bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of spanwise-periodic surface heating on supersonic boundary-layer instability
Authors: Zhu Kaixin , Wu Xuesong
Published: April 2022

The effects of streamwise-elongated, spanwise-periodic surface heating on a supersonic boundary-layer instability are investigated under the assumption of high Reynolds number. Our focus is on the lower-branch viscous instability and so the spanwise spacing of the elements is chosen to be of

$O({\textit {Re}}^{-3/8}L)$

, the wavelength of the latter, where

${\textit {Re}}$

is the Reynolds number based on

$L$

, the distance from the leading edge to the centre of the elements. The streamwise length is assumed to be much longer in order to simplify the mathematical description. Starting with classical triple-deck theory, the equations governing the heating-induced streaky flow are derived by appropriate rescaling. When Chapman's viscosity law is adopted, a similarity solution is found. The stability of the streaky flow, which is of a bi-global nature, is shown to be governed by a novel triple-deck structure characterised by fully compressible dynamics in the lower deck. Through asymptotic analysis, the bi-global stability is reduced to a one-dimensional eigenvalue problem, which involves only the spanwise-dependent wall temperature and wall shear. The instability modes may be viewed as a continuation of oncoming first Mack modes, but might also be considered as a new kind since they exhibit two distinctive features: strong temperature perturbation near the wall and spontaneous radiation of an acoustic wave to the far field, neither of which is shared by first Mack modes. Numerical calculations, performed for two simple patterns of spanwise-periodic heating elements, demonstrate their stabilising/destabiling effects on modes with different frequencies and spanwise wavelengths.
Topological bifurcations in the transition from two single vortices to a pair and a single vortex in the periodic wake behind an oscillating cylinder
Authors: Nielsen Anne R. , Matharu Puneet S. , Brøns Morten
Published: April 2022

We explore the two-dimensional flow past a cylinder undergoing forced transversal oscillations with the aim of elucidating the evolution of the topology of the wake under variation of the forcing amplitude at a Reynolds number of 100. In particular, we study the change from two single vortices (2S mode) to a pair and a single vortex (

$\text {P}+ \text {S}$

mode) being shed per period. Matharu et al. (J. Fluid Mech., vol. 918, 2021, p. A21) showed that a dynamical symmetry-breaking pitchfork bifurcation plays a key role in this transition. We show that in addition to this bifurcation, a number of topological bifurcations in the vorticity field occur, both on the symmetric 2S branch and on the asymmetric

$\text {P}+ \text {S}$

branch. The topological bifurcations are cusp bifurcations where an extremum of vorticity is created or destroyed. To describe the effect of the topological bifurcations we introduce an extended symbolic classification of the wake modes to account for the spatial variations of the vortex patterns that occur in the transition process. We identify four amplitude values that define critical stages in the transition, and provide a complete qualitative picture of the transition from 2S to

$\text {P}+ \text {S}$

mode. We confirm the robustness of the observed transition process by simulations at Reynolds number 80.
Interaction between near-wall streaks and large-scale motions in turbulent channel flows
Authors: Zhou Zisong , Xu Chun-Xiao , Jiménez Javier
Published: April 2022

The interactions between the near-wall streaks and the large-scale motions (LSMs) of the outer region of wall-bounded turbulent flows are investigated. The co-supporting hypothesis of Toh & Itano (J. Fluid Mech., vol. 524, 2005, pp. 249–262) is checked in full-scale channels at low to moderate Reynolds numbers, from two points of view. To study the top-down influence of the outer structures on the spanwise motion of the near-wall streaks, a method inspired by particle-image velocimetry is used to track the spanwise position of the streaks. Their spanwise advection velocity is found to be affected by the hierarchy of large-scale circulations in the logarithmic layer, but their spanwise streak density is only weakly related to the LSMs. The evidence suggests that a top-down influence exists and drives the drift of the streaks in the spanwise direction, as suggested by Toh & Itano (J. Fluid Mech., vol. 524, 2005, pp. 249–262), but that the hypothesised streak accumulation rarely occurs. Numerical experiments at

$Re_{\tau }\thickapprox 535$

are then performed to clarify the role of the near-wall streaks in the generation and preservation of the outer LSMs. The results show that the merger of the near-wall streaks is only weakly correlated with the generation of the LSMs, and that removing the near-wall roots of the LSMs does not affect the evolution of their outer region. It is concluded that the bottom-up influence from the near-wall streaks is not essential for the LSM generation and preservation, also weakening the evidence for the co-supporting hypothesis.
Phoretic self-propulsion of a slightly inhomogeneous disc
Authors: Saha S. , Yariv E.
Published: April 2022

