonator to generate superpositions of distinct soliton states that are pumped at the same optical resonance, and report the discovery of heteronuclear dissipative Kerr soliton molecules. Ultrafast electrooptical sampling reveals the tightly short-range bound nature of such soliton molecules, despite comprising cavity solitons of dissimilar amplitudes, durations and carrier frequencies. Besides the significance they hold in resolving soliton dynamics in complex nonlinear systems, such heteronuclear soliton molecules yield coherent frequency combs whose unusual mode structure may find applications in metrology and spectroscopy.
Room-temperature coherent control of implanted defect spins in silicon carbide
Authors: Yan Fei-Fei , Yi Ai-Lun , Wang Jun-Feng , Li Qiang , Yu Pei , Zhang Jia-Xiang , Gali Adam , Wang Ya , Xu Jin-Shi , Ou Xin , Li Chuan-Feng , Guo Guang-Can
Published: May 2020

Recently, vacancy-related spin defects in silicon carbide (SiC) have been demonstrated to be potentially suitable for versatile quantum interface building and scalable quantum network construction. Significant efforts have been undertaken to identify spin systems in SiC and to extend their quantum capabilities using large-scale growth and advanced nanofabrication methods. Here we demonstrated a type of spin defect in the 4H polytype of SiC generated via hydrogen ion implantation with high-temperature post-annealing, which is different from any known defects. These spin defects can be optically addressed and coherently controlled even at room temperature, and their fluorescence spectrum and optically detected magnetic resonance spectra are different from those of any previously discovered defects. Moreover, the generation of these defects can be well controlled by optimizing the annealing temperature after implantation. These defects demonstrate high thermal stability with coherently controlled electron spins, facilitating their application in quantum sensing and masers under harsh conditions.
Evaluation of heterologous prime-boost vaccination strategies using chimpanzee adenovirus and modified vaccinia virus for TB subunit vaccination in rhesus macaques
Authors: Vierboom Michel P. M. , Chenine Agnes L. , Darrah Patricia A. , Vervenne Richard A. W. , Boot Charelle , Hofman Sam O. , Sombroek Claudia C. , Dijkman Karin , Khayum Mohamed A. , Stammes Marieke A. , Haanstra Krista G. , Hoffmann Chantal , Schmitt Doris , Silvestre Nathalie , White Alexander G. , Borish H. Jacob , Seder Robert A. , Ouaked Nadia , Leung-Theung-Long Stephane , Inchauspé Geneviève , Anantha Ravi , Limbach Mary , Evans Thomas G. , Casimiro Danilo , Lempicki Maria , Laddy Dominick J. , Bonavia Aurelio , Verreck Frank A. W.
Published: May 2020

Tuberculosis (TB) still is the principal cause of death from infectious disease and improved vaccination strategies are required to reduce the disease burden and break TB transmission. Here, we investigated different routes of administration of vectored subunit vaccines based on chimpanzee-derived adenovirus serotype-3 (ChAd3) for homologous prime-boosting and modified vaccinia virus Ankara (MVA) for heterologous boosting with both vaccine vectors expressing the same antigens from Mycobacterium tuberculosis (Ag85B, ESAT6, Rv2626, Rv1733, RpfD). Prime-boost strategies were evaluated for immunogenicity and protective efficacy in highly susceptible rhesus macaques. A fully parenteral administration regimen was compared to exclusive respiratory mucosal administration, while parenteral ChAd3-5Ag prime-boosting and mucosal MVA-5Ag boosting were applied as a push-and-pull strategy from the periphery to the lung. Immune analyses corroborated compartmentalized responses induced by parenteral versus mucosal vaccination. Despite eliciting TB-specific immune responses, none of the investigational regimes conferred a protective effect by standard readouts of TB compared to non-vaccinated controls, while lack of protection by BCG underpinned the stringency of this non-human primate test modality. Yet, TB manifestation after full parenteral vaccination was significantly less compared to exclusive mucosal vaccination.
Bioprocess development for L-asparaginase production by Streptomyces rochei, purification and in-vitro efficacy against various human carcinoma cell lines
Authors: El-Naggar Noura El-Ahmady , El-Shweihy Nancy M.
Published: May 2020

