bluuebunny/crossref_metadata_2025 huggingface dataset:
Modulation of forced isotropic turbulence by an anchored droplet with near-Kolmogorov diameter and varying volatility
Authors: Verwey C. , Birouk M.
Published: June 2023

Utilizing a fan-stirred chamber and two-dimensional particle image velocimetry, we analyse the modification of homogeneous and isotropic turbulence (

$50 \leq Re_\lambda \leq 140$

, with supplementary data out to

$Re_\lambda = 310$

, where

$Re_\lambda$

is the longitudinal Taylor Reynolds number) induced by both a non-volatile (water) and a volatile (ethanol) isolated and anchored droplet in the range

$(0.3 \leq d/\eta \leq 5.1)$

, where

$d/\eta$

is the ratio of droplet diameter to the Kolmogorov length scale. The dissipation rate,

$\varepsilon$

, is calculated via the corrected spatial gradient method, and the resultant fields of both turbulent kinetic energy,

$k$

, and

$\varepsilon$

are presented as spatial heat maps and as shell averages,

${\overline {k_{\Delta r}}}$

and

${\overline {\varepsilon _{\Delta r}}}$

, vs the radial coordinate normalized by the droplet radius,

$r/R$

. The dissipation rate near the water droplet surface may exceed the corresponding unladen flow value by a factor of twenty or more. The normalized radius of recovery,

$r^*$

, which designates the radial location where

${\overline {k_{\Delta r}}}$

or

${\overline {\varepsilon _{\Delta r}}}$

has returned to within 10 % of the unladen value, is reasonably expressed as

$r^* \propto (d/\lambda )^{-C_2}$

in either case, where

$\lambda$

is the longitudinal Taylor microscale and

$C_2$

is a positive empirical fitting parameter. Recovery of

${\overline {k_{\Delta r}}}$

and

${\overline {\varepsilon _{\Delta r}}}$

may take up to 14 normalized radii when

$d/\lambda$

is small. Trend line extrapolation suggests that the attenuation region becomes negligible as

$d/\lambda \to 1$

. Ethanol, which evaporates up to five times faster than water, induces a much smaller dissipation spike near the surface. The mass ejection phenomenon appears to reduce the strong near-surface damping of the radial root-mean-square component. However, the radius of recovery trend for fields surrounding a volatile ethanol droplet falls directly in line with the non-volatile water droplet data for both

$k$

and

$\varepsilon$

, indicating that droplet vaporization has little effect on the far-field return to isotropy.
Numerical analyses of wire-plate electrohydrodynamic flows
Authors: He Xuerao , Vázquez Pedro A. , Zhang Mengqi
Published: June 2023

We present numerical analyses of two-dimensional electrohydrodynamic (EHD) flows of a dielectric liquid between a wire electrode and two plate electrodes with a Poiseuille flow, using direct numerical simulation and global stability analysis. Both conduction and injection mechanisms for charge generation are considered. In this work we focused on the intensity of the cross-flow and studied the EHD flows without a cross-flow, with a weak cross-flow and with a strong cross-flow. (1) In the case without a cross-flow, we investigated its nonlinear flow structures and linear dynamics. We found that the flow in the conduction regime is steady, whereas the flow in the injection regime is oscillatory, which can be explained by a global stability analysis. (2) The EHD flow with a weak cross-flow is closely related to the flow phenomena in an electrostatic precipitator (ESP). Our analyses indicate that increasing the cross-flow intensity or the electric Reynolds number leads to a less stable flow. Based on these results, we infer that one should adopt a relatively low voltage and weak cross-flow in the wire-plate EHD flow to avoid flow instability, which may hold practical implications for ESP. (3) The case of strong cross-flow is examined to study the EHD effect on the wake flow. By comparing the conventional cylindrical wake with the EHD wake in linear and nonlinear regimes, we found that the EHD effect brings forward the vortex shedding in wake flows. Besides, the EHD effect reduces the drag coefficient when the cross-flow is weak, but increases it when it is strong.
Evaluation of the Uniform Data Set version 3 teleneuropsychological measures
Authors: Gierzynski Theresa F. , Gregoire Allyson , Reader Jonathan M. , Pantis Rebecca , Campbell Stephen , Bhaumik Arijit , Rahman-Filipiak Annalise , Heidebrink Judith , Giordani Bruno , Paulson Henry , Hampstead Benjamin M.
Published: June 2023

Objective:

Few studies have evaluated in-home teleneuropsychological (teleNP) assessment and none, to our knowledge, has evaluated the National Alzheimer’s Coordinating Center’s (NACC) Uniform Data Set version 3 tele-adapted test battery (UDS v3.0 t-cog). The current study evaluates the reliability of the in-home UDS v3.0 t-cog with a prior in-person UDS v3.0 evaluation.

Method:

One hundred and eighty-one cognitively unimpaired or cognitively impaired participants from a longitudinal study of memory and aging completed an in-person UDS v3.0 and a subsequent UDS v3.0 t-cog evaluation (∼16 months apart) administered either via video conference (n = 122) or telephone (n = 59).

Results:

We calculated intraclass correlation coefficients (ICCs) between each time point for the entire sample. ICCs ranged widely (0.01–0.79) but were generally indicative of “moderate” (i.e., ICCs ranging from 0.5–0.75) to “good” (i.e., ICCs ranging from 0.75–0.90) agreement. Comparable ICCs were evident when looking only at those with stable diagnoses. However, relatively stronger ICCs (Range: 0.35–0.87) were found between similarly timed in-person UDS v3.0 evaluations.