In two dimensions, the problem governing a homogeneous phoretic swimmer of circular cross-section is ill-posed because of the logarithmic divergence associated with a purely diffusive solute transport. We address here the well-posed problem that is devised by introducing a slight inhomogeneity in the interfacial chemical activity. With the radial symmetry being perturbed, phoretic motion is animated by diffusio-osmosis. Solute advection, associated with that motion, becomes comparable to diffusion at large distances. The singular problem associated with that scale disparity is analysed using matched asymptotic expansions for arbitrary values of the Damköhler number

$\textit {Da}$

and the intrinsic Péclet number

$\textit {Pe}$

. Asymptotic matching provides an implicit equation for the particle velocity in terms of these two parameters. The velocity exhibits a non-trivial dependence upon the sign

$M$

of the slip coefficient. For

$M=-1$

, we observe the appearance of several solutions beyond a

$\textit {Da}$

-dependent critical value of

$\textit {Pe}$

. We also address the respective limits of small and large

$\textit {Da}$

for fixed

$\textit {Pe}$

and arbitrary inhomogeneity, and illuminate their linkage to the limit of weak inhomogeneity.
A new equivalent sand grain roughness relation for two-dimensional rough wall turbulent boundary layers
Authors: Abdelaziz Misarah , Djenidi L. , Ghayesh Mergen H. , Chin Rey
Published: April 2022

The effects of different geometries of two-dimensional (2-D) roughness elements in a zero pressure gradient (ZPG) turbulent boundary layer (TBL) on turbulence statistics and drag coefficient are assessed using single hot-wire anemometry. Three kinds of 2-D roughness are used: (i) circular rods with two different heights,

$k= 1.6$

and 2.4 mm, and five different streamwise spacing of

$s_{x}= 6k$

to

$24k$

, (ii) three-dimensional (3-D) printed triangular ribs with heights of

$k= 1.6$

mm and spacing of

$s_{x}= 8k$

and (iii) computerized numerical control (CNC) machined sinewave surfaces with two different heights,

$k= 1.6$

and 2.4 mm, and spacing of

$s_{x}= 8k$

. These roughnesses cover a wide range of ratios of the boundary layer thickness to the roughness height (

$23 < \delta /k < 41$

), where

$\delta$

is the boundary layer thickness. All roughnesses cause a downward shift on the wall-unit normalised streamwise mean velocity profile when compared with the smooth wall profiles agreeing with the literature, with a maximum downward shift observed for

$s_{x}= 8k$

. In the fully rough regime, the drag coefficient becomes independent of the Reynolds number. Changing the roughness height while maintaining the same spacing ratio

$s_{x}/k$

exhibits little influence on the drag coefficient in the fully rough regime. On the other hand, the effective slope

$(ES)$

and the height skewness

$(k_{sk})$

appear to be major surface roughness parameters that affect the drag coefficient. These parameters are used in a new expression for

$k_{s}$

, the equivalent sand grain roughness, developed for 2-D uniformly distributed roughness in the fully rough regime.
Ritual cursing as an oath of submission: The problem of religious difference across Safavid Iran and modern Pakistan
Authors: Saeed Sadia
Published: April 2022

This article undertakes a comparison between Safavid Iran and modern Pakistan with the aim of highlighting the similarities and differences between their respective state projects of crafting ‘Islamic’ polities. The comparison proceeds through a focus on the state-sanctioned practice of ritual cursing of Sunnis and Ahmadis in Safavid Iran and Pakistan respectively. In both cases, the states made extensive legal efforts to mark out these religious Others by vilifying them on charges of heresy and innovation. This article argues that this vilification was oriented towards creating homogeneity among political subjects of the polity, who were required by the state to curse and condemn these religious Others in order to demonstrate their submission to sovereign power. Ritual cursing thus functioned as an oath of submission that was elicited by the state to draw subjects into the project of sacralizing the polity and to discipline them into reproducing the normative order of the sovereign power. There are also significant differences between the two cases that throw light on the historical specificity of different modes of sovereignty in early modern and modern Muslim polities. While Safavid kings sacralized their realm through the diffusion of scriptural law moulded to enhance their own sovereign power, the Pakistani state is engaged in the sacralization of the national body politic through its official religious nationalist ideology.
‘Rahman’ before Muhammad: A pre-history of the First Peace (Sulh) in Islam
Authors: Kjær Sigrid K.
Published: April 2022