In the near future, the demand for L-asparaginase is expected to rise several times due to an increase in its clinical and industrial applications in various industrial sectors, such as food processing. Streptomyces sp. strain NEAE-K is potent L-asparaginase producer, isolated and identified as new subsp. Streptomyces rochei subsp. chromatogenes NEAE-K and the sequence data has been deposited under accession number KJ200343 at the GenBank database. Sixteen different independent factors were examined for their effects on L-asparaginase production by Streptomyces rochei subsp. chromatogenes NEAE-K under solid state fermentation conditions using Plackett–Burman design. pH, dextrose and yeast extract were the most significant factors affecting L-asparaginase production. Thus, using central composite design, the optimum levels of these variables were determined. L-asparaginase purification was carried out by ammonium sulfate followed by DEAE-Sepharose CL-6B ion exchange column with a final purification fold of 16.18. The monomeric molecular weight of the purified L-asparaginase was 64 kD as determined by SDS-PAGE method. The in vitro effects of L-asparaginase were evaluated on five human tumor cell lines and found to have a strong anti-proliferative effects. The results showed that the strongest cytotoxic effect of L-asparaginase was exerted on the HeLa and HepG-2 cell lines (IC50 = 2.16 ± 0.2 and 2.54 ± 0.3 U/mL; respectively). In addition, the selectivity index of L-asparaginase against HeLa and HepG-2 cell lines was 3.94 and 3.35; respectively.
Reinforcement Quantum Annealing: A Hybrid Quantum Learning Automata
Authors: Ayanzadeh Ramin , Halem Milton , Finin Tim
Published: May 2020

We introduce the notion of reinforcement quantum annealing (RQA) scheme in which an intelligent agent searches in the space of Hamiltonians and interacts with a quantum annealer that plays the stochastic environment role of learning automata. At each iteration of RQA, after analyzing results (samples) from the previous iteration, the agent adjusts the penalty of unsatisfied constraints and re-casts the given problem to a new Ising Hamiltonian. As a proof-of-concept, we propose a novel approach for casting the problem of Boolean satisfiability (SAT) to Ising Hamiltonians and show how to apply the RQA for increasing the probability of finding the global optimum. Our experimental results on two different benchmark SAT problems (namely factoring pseudo-prime numbers and random SAT with phase transitions), using a D-Wave 2000Q quantum processor, demonstrated that RQA finds notably better solutions with fewer samples, compared to the best-known techniques in the realm of quantum annealing.
Probabilistic risk assessment of dietary exposure to aflatoxin B1 in Guangzhou, China
Authors: Zhang Weiwei , Liu Yufei , Liang Boheng , Zhang Yuhua , Zhong Xianwu , Luo Xiaoyan , Huang Jie , Wang Yanyan , Cheng Weibin , Chen Kuncai
Published: May 2020

Aflatoxin B1 (AFB1) contamination in foods is an important health challenge for low-and middle-income countries in subtropical regions. AFB1 has been detected in a variety of foodsin Guangzhou, while the risk of dietary exposure is unknown. This study aimed to assess the probabilistic risk of dietary exposure to AFB1 contamination in food stuffs in Guangzhou by using margin of exposure (MOE) and quantitative liver cancer risk approaches. A total of1854 AFB1-contaminated foodstuffs were sampled in supermarkets, agricultural markets, retail shops, and family workshops from 11 districts of Guangzhou, and AFB1 content was determined by HPLC-fluorescence detector. In total, 9.9% (184/1854) of the test samples had AFB1 concentrations above the limit of detection. Home-made peanut oil had the highest AFB1 concentration, with a mean value of 38.74 ± 47.45 μg kg−1. The average MOE levels of Guangzhou residents ranged from 100 to 1000. The risk of liver cancer was 0.0264 cancers (100,000 population year)−1. The health risks of suburban people were higher than those of urban people, and home-made peanut oil was the main contributorto dietary exposure to AFB1 among suburban residents in Guangzhou. The production of home-made peanut oil should be supervised to reduce the risk of AFB1 exposure.
Ultra Wideband Radar Cross Section Reduction by using non-Resonant Unit Cells
Authors: Nadi Morteza , Sedighy Seyed Hassan , Khalaj-Amirhosseini Mohamad
Published: May 2020