Conclusions:

Our findings suggest that most tests on the UDS v3.0 t-cog battery may serve as a viable alternative to its in-person counterpart, though reliability may be attenuated relative to the traditional in-person format. More tightly controlled studies are needed to better establish the reliability of these measures.
Obese mothers supplemented with melatonin during gestation and lactation ameliorate the male offspring’s pancreatic islet cellular composition and beta-cell function
Authors: Nagagata Brenda A. , Ajackson Matheus , Ornellas Fernanda , Mandarim-de-Lacerda Carlos A. , Aguila Marcia Barbosa
Published: June 2023

Melatonin supplementation to obese mothers during gestation and lactation might benefit the pancreatic islet cellular composition and beta-cell function in male offspring adulthood. C57BL/6 females (mothers) were assigned to two groups (n= 20/each) based on their consumption in control (C 17% kJ as fat) or high-fat diet (HF 49% kJ as fat). Mothers were supplemented with melatonin (Mel) (10 mg/kg daily) during gestation and lactation, or vehicle, forming the groups (n= 10/each): C, CMel, HF, and HFMel. The male offspring were studied, considering they only received the C diet after weaning until three months old. The HF mothers and their offspring showed higher body weight, glucose intolerance, insulin resistance, and low insulin sensitivity than the C ones. However, HFMel mothers and their offspring showed improved glucose metabolism and weight loss than the HF ones. Also, the offspring’s higher expressions of pro-inflammatory markers and endoplasmic reticulum (ER) stress were observed in HF but reduced in HFMel. Contrarily, antioxidant enzymes were less expressed in HF but improved in HFMel. In addition, HF showed increased beta-cell mass and hyperinsulinemia but diminished in HFMel. Besides, the beta-cell maturity and identity gene expressions diminished in HF but enhanced in HFMel. In conclusion, obese mothers supplemented with melatonin benefit their offspring’s islet cell remodeling and function. In addition, improving pro-inflammatory markers, oxidative stress, and ER stress resulted in better glucose and insulin levels control. Consequently, pancreatic islets and functioning beta cells were preserved in the offspring of obese mothers supplemented with melatonin.
Youth Depression Symptoms During COVID-19
Authors: Deppe Marco , Zapko-Willmes Alexandra
Published: June 2023

Abstract: The COVID-19 pandemic has induced new and exacerbated existing stressors. From a resilience framework perspective, we investigated which potentially protective individual and family factors are negatively associated with youth depression symptoms (DS) during COVID-19 and to what extent these associations are attributable to genetic and environmental factors. We considered 3,025 monozygotic and dizygotic twins in their adolescence and early adulthood from a representative German twin family sample. Multiple regression models yielded significant effects of prepandemic DS, life satisfaction, openness to experience, and internalizing behavior. We found a substantially smaller explanatory power of the considered predictors for pandemic compared to prepandemic DS. Twin analyses showed major time-specific environmental effects. Genetic variance was fully explained by prepandemic DS, life satisfaction, openness to experience, and internalizing behavior. Consecutive increases in explanatory power across pandemic waves point toward plasticity. The findings are discussed regarding the specificity of the pandemic and the importance of individual social settings in adaptation to pandemic adversity.
A Stranger or a Friend?
Authors: Lalot Fanny , Abrams Dominic
Published: June 2023

Abstract: A growing volume of work suggests a positive impact of descriptive norms on health-protective behavior in the COVID-19 pandemic. However, past work has often been correlational and has rarely compared the effect of different group norms. In the present paper, we present the results of a longitudinal study ( N = 1,051) that addresses these gaps by testing the cross-sectional and cross-lagged effects of norms and directly compared three different norms (close circle, neighborhood, and country) on compliance with COVID-19 regulations. The results revealed a positive effect of the close-circle norm (associated with more compliant behavior both cross-sectionally and longitudinally), no effect of the neighborhood norm, and a negative effect of the national norm (associated with less compliant behavior). Compliant behavior also led to a greater close-circle norm longitudinally, suggesting that both feed into each other. We discuss not only the challenges but also the chances this research highlights for norm-based interventions.
Predicting Real Refractive Index of Organic Aerosols From Elemental Composition
Authors: Li Yaowei , Bai Bin , Dykema John , Shin Nara , Lambe Andrew T. , Chen Qi , Kuwata Mikinori , Ng Nga Lee , Keutsch Frank N. , Liu Pengfei
Published: June 2023

Accurate estimates of aerosol refractive index (RI) are critical for modeling aerosol‐radiation interaction, yet this information is limited for ambient organic aerosols, leading to large uncertainties in estimating aerosol radiative effects. We present a semi‐empirical model that predicts the real RI n of organic aerosol material from its widely measured oxygen‐to‐carbon (O:C) and hydrogen‐to‐carbon (H:C) elemental ratios. The model was based on the theoretical framework of Lorenz‐Lorentz equation and trained with n‐values at 589 nm () of 160 pure compounds. The predictions can be expanded to predict n‐values in a wide spectrum between 300 and 1,200 nm. The model was validated with newly measured and literature datasets of n‐values for laboratory secondary organic aerosol (SOA) materials. Uncertainties of predictions for all SOA samples are within 5%. The model suggests that ‐values of organic aerosols may vary within a relatively small range for typical O:C and H:C values observed in the atmosphere.
Inferring Ocean Transport Statistics With Probabilistic Neural Networks
Authors: Brolly Martin T.
Published: June 2023