This article examines how the divine epithet ‘Rahman’ was invoked in public inscriptions and oaths in pre-Islamic Yemen. Between the first and the sixth centuriesce, with the spread of Christianity across the Roman empire and Abyssinia, and the subsequent rise of Jewish and Christian kingdoms in southern Arabia, the use of ‘Rahman’ was gradually biblicized. By tracing this history, this article opens a window into the use of this theonym in the Quran and the controversy surrounding its use in the first formal treaty in Islam, the Peace Treaty (Sulh) of Hudaybiyya.
Effective connectivity during face processing in major depression – distinguishing markers of pathology, risk, and resilience
Authors: Sacu Seda , Wackerhagen Carolin , Erk Susanne , Romanczuk-Seiferth Nina , Schwarz Kristina , Schweiger Janina I. , Tost Heike , Meyer-Lindenberg Andreas , Heinz Andreas , Razi Adeel , Walter Henrik
Published: April 2022

Background

Aberrant brain connectivity during emotional processing, especially within the fronto-limbic pathway, is one of the hallmarks of major depressive disorder (MDD). However, the methodological heterogeneity of previous studies made it difficult to determine the functional and etiological implications of specific alterations in brain connectivity. We previously reported alterations in psychophysiological interaction measures during emotional face processing, distinguishing depressive pathology from at-risk/resilient and healthy states. Here, we extended these findings by effective connectivity analyses in the same sample to establish a refined neural model of emotion processing in depression.

Methods

Thirty-seven patients with MDD, 45 first-degree relatives of patients with MDD and 97 healthy controls performed a face-matching task during functional magnetic resonance imaging. We used dynamic causal modeling to estimate task-dependent effective connectivity at the subject level. Parametric empirical Bayes was performed to quantify group differences in effective connectivity.

Results

MDD patients showed decreased effective connectivity from the left amygdala and left lateral prefrontal cortex to the fusiform gyrus compared to relatives and controls, whereas patients and relatives showed decreased connectivity from the right orbitofrontal cortex to the left insula and from the left orbitofrontal cortex to the right fusiform gyrus compared to controls. Relatives showed increased connectivity from the anterior cingulate cortex to the left dorsolateral prefrontal cortex compared to patients and controls.

Conclusions

Our results suggest that the depressive state alters top-down control of higher visual regions during face processing. Alterations in connectivity within the cognitive control network present potential risk or resilience mechanisms.
About me, you and her: Personal pronouns are developmentally preceded by mental state language
Authors: SMOLÍK Filip , CHROMÁ Anna
Published: April 2022

Person-referring pronouns in the first and second person (I, your) have been viewed as signs of increasing social understanding in children due to their shifting reference properties. However, they are linguistically complex elements and might depend on general language development. We used longitudinal transcript data from Manchester corpus (12 children aged 2 to 3 years) to examine concurrent and predictive relations between pronouns, general language development (MLU), and social understanding (indexed by the use of mental state language). In the key analysis, social understanding but not general language was found to be a developmental precursor of first-, second- and third-person pronoun mastery. Results suggest that social understanding is needed for acquisition of all person reference, not only in first and second person. Results for first- and third-person pronouns were more similar than for second person, suggesting that social-cognitive demands of person reference go beyond shifting reference of first- and second-person.
Chemical Agent Use in Terrorist Events: A Gathering Storm Requiring Enhanced Civilian Preparedness
Authors: Tin Derrick , Ciottone Gregory R.
Published: April 2022

Background:

The use of chemical weapons in terrorist attacks, though rare, remains a significant challenge and concern due to their ability to inflict mass casualties. Chemical attacks remain a topic of interest for Disaster Medicine (DM) and Counter-Terrorism Medicine (CTM) specialists and are clearly an area in need of enhanced preparedness. This study aims to provide an epidemiological description of all terrorism-related attacks using chemical agents as a primary weapon, sustained from 1970 - 2019. These data will be useful in the development of education programs in CTM and provide an insight into how best to prepare for potential attacks in the future.

Methods:

Data collection was performed using a retrospective database search through the Global Terrorism Database (GTD). The GTD was searched using the internal database search functions for all events using chemical weapons as a primary attack method from January 1, 1970 - December 31, 2019. Years 2020 and 2021 were not yet available at the time of the study. The GTD also details the specific chemical used, when known, in the summary of incidents. Results were exported into an Excel spreadsheet (Microsoft Corp.; Redmond, Washington USA) for analysis.