A general approach is proposed to design ultra-wideband radar cross section reduction (RCSR) metasurface by using non-resonant unit cells in chessboard arrangement. The proposed miniaturized artificial magnetic conductor unit cell is composed of two stacked non-resonant patches separated from one another by thin dielectric substrates. The genetic optimization algorithm is used to optimize the unit cell design parameters and obtain wide 10-dB RCSR bandwidth. The proposed approach is performed to design three different RCSR metasurfaces, ideal, ROGERS and low cost. The low cost RCSR metasurface composed of low cost commercially available FR-4 substrate is fabricated and tested which reduces RCS more than 10-dB from 5.22 GHz to 30.85 GHz, 142% fractional bandwidth. This metasurface has significantly wider RCSR bandwidth rather than the state of the art references as well as low cost, simple and light weight structure which facilities its practical applications.
Serum neurofilament light chain levels as a biomarker of neuroaxonal injury and severity of oxaliplatin-induced peripheral neuropathy
Authors: Kim Su-Hyun , Choi Moon Ki , Park Na Young , Hyun Jae-Won , Lee Min Young , Kim Ho Jin , Jung Su Kyung , Cha Yongjun
Published: May 2020

We set out to determine the usability of serum neurofilament light chain (sNfL), serum glial fibrillary acidic protein (sGFAP), and retinal parameters by using optical coherence tomography (OCT) as reliable biomarkers of the progression of oxaliplatin-induced peripheral neuropathy (OIPN). Forty-three patients scheduled to undergo oxaliplatin-based chemotherapy at the National Cancer Center of Korea between June 2018 and October 2019 were prospectively assessed at baseline, 3 months, and 6 months of chemotherapy. Patients were assessed on clinical scales and underwent OCT, sNfL, and sGFAP level measurement at each follow-up visit. By applying the National Cancer Institute-Common Toxicity Criteria (NCI-CTC), OIPN was classified as grade 1 in 12 (28%) patients, grade 2 in 25 (58%), and grade 3 in 5 (12%) at 6 months of chemotherapy. sNfL levels increased during oxaliplatin administration, while serial sGFAP levels or retinal parameters did not change. Patients with grade-3 OIPN showed significantly higher mean sNfL levels than patients with grade 0–2 OIPN at 6 months of treatment. At 4–6 months after completion of chemotherapy, sNfL levels were significantly reduced compared to the levels at 6 months of chemotherapy. Monitoring of sNfL during chemotherapy can indicate ongoing neuroaxonal injury and the severity of OIPN.
Machine Learning (ML) based-method applied in recurrent pregnancy loss (RPL) patients diagnostic work-up: a potential innovation in common clinical practice
Authors: Bruno V. , D’Orazio M. , Ticconi C. , Abundo P. , Riccio S. , Martinelli E. , Rosato N. , Piccione E. , Zupi E. , Pietropolli A.
Published: May 2020

RPL is a very debated condition, in which many issues concerning definition, etiological factors to investigate or therapies to apply are still controversial. ML could help clinicians to reach an objectiveness in RPL classification and access to care. Our aim was to stratify RPL patients in different risk classes by applying an ML algorithm, through a diagnostic work-up to validate it for the appropriate prognosis and potential therapeutic approach. 734 patients were enrolled and divided into 4 risk classes, according to the numbers of miscarriages. ML method, called Support Vector Machine (SVM), was used to analyze data. Using the whole set of 43 features and the set of the most informative 18 features we obtained comparable results: respectively 81.86 ± 0.35% and 81.71 ± 0.37% Unbalanced Accuracy. Applying the same method, introducing the only features recommended by ESHRE, a correct classification was obtained only in 58.52 ± 0.58%. ML approach could provide a Support Decision System tool to stratify RPL patients and address them objectively to the proper clinical management.
Differential responses to kinase inhibition in FGFR2-addicted triple negative breast cancer cells: a quantitative phosphoproteomics study
Authors: Cunningham Debbie L. , Sarhan Adil R. , Creese Andrew J. , Larkins Katherine P. B. , Zhao Hongyan , Ferguson Harriet R. , Brookes Katie , Marusiak Anna A. , Cooper Helen J. , Heath John K.
Published: May 2020