Using a probabilistic neural network and Lagrangian observations from the Global Drifter Program, we model the single particle transition probability density function (pdf) of ocean surface drifters. The transition pdf is represented by a Gaussian mixture whose parameters (weights, means, and covariances) are continuous functions of latitude and longitude determined to maximize the likelihood of observed drifter trajectories. This provides a comprehensive description of drifter dynamics allowing for the simulation of drifter trajectories and the estimation of a wealth of dynamical statistics without the need to revisit the raw data. As examples, we compute global estimates of mean displacements over 4 days and lateral diffusivity. We use a probabilistic scoring rule to compare our model to commonly used transition matrix models. Our model outperforms others globally and in three specific regions. A drifter release experiment simulated using our model shows the emergence of concentrated clusters in the subtropical gyres, in agreement with previous studies on the formation of garbage patches. An advantage of the neural network model is that it provides a continuous‐in‐space representation and avoids the need to discretize space, overcoming the challenges of dealing with nonuniform data. Our approach, which embraces data‐driven probabilistic modeling, is applicable to many other problems in fluid dynamics and oceanography.
SOX1 acts as a tumor hypnotist rendering nasopharyngeal carcinoma cells refractory to chemotherapy
Authors: Lei Xin-Xing , Wang Shu-Lan , Xia Ying , Yan Min , He Bin , Wang Bo , Long Zi-Jie , Liu Quentin
Published: June 2023

SOX1, a well-known tumor suppressor, delays malignant progression in most cancer types. However, high expression of SOX1 in late-stage head and neck squamous cell carcinoma leads to poor prognosis. In this study, we show that SOX1 induces nasopharyngeal carcinoma (NPC) cells to enter a quiescent state. Using a model that mimics therapeutic resistance and tumor recurrence, a subpopulation of SOX1-induced NPC cells is refractory to paclitaxel, a cell cycle-specific chemotherapy drug. These cells maintain a quiescent state with decreased translational activity and down-regulated cell growth potential. However, once SOX1 expression is decreased, the NPC cells recover and enter a proliferative state. The chemotherapy resistance induced by SOX1 can not pass to next generation, as the cells that undergo re-proliferation become sensitive to paclitaxel again. Moreover, SOX1 directly binds to the promoter region of the MYC gene, leading to transcriptional suppression. When switching to a paclitaxel-free culture environment, the cells with decreased levels of SOX1 re-express MYC, resulting in increased abundance of proliferative cancer cells. Our study presents an evolutionary trade-off between tumor growth and chemoresistance orchestrated by SOX1-MYC in NPC. Basing on the dynamic role of SOX1 in different stages of cancer development, SOX1 would be regarded as a “tumor hypnotist”.
Elucidating causative gene variants in hereditary Parkinson’s disease in the Global Parkinson’s Genetics Program (GP2)
Authors: Lange Lara M. , Avenali Micol , Ellis Melina , Illarionova Anastasia , Keller Sarmiento Ignacio J. , Tan Ai-Huey , Madoev Harutyun , Galandra Caterina , Junker Johanna , Roopnarain Karisha , Solle Justin , Wegel Claire , Fang Zih-Hua , Heutink Peter , Kumar Kishore R. , Lim Shen-Yang , Valente Enza Maria , Nalls Mike , Blauwendraat Cornelis , Singleton Andrew , Mencacci Niccolo , Lohmann Katja , Klein Christine ,   the Global Parkinson’s Genetic Program (GP2)
Published: June 2023

The Monogenic Network of the Global Parkinson’s Genetics Program (GP2) aims to create an efficient infrastructure to accelerate the identification of novel genetic causes of Parkinson’s disease (PD) and to improve our understanding of already identified genetic causes, such as reduced penetrance and variable clinical expressivity of known disease-causing variants. We aim to perform short- and long-read whole-genome sequencing for up to 10,000 patients with parkinsonism. Important features of this project are global involvement and focusing on historically underrepresented populations.
Tween emulsifiers improved alginate-based dispersions and ionic crosslinked milli-sized capsules
Authors: Zheng Yulu , Zi Ye , Shi Cuiping , Gong Huan , Zhang Hongbin , Wang Xichang , Zhong Jian
Published: June 2023

The blending of surfactants might change the properties of alginate-based oil encapsulation preparations. Herein, the effects of Tween series (Tween 20, 40, 60, and 80) blending on the fish oil-encapsulated sodium alginate dispersions and calcium alginate capsules were studied. The results suggested Tween 80 showed better emulsifying properties than Span 80 for the alginate/surfactant emulsions. All the Tween series induced higher creaming stability than the sodium alginate-stabilized dispersion. Tween series blending did not change the sizes, decreased the water contents, and induced similar particle-like protrusions of calcium alginate capsules. Loading capacity and encapsulation efficiency of fish oil were dependent on the hydrophilic heads and fatty acid moieties of the Tween series. Tween series blending could increase the fish oil oxidative stability of the capsules. In the in vitro digestion process, Tween with saturated fatty acid moieties increased the free fatty acid release percentages. This work provided potential innovative processing technologies for improving the biological potency of fish oil.
Knee flexion of saxophone players anticipates tonal context of music
Authors: Moura Nádia , Vidal Marc , Aguilera Ana M. , Vilas-Boas João Paulo , Serra Sofia , Leman Marc
Published: June 2023

Music performance requires high levels of motor control. Professional musicians use body movements not only to accomplish and help technical efficiency, but to shape expressive interpretation. Here, we recorded motion and audio data of twenty participants performing four musical fragments varying in the degree of technical difficulty to analyze how knee flexion is employed by expert saxophone players. Using a computational model of the auditory periphery, we extracted emergent acoustical properties of sound to inference critical cognitive patterns of music processing and relate them to motion data. Results showed that knee flexion is causally linked to tone expectations and correlated to rhythmical density, suggesting that this gesture is associated with expressive and facilitative purposes. Furthermore, when instructed to play immobile, participants tended to microflex (>1 Hz) more frequently compared to when playing expressively, possibly indicating a natural urge to move to the music. These results underline the robustness of body movement in musical performance, providing valuable insights for the understanding of communicative processes, and development of motor learning cues.
A chimeric vaccine protects farmed saltwater crocodiles from West Nile virus-induced skin lesions
Authors: Habarugira Gervais , Harrison Jessica J. , Moran Jasmin , Suen Willy W. , Colmant Agathe M. G. , Hobson-Peters Jody , Isberg Sally R. , Bielefeldt-Ohmann Helle , Hall Roy A.
Published: June 2023

West Nile virus (WNV) causes skin lesions in farmed crocodiles leading to the depreciation of the value of their hides and significant economic losses. However, there is no commercially available vaccine designed for use in crocodilians against WNV. We tested chimeric virus vaccines composed of the non-structural genes of the insect-specific flavivirus Binjari virus (BinJV) and genes encoding the structural proteins of WNV. The BinJV/WNV chimera, is antigenically similar to wild-type WNV but replication-defective in vertebrates. Intramuscular injection of two doses of BinJV/WNV in hatchling saltwater crocodiles (Crocodylus porosus) elicited a robust neutralising antibody response and conferred protection against viremia and skin lesions after challenge with WNV. In contrast, mock-vaccinated crocodiles became viraemic and 22.2% exhibited WNV-induced lesions. This suggests that the BinJV/WNV chimera is a safe and efficacious vaccine for preventing WNV-induced skin lesions in farmed crocodilians.
Self-patterning of human stem cells into post-implantation lineages
Authors: Pedroza Monique , Gassaloglu Seher Ipek , Dias Nicolas , Zhong Liangwen , Hou Tien-Chi Jason , Kretzmer Helene , Smith Zachary D. , Sozen Berna
Published: June 2023

Investigating human development is a substantial scientific challenge due to the technical and ethical limitations of working with embryonic samples. In the face of these difficulties, stem cells have provided an alternative to experimentally model inaccessible stages of human development in vitro1–13. Here we show that human pluripotent stem cells can be triggered to self-organize into three-dimensional structures that recapitulate some key spatiotemporal events of early human post-implantation embryonic development. Our system reproducibly captures spontaneous differentiation and co-development of embryonic epiblast-like and extra-embryonic hypoblast-like lineages, establishes key signalling hubs with secreted modulators and undergoes symmetry breaking-like events. Single-cell transcriptomics confirms differentiation into diverse cell states of the perigastrulating human embryo14,15 without establishing placental cell types, including signatures of post-implantation epiblast, amniotic ectoderm, primitive streak, mesoderm, early extra-embryonic endoderm, as well as initial yolk sac induction. Collectively, our system captures key features of human embryonic development spanning from Carnegie stage16 4–7, offering a reproducible, tractable and scalable experimental platform to understand the basic cellular and molecular mechanisms that underlie human development, including new opportunities to dissect congenital pathologies with high throughput.
Pluripotent stem cell-derived model of the post-implantation human embryo
Authors: Weatherbee Bailey A. T. , Gantner Carlos W. , Iwamoto-Stohl Lisa K. , Daza Riza M. , Hamazaki Nobuhiko , Shendure Jay , Zernicka-Goetz Magdalena
Published: June 2023

The human embryo undergoes morphogenetic transformations following implantation into the uterus, but our knowledge of this crucial stage is limited by the inability to observe the embryo in vivo. Models of the embryo derived from stem cells are important tools for interrogating developmental events and tissue–tissue crosstalk during these stages1. Here we establish a model of the human post-implantation embryo, a human embryoid, comprising embryonic and extraembryonic tissues. We combine two types of extraembryonic-like cell generated by overexpression of transcription factors with wild-type embryonic stem cells and promote their self-organization into structures that mimic several aspects of the post-implantation human embryo. These self-organized aggregates contain a pluripotent epiblast-like domain surrounded by extraembryonic-like tissues. Our functional studies demonstrate that the epiblast-like domain robustly differentiates into amnion, extraembryonic mesenchyme and primordial germ cell-like cells in response to bone morphogenetic protein cues. In addition, we identify an inhibitory role for SOX17 in the specification of anterior hypoblast-like cells2. Modulation of the subpopulations in the hypoblast-like compartment demonstrates that extraembryonic-like cells influence epiblast-like domain differentiation, highlighting functional tissue–tissue crosstalk. In conclusion, we present a modular, tractable, integrated3 model of the human embryo that will enable us to probe key questions of human post-implantation development, a critical window during which substantial numbers of pregnancies fail.
Effects of porous structure on the deformation failure mechanism of cement sheaths for wellbores
Authors: Yang Yongming , Li Xiwen , Sun Mengke , Ju Yang
Published: June 2023