Fibroblast Growth Factor (FGF) dependent signalling is frequently activated in cancer by a variety of different mechanisms. However, the downstream signal transduction pathways involved are poorly characterised. Here a quantitative differential phosphoproteomics approach, SILAC, is applied to identify FGF-regulated phosphorylation events in two triple- negative breast tumour cell lines, MFM223 and SUM52, that exhibit amplified expression of FGF receptor 2 (FGFR2) and are dependent on continued FGFR2 signalling for cell viability. Comparative Gene Ontology proteome analysis revealed that SUM52 cells were enriched in proteins associated with cell metabolism and MFM223 cells enriched in proteins associated with cell adhesion and migration. FGFR2 inhibition by SU5402 impacts a significant fraction of the observed phosphoproteome of these cells. This study expands the known landscape of FGF signalling and identifies many new targets for functional investigation. FGF signalling pathways are found to be flexible in architecture as both shared, and divergent, responses to inhibition of FGFR2 kinase activity in the canonical RAF/MAPK/ERK/RSK and PI3K/AKT/PDK/mTOR/S6K pathways are identified. Inhibition of phosphorylation-dependent negative-feedback pathways is observed, defining mechanisms of intrinsic resistance to FGFR2 inhibition. These findings have implications for the therapeutic application of FGFR inhibitors as they identify both common and divergent responses in cells harbouring the same genetic lesion and pathways of drug resistance.
Establishment of patient-derived xenografts from patients with gastrointestinal stromal tumors: analysis of clinicopathological characteristics related to engraftment success
Authors: Na Young-Soon , Ryu Min-Hee , Park Young Soo , Lee Chae-Won , Lee Ju-Kyung , Park Yangsoon , Park Jung Min , Ma Jungeun , Kang Yoon-Koo
Published: May 2020

Patient-derived xenografts (PDXs) can represent the heterogeneity and histological characteristics of tumors and are thus useful for testing the efficacy of anti-cancer drugs; however, PDXs are difficult to generate, especially for gastrointestinal stromal tumor (GIST). We analyzed the clinicopathologic factors associated with the successful establishment of GIST PDX in NOD.Cg-PrkdcscidIL2rgtm1Wjl/SzJ mice. We used 185 GIST tumor fragments from patients who underwent surgical resection prior to (n = 66; 35.7%) and after treatment (n = 119; 64.3%) with tyrosine kinase inhibitors. The overall success rate of PDX establishment was 17%; in univariate analysis, engraftment success was associated with after TKI treatment, larger tumor size, higher mitotic count, higher Ki-67 index, higher cellularity, presence of tumor necrosis, primary mutations in KIT exon 11, and originating from metastatic lesions. In multivariate analysis, higher Ki-67 index, after TKI treatment, and larger tumor size were independent factors for engraftment success. Immunohistochemistry in representative samples further corroborated the above results. These results will be useful in the establishment of PDX models from GISTs.
Niche shifts and environmental non-equilibrium undermine the usefulness of ecological niche models for invasion risk assessments
Authors: Pili Arman N. , Tingley Reid , Sy Emerson Y. , Diesmos Mae Lowe L. , Diesmos Arvin C.
Published: May 2020

Niche shifts and environmental non-equilibrium in invading alien species undermine niche-based predictions of alien species’ potential distributions and, consequently, their usefulness for invasion risk assessments. Here, we compared the realized climatic niches of four alien amphibian species (Hylarana erythraea, Rhinella marina, Hoplobatrachus rugulosus, andKaloula pulchra) in their native and Philippine-invaded ranges to investigate niche changes that have unfolded during their invasion and, with this, assessed the extent of niche conservatism and environmental equilibrium. We investigated how niche changes affected reciprocal transferability of ecological niche models (ENMs) calibrated using data from the species’ native and Philippine-invaded ranges, and both ranges combined. We found varying levels of niche change across the species’ realized climatic niches in the Philippines: climatic niche shift forH. rugulosus; niche conservatism forR. marinaandK. pulchra; environmental non-equilibrium in the Philippine-invaded range for all species; and environmental non-equilibrium in the native range or adaptive changes post-introduction for all species exceptH. erythraea. Niche changes undermined the reciprocal transferability of ENMs calibrated using native and Philippine-invaded range data. Our paper highlights the difficulty of predicting potential distributions given niche shifts and environmental non-equilibrium; we suggest calibrating ENMs with data from species’ combined native and invaded ranges, and to regularly reassess niche changes and recalibrate ENMs as species’ invasions progress.
Mesoscale computational protocols for the design of highly cooperative bivalent macromolecules
Authors: Saurabh Suman , Piazza Francesco
Published: May 2020