The influence and mechanism of porous structure on the deformation failure of cement sheaths under hydraulic pressure is still unclear. To solve this problem, a net slurry cement sheath and a liquid silicon cement sheath were prepared by using a cement material and a liquid silicon suspension. The distributions of the pore radius and spatial location were analyzed using computed tomography scanning and statistics to obtain their probability density distribution functions. Based on the distribution functions, the single-layer and double-layer porous reconstruction models of the net slurry cement sheath and liquid silicon cement sheath were constructed using a FLAC 3D program. A series of numerical simulations were conducted to study the deformation failure of the cement sheaths under in situ stress and hydraulic pressure. The effects of the porous and double-layer structures on the breakdown pressure, plastic failure zone, radial deformation, and stress distribution of the cement sheaths were analyzed. As a result, the mechanisms for the influence of the porous and double-layer structures on the failure mode, failure path, and interaction between the cement sheath and metal casing were revealed. The results of this research provide a theoretical basis for an in-depth understanding of the failure mechanisms of porous cement sheaths.
Detecting and characterizing special nuclear material for nuclear nonproliferation applications
Authors: Pozzi S. A. , He Z. , Hutchinson J. , Jovanovic I. , Lopez R. , Ogren K. , Nattress J. , Shy D. , Clarke S. D.
Published: June 2023

There is an urgent need for new, better instrumentation and techniques for detecting and characterizing special nuclear material (SNM), i.e., highly enriched uranium and plutonium. The development of improved instruments and techniques requires experiments performed with the SNM itself, which is of limited availability. This paper describes the findings of experiments performed at the National Criticality Experiments Research Center conducted using new instruments and techniques on unclassified, kg-quantity SNM objects. These experiments, performed in the framework of the Department of Energy, National Nuclear Security Administration Consortium for Monitoring, Technology, and Verification, focused on detecting, characterizing, and localizing SNM samples with masses ranging from 3.3 to 13.8 kg, including plutonium and highly enriched uranium using prototype detectors and techniques. The work demonstrates SNM detection and characterization using recently-developed prototype detection systems. Specifically, we present new results in passive detection and imaging of plutonium and uranium objects using gamma-ray and dual particle (fast neutron and gamma-ray) imaging. We also present a new analysis of the delayed neutron emissions during active interrogation of uranium using a neutron generator.
Drosophila mutants lacking the glial neurotransmitter-modifying enzyme Ebony exhibit low neurotransmitter levels and altered behavior
Authors: Pantalia Meghan , Lin Zhi , Tener Samantha J. , Qiao Bing , Tang Grace , Ulgherait Matthew , O’Connor Reed , Delventhal Rebecca , Volpi Julia , Syed Sheyum , Itzhak Nissim , Canman Julie C. , Fernández María Paz , Shirasu-Hiza Mimi
Published: June 2023

Inhibitors of enzymes that inactivate amine neurotransmitters (dopamine, serotonin), such as catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO), are thought to increase neurotransmitter levels and are widely used to treat Parkinson's disease and psychiatric disorders, yet the role of these enzymes in regulating behavior remains unclear. Here, we investigated the genetic loss of a similar enzyme in the model organism Drosophila melanogaster. Because the enzyme Ebony modifies and inactivates amine neurotransmitters, its loss is assumed to increase neurotransmitter levels, increasing behaviors such as aggression and courtship and decreasing sleep. Indeed, ebony mutants have been described since 1960 as "aggressive mutants," though this behavior has not been quantified. Using automated machine learning-based analyses, we quantitatively confirmed that ebony mutants exhibited increased aggressive behaviors such as boxing but also decreased courtship behaviors and increased sleep. Through tissue-specific knockdown, we found that ebony’s role in these behaviors was specific to glia. Unexpectedly, direct measurement of amine neurotransmitters in ebony brains revealed that their levels were not increased but reduced. Thus, increased aggression is the anomalous behavior for this neurotransmitter profile. We further found that ebony mutants exhibited increased aggression only when fighting each other, not when fighting wild-type controls. Moreover, fights between ebony mutants were less likely to end with a clear winner than fights between controls or fights between ebony mutants and controls. In ebony vs. control fights, ebony mutants were more likely to win. Together, these results suggest that ebony mutants exhibit prolonged aggressive behavior only in a specific context, with an equally dominant opponent.
Bedaquiline- and clofazimine- selected Mycobacterium tuberculosis mutants: further insights on resistance driven largely by Rv0678
Authors: Snobre J. , Villellas M. C. , Coeck N. , Mulders W. , Tzfadia O. , de Jong B. C. , Andries K. , Rigouts L.
Published: June 2023