The last decade has witnessed a swiftly increasing interest in the design and production of novel multivalent molecules as powerful alternatives for conventional antibodies in the fight against cancer and infectious diseases. However, while it is widely accepted that large-scale flexibility (10–100 nm) and free/constrained dynamics (100 ns -μs) control the activity of such novel molecules, computational strategies at the mesoscale still lag behind experiments in optimizing the design of crucial features, such as the binding cooperativity (a.k.a. avidity). In this study, we introduced different coarse-grained models of a polymer-linked, two-nanobody composite molecule, with the aim of laying down the physical bases of a thorough computational drug design protocol at the mesoscale. We show that the calculation of suitable potentials of mean force allows one to apprehend the nature, range and strength of the thermodynamic forces that govern the motion of free and wall-tethered molecules. Furthermore, we develop a simple computational strategy to quantify the encounter/dissociation dynamics between the free end of a wall-tethered molecule and the surface, at the roots of binding cooperativity. This procedure allows one to pinpoint the role of internal flexibility and weak non-specific interactions on the kinetic constants of the nanobody-wall encounter and dissociation. Finally, we quantify the role and weight of rare events, which are expected to play a major role in real-life situations, such as in the immune synapse, where the binding kinetics is likely dominated by fluctuations.
Identifying trade-offs between biodiversity conservation and ecosystem services delivery for land-use decisions
Authors: Fastré Constance , Possingham Hugh P. , Strubbe Diederik , Matthysen Erik
Published: May 2020

Sustainable land-use management must account for the potential trade-offs between biodiversity conservation, productive land uses and ecosystem services. In this study, we used Marxan with Zones to generate land use plans that optimize conservation, farming and forestry land uses to reach biodiversity targets while minimizing the opportunity cost for local communities in an inhabited but data-poor National Park in the Andes of Bolivia. Based on six alternative land-use plans, we identified the synergies and trade-offs between the biodiversity benefits achieved in the different plans and the delivery of four locally important water-related ecosystem services modeled with the web-based tool AguAAndes. Although we find synergies between the conservation of high altitudePolylepiswoodlands and their associated avifauna and three of the ecosystem services investigated, soil erosion levels were actually higher in scenarios with higher achieved biodiversity benefits. Our study shows how systematic conservation planning and ecosystem service delivery modelling can be used to solve land-use conflicts and identify trade-offs between biodiversity conservation and ecosystem services in a data-poor tropical area.
Prostaglandin F2α agonist-induced suppression of 3T3-L1 cell adipogenesis affects spatial formation of extra-cellular matrix
Authors: Ida Yosuke , Hikage Fumihito , Itoh Kaku , Ida Haruka , Ohguro Hiroshi
Published: May 2020

To establish a deepening of the upper eyelid sulcus (DUES) model that can be induced by prostaglandin (PG) analogues, a three-dimension (3D) tissue culture was employed. Upon adipogenesis of the 3T3-L1 organoid, the effects of either Bimatoprost acid (BIM-A), or PGF2α were examined. During the adipogenesis, organoid size, lipid staining by BODIPY and expression of the extracellular matrix (ECM) by immunocytochemistry and/or quantitative PCR were employed. The size of the organoid increased remarkably during the adipogenesis, while such increases were significantly inhibited by the presence of PGF2α or BIM-A. BODIPY positive lipid-laden cells significantly increased during the adipogenesis, while in contrast they were greatly suppressed by the presence of PGF2α. Characteristic and spatial changes in ECM expressions observed upon adipogenesis were greatly modified by the presence of PGs. Our present study using a 3D tissue culture may be a suitable strategy toward understanding disease etiology of DUES.