Drug-resistant tuberculosis is a serious global health threat. Bedaquiline (BDQ) is a relatively new core drug, targeting the respiratory chain inMycobacterium tuberculosis(Mtb). While mutations in the BDQ target gene,atpE,are rare in clinical isolates, mutations in theRv0678gene, a transcriptional repressor regulating the efflux pump MmpS5-MmpL5,are increasingly observed, and have been linked to worse treatment outcomes. Nevertheless, underlying mechanisms of (cross)-resistance remain incompletely resolved. Our study aims to distinguish resistance associated variants from other polymorphisms, by assessing the in vitro onset of mutations under drug pressure, combined with their impact on minimum inhibitory concentrations (MICs) and on protein stability. For this purpose, isolates were exposed in vitro to sub-lethal concentrations of BDQ or clofazimine (CFZ). Selected colonies had BDQ- and CFZ-MICs determined on 7H10 and 7H11 agar. Sanger sequencing and additional Deeplex Myc-TB and whole genome sequencing (WGS) for a subset of isolates were used to search for mutations inRv0678, atpEandpepQ. In silico characterization of relevant mutations was performed using computational tools. We found that colonies that grew on BDQ medium had mutations inRv0678,atpEorpepQ, while CFZ-exposed isolates presented mutations inRv0678andpepQ, but none inatpE. Twenty-eightRv0678mutations had previously been described among in vitro selected mutants or in patients’ isolates, while 85 were new. Mutations were scattered across theRv0678gene without apparent hotspot. While mostRv0678mutations led to an increased BDQ- and/or CFZ-MIC, only a part of them surpassed the critical concentration (69.1% for BDQ and 87.9% for CFZ). Among the mutations leading to elevated MICs for BDQ and CFZ, we report a synonymous Val1Val mutation in theRv0678start codon. Finally,in silico characterization ofRv0678mutations suggests that especially the C46R mutant may renderRv0678less stable.
Comparing mechanism-based and machine learning models for predicting the effects of glucose accessibility on tumor cell proliferation
Authors: Yang Jianchen , Virostko Jack , Liu Junyan , Jarrett Angela M. , Hormuth David A. , Yankeelov Thomas E.
Published: June 2023

Glucose plays a central role in tumor metabolism and development and is a target for novel therapeutics. To characterize the response of cancer cells to blockade of glucose uptake, we collected time-resolved microscopy data to track the growth of MDA-MB-231 breast cancer cells. We then developed a mechanism-based, mathematical model to predict how a glucose transporter (GLUT1) inhibitor (Cytochalasin B) influences the growth of the MDA-MB-231 cells by limiting access to glucose. The model includes a parameter describing dose dependent inhibition to quantify both the total glucose level in the system and the glucose level accessible to the tumor cells. Four common machine learning models were also used to predict tumor cell growth. Both the mechanism-based and machine learning models were trained and validated, and the prediction error was evaluated by the coefficient of determination (R2). The random forest model provided the highest accuracy predicting cell dynamics (R2 = 0.92), followed by the decision tree (R2 = 0.89),k-nearest-neighbor regression (R2 = 0.84), mechanism-based (R2 = 0.77), and linear regression model (R2 = 0.69). Thus, the mechanism-based model has a predictive capability comparable to machine learning models with the added benefit of elucidating biological mechanisms.
Balance-energy of resting state network in obsessive-compulsive disorder
Authors: Talesh Alireza , Zarei Asghar , Yazdi-Ravandi Saeid , Ghaleiha Ali , Shamsaei Farshid , Matinnia Nasrin , Shams Jamal , Ahmadpanah Mohammad , Taslimi Zahra , Moghimbeigi Abbas , Khosrowabadi Reza
Published: June 2023

Stability of the brain functional network is directly linked to organization of synchronous and anti-synchronous activities. Nevertheless, impact of arrangement of positive and negative links called links topology requires to be well understood. In this study, we investigated how topology of the functional links reduce balance-energy of the brain network in obsessive-compulsive disorder (OCD) and push the network to a more stable state as compared to healthy controls. Therefore, functional associations between the regions were measured using the phase synchrony between the EEG activities. Subsequently, balance-energy of the brain functional network was estimated based on the quality of triadic interactions. Occurrence rates of four different types of triadic interactions including weak and strong balanced, and unbalanced interactions were compared. In addition, impact of the links topology was also investigated by looking at the tendency of positive and negative links to making hubs. Our results showed although the number of positive and negative links were not statistically different between OCD and healthy controls, but positive links in OCDs’ brain networks have more tendency to make hub. Moreover, lower number of unbalanced triads and higher number of strongly balanced triad reduced the balance-energy in OCDs’ brain networks that conceptually has less requirement to change. We hope these findings could shed a light on better understanding of brain functional network in OCD.
Machine learning-based somatic variant calling in cell-free DNA of metastatic breast cancer patients using large NGS panels
Authors: Jongbloed Elisabeth M. , Jansen Maurice P. H. M. , de Weerd Vanja , Helmijr Jean A. , Beaufort Corine M. , Reinders Marcel J. T. , van Marion Ronald , van IJcken Wilfred F. J. , Sonke Gabe S. , Konings Inge R. , Jager Agnes , Martens John W. M. , Wilting Saskia M. , Makrodimitris Stavros
Published: June 2023

Next generation sequencing of cell-free DNA (cfDNA) is a promising method for treatment monitoring and therapy selection in metastatic breast cancer (MBC). However, distinguishing tumor-specific variants from sequencing artefacts and germline variation with low false discovery rate is challenging when using large targeted sequencing panels covering many tumor suppressor genes. To address this, we built a machine learning model to remove false positive variant calls and augmented it with additional filters to ensure selection of tumor-derived variants. We used cfDNA of 70 MBC patients profiled with both the small targeted Oncomine breast panel (Thermofisher) and the much larger Qiaseq Human Breast Cancer Panel (Qiagen). The model was trained on the panels’ common regions using Oncomine hotspot mutations as ground truth. Applied to Qiaseq data, it achieved 35% sensitivity and 36% precision, outperforming basic filtering. For 20 patients we used germline DNA to filter for somatic variants and obtained 245 variants in total, while our model found seven variants, of which six were also detected using the germline strategy. In ten tumor-free individuals, our method detected in total one (potentially germline) variant, in contrast to 521 variants detected without our model. These results indicate that our model largely detects somatic variants.
The distinction between irritability and anger and their associations with impulsivity and subjective wellbeing
Authors: Gröndal Maria , Ask Karl , Winblad Stefan
Published: June 2023

Irritability, anger, and impulsivity have important associations with psychological well-being. However, studying the internal relationships between such emotional constructs is challenging, largely because of the lack of precise operational definitions and extensively validated measurement tools. The aim of this study was to examine relationships between the above emotional constructs and how they relate to satisfaction with life and perceived negative impact on different life domains. Participants (N = 471) completed a self-report questionnaire online. Correlational analyses showed that higher levels of irritability and trait anger were associated with lower life satisfaction. Impulsivity displayed complex relationships with life satisfaction, with some aspects (sensation seeking) showing a positive relationship and others (urgency, lack of perseverance) showing a negative relationship. A two-factor Confirmatory Factor Analysis treating irritability and anger as separate constructs showed a better fit compared with a one-factor model, indicating that irritability and anger should be treated as separate constructs. An exploratory moderation analysis showed that higher irritability predicted increased anger only for participants scoring average to high on urgency (a facet of impulsivity). Our findings increase the understanding of the relationship between these dispositional constructs and supports the conceptualization of irritability and anger as related but distinct constructs.
Multiple factors contribute to flight behaviors during fear conditioning
Authors: Furuyama Takafumi , Imayoshi Ayana , Iyobe Toyo , Ono Munenori , Ishikawa Tatsuya , Ozaki Noriyuki , Kato Nobuo , Yamamoto Ryo
Published: June 2023

Shifting defensive mode from one to another by the imminence of threat is crucial for survival. The transition of defensive mode from freezing to flight is observed during the modified fear conditioning, however, the flight during fear conditioning is not well characterized. To characterize the flight behaviors during the fear conditioning, we conducted experiments in male mice focusing on the influence of the context, the intensity of the unconditioned stimulus and conditioned stimulus (CS), the schedule of conditioning, and the state of the subject. Flight behaviors triggered by salient CS showed characteristics of fear-potentiated defensive behaviors depending on the conditioned context, while repetitive conditioning enhanced the expression of the flight and developed an association between the CS and the flight. The salient auditory stimulus was the primary factor to trigger flight behaviors. Also, the spaced conditioning increased the expression of flight behaviors. Taken together, the flight behavior during fear conditioning is not a simple conditioned response nor simple fear-potentiated behavior, but a complicated mixture of multiple components of defensive behaviors. The transition of defensive mode could be induced by the integration of multiple innate and learned components of fear or anxiety.
Significant contributions of trimethylamine to sulfuric acid nucleation in polluted environments
Authors: Cai Runlong , Yin Rujing , Li Xue , Xie Hong-Bin , Yang Dongsen , Kerminen Veli-Matti , Smith James N. , Ma Yan , Hao Jiming , Chen Jingwen , Kulmala Markku , Zheng Jun , Jiang Jingkun , Elm Jonas
Published: June 2023

As one of the least understood aerosol processes, nucleation can be a dominant source of atmospheric aerosols. Sulfuric acid (SA)-amine binary nucleation with dimethylamine (DMA) has been recognized as a governing mechanism in the polluted continental boundary layer. Here we demonstrate the importance of trimethylamine (TMA) for nucleation in the complex atmosphere and propose a molecular-level SA-DMA-TMA ternary nucleation mechanism as an improvement upon the conventional binary mechanism. Using the proposed mechanism, we could connect the gaseous amines to the SA-amine cluster signals measured in the atmosphere of urban Beijing. Results show that TMA can accelerate the SA-DMA-based new particle formation in Beijing by 50–100%. Considering the global abundance of TMA and DMA, our findings imply comparable importance of TMA and DMA to nucleation in the polluted continental boundary layer, with probably higher contributions from TMA in polluted rural environments and future urban environments with controlled DMA emissions.
MXene functionalized collagen biomaterials for cardiac tissue engineering driving iPSC-derived cardiomyocyte maturation
Authors: Asaro Giuseppe A. , Solazzo Matteo , Suku Meenakshi , Spurling Dahnan , Genoud Katelyn , Gonzalez Javier Gutierrez , Brien Fergal J. O’ , Nicolosi Valeria , Monaghan Michael G.
Published: June 2023

Electroconductive biomaterials are gaining significant consideration for regeneration in tissues where electrical functionality is of crucial importance, such as myocardium, neural, musculoskeletal, and bone tissue. In this work, conductive biohybrid platforms were engineered by blending collagen type I and 2D MXene (Ti3C2Tx) and afterwards covalently crosslinking; to harness the biofunctionality of the protein component and the increased stiffness and enhanced electrical conductivity (matching and even surpassing native tissues) that two-dimensional titanium carbide provides. These MXene platforms were highly biocompatible and resulted in increased proliferation and cell spreading when seeded with fibroblasts. Conversely, they limited bacterial attachment (Staphylococcus aureus) and proliferation. When neonatal rat cardiomyocytes (nrCMs) were cultured on the substrates increased spreading and viability up to day 7 were studied when compared to control collagen substrates. Human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) were seeded and stimulated using electric-field generation in a custom-made bioreactor. The combination of an electroconductive substrate with an external electrical field enhanced cell growth, and significantly increased cx43 expression. This in vitro study convincingly demonstrates the potential of this engineered conductive biohybrid platform for cardiac tissue regeneration.
Functionally analogous body- and animacy-responsive areas are present in the dog (Canis familiaris) and human occipito-temporal lobe
Authors: Boch Magdalena , Wagner Isabella C. , Karl Sabrina , Huber Ludwig , Lamm Claus
Published: June 2023

Comparing the neural correlates of socio-cognitive skills across species provides insights into the evolution of the social brain and has revealed face- and body-sensitive regions in the primate temporal lobe. Although from a different lineage, dogs share convergent visuo-cognitive skills with humans and a temporal lobe which evolved independently in carnivorans. We investigated the neural correlates of face and body perception in dogs (N = 15) and humans (N = 40) using functional MRI. Combining univariate and multivariate analysis approaches, we found functionally analogous occipito-temporal regions involved in the perception of animate entities and bodies in both species and face-sensitive regions in humans. Though unpredicted, we also observed neural representations of faces compared to inanimate objects, and dog compared to human bodies in dog olfactory regions. These findings shed light on the evolutionary foundations of human and dog social cognition and the predominant role of the temporal lobe.
Anomalous fractal scaling in two-dimensional electric networks
Authors: Zhang Xiao , Zhang Boxue , Sahin Haydar , Siu Zhuo Bin , Rafi-Ul-Islam S. M. , Kong Jian Feng , Shen Bing , Jalil Mansoor B. A. , Thomale Ronny , Lee Ching Hua
Published: June 2023

Much of the qualitative nature of physical systems can be predicted from the way it scales with system size. Contrary to the continuum expectation, we observe a profound deviation from logarithmic scaling in the impedance of a two-dimensional LC circuit network. We find this anomalous impedance contribution to sensitively depend on the number of nodes N in a curious erratic manner and experimentally demonstrate its robustness against perturbations from the contact and parasitic impedance of individual components. This impedance anomaly is traced back to a generalized resonance condition reminiscent of Harper’s equation for electronic lattice transport in a magnetic field, even though our circuit network does not involve magnetic translation symmetry. It exhibits an emergent fractal parametric structure of anomalous impedance peaks for different N that cannot be reconciled with a continuum theory and does not correspond to regular waveguide resonant behavior. This anomalous fractal scaling extends to the transport properties of generic systems described by a network Laplacian whenever a resonance frequency scale is simultaneously present.
Dual cascade nucleic acid recycling-amplified assembly of hyperbranched DNA nanostructures to construct a novel plasmonic colorimetric biosensing method
Authors: Yuwen Xinyue , Zeng Yingzhao , Ruan Shilong , Li Xin , Lai Guosong
Published: June 2023

The dual cascade nucleic acid recycling-amplified assembly of hyperbranched DNA nanostructures enables the successful construction of a novel gold nanobipyramids-based plasmonic colorimetric biosensing method for antibiotic assays.
Cell-type-specific CRISPRization of mitochondrial DNA using bifunctional biodegradable silica nanoparticles
Authors: Jiang Linye , Zhou Bizhong , Qian Huijuan , Wang Hongfeng , Wang Yuxi , Fan Weijiao , Zheng Guowan , Ge Jingyan
Published: June 2023

By using biodegradable silica nanoparticles (BSNPs) with surface-modified triphenylphosphonium (TPP) and hyaluronic acid (HA), we report CRISPR/Cas9-mediated cell-type-specific mtDNA editing.
Prediction of CO2 adsorption properties of azo, azoxy and azodioxy-linked porous organic polymers guided by electrostatic potential
Authors: Frey Tea , Panić Barbara , Šutalo Petar , Borovina Mladen , Biljan Ivana , Kodrin Ivan
Published: June 2023

CO2 adsorption properties of azo, azoxy and azodioxy-linked porous organic polymers can be predicted from the calculated electrostatic potential values.
Stability and activity of titanium oxynitride thin films for the electrocatalytic reduction of nitrogen to ammonia at different pH values
Authors: Chukwunenye Precious , Ganesan Ashwin , Gharaee Mojgan , Balogun Kabirat , Adesope Qasim , Amagbor Stella Chinelo , Golden Teresa D. , D’Souza Francis , Cundari Thomas R. , Kelber Jeffry A.
Published: June 2023

Experimental and computational activity and selectivity of sputter-deposited titanium nitride and titanium oxynitride films for nitrogen reduction and hydrogen evolution reactions at different pH values are reported.
Ferroelectric and strain-tuned MoSe2/Bi2O2Se van der Waals heterostructure with band alignment evolution
Authors: Lu Shucao , Li Yanlu , Zhao Xian
Published: June 2023

We theoretically propose a MoSe2/Bi2O2Se vdW heterostructure, whose band structure can be modulated within the unipolar barrier structure, type-I, and type-II by utilizing the ferroelectric polarization of Bi2O2Se and an in-plane biaxial strain.
Tuning the hardness and crack resistance through liquid–liquid phase separation in an aluminosilicate glass
Authors: Xia Feiyue , Wang Xiaowei , Wang Yadan , Ren Xiaoming , Qiao Ang , Tao Haizheng
Published: June 2023

We have revealed the microstructural origin about how liquid–liquid phase separation impacts the mechanical properties of 30Al2O3·70SiO2 aluminosilicate glass.
IR spectra and structures of saturated ruthenium cluster carbonyl cations Run(CO)m+ (n = 1–6)
Authors: Yubero Valdivielso David , Kerpal Christian , Schöllkopf Wieland , Meijer Gerard , Fielicke André
Published: June 2023

Infrared multiple photon dissociation spectroscopy using an IR free electron laser allows for structural elucidation of a series of cationic ruthenium cluster carbonyls.