Results:

A total of 292 terrorist attacks involving chemical agents as a primary attack method were recorded from 1970 - 2019, registering 284 deaths and 13,267 injuries. Acid (52) was the most commonly used chemical agent, followed by “unspecified poison” (43), “unknown chemical agents” (29), “unspecified gas” (27), tear gas (27), chlorine gas (24), cyanide (21), mercury (9), pepper spray or mace (9), mustard gas (8), insecticide or 1080 (8), diphenylamine chloroarsine (7), phosphate or phosphorous (3), sodium hydroxide or corrosive liquid (3), sarin (2), “unspecified drugs” (2), VX nerve gas and other nerve gas (2), pesticides (2), cleaning chemicals/paint thinner (2), ammonia (2), anesthesia agent (1), arsenic (1), chlorine and mustard gas mix (1), phenarsazine chloride (1), rat poison (1), unknown irritative gas (1), hydrochloric acid and sodium cyanide mix (1), unknown white powder (1), antiseptic dye (1), and chlorine gas and white phosphorous mix (1).

Conclusion:

The use of chemical weapons in warfare, though prohibited by the Chemical Weapons Convention (CWC), remains a rare but concerning terrorist attack methodology. In recent years, there have been more instances where potentially deadly chemicals have been used in civilian settings. Dual use industrial chemicals, in particular, pose a significant concern. Acid was the most commonly used chemical weapon in 52 attacks. Tear gas, chlorine, and cyanide were each used in over 20 attacks. Both DM and CTM specialists advocate for better preparedness and response training for intentional events in civilian settings.
HUME’S PRINCIPLE, BAD COMPANY, AND THE AXIOM OF CHOICE
Authors: ROBERTS SAM , SHAPIRO STEWART
Published: April 2022

One prominent criticism of the abstractionist program is the so-called Bad Company objection. The complaint is that abstraction principles cannot in general be a legitimate way to introduce mathematical theories, since some of them are inconsistent. The most notorious example, of course, is Frege’s Basic Law V. A common response to the objection suggests that an abstraction principle can be used to legitimately introduce a mathematical theory precisely when it is stable: when it can be made true on all sufficiently large domains. In this paper, we raise a worry for this response to the Bad Company objection. We argue, perhaps surprisingly, that it requires very strong assumptions about the range of the second-order quantifiers; assumptions that the abstractionist should reject.
Ionospheric Reconstruction Using GNSS Signals Around an Anomaly Crest Location in Indian Longitude Sector
Authors: Goswami Samiddha , Chaudhuri Antara , Paul Ashik
Published: April 2022

The present study aims to reconstruct the vertical ionospheric electron density (IED) profile using computerized ionospheric tomography (CIT) techniques, over the northern crest of the equatorial ionization anomaly (EIA) which is one of the most geo‐physically sensitive regions of Indian longitude sector. Total electron content (TEC) measurements obtained from GNSS signals from receivers located at Kolkata (22.57°N, 88.36°E), Purulia (23.33°N, 86.36°E), and Siliguri (26.73°N, 88.39°E) and International GNSS Service (IGS) stations of Port Blair (11.64°N, 92.71°E), Bangalore (13.02°N, 77.57°E), Hyderabad (17.42°N, 78.55°E), Lucknow (26.91°N, 80.96°E) and Lhasa (29.66°N, 91.10°E) have been incorporated into the tomography algorithm for ionospheric reconstructions. Among the different iterative techniques used for retrieving IED profiles on a 2‐dimensional altitude versus latitude plane fixed at a certain longitude, simultaneous iterative reconstruction technique (SIRT) was shown to be the optimum choice based on the representation of the EIA phenomenon and reconstruction accuracy. A comparative assessment between two ionospheric models IRI2016 and PIM1.4 was performed, with PIM based initial guess for inversions resulting in lower reconstruction errors. The 2D CIT algorithm was then used to reconstruct the hourly vertical IED profiles to study the impact of the severe G4‐class St. Patrick's Day storm on 17 March 2015 and reconstructed electron densities showed a large increase over the values obtained from the geomagnetically quiet day of 10 March 2015, indicating a positive ionospheric storm phase. Ionospheric response to the G1‐class geomagnetic disturbance on 5 December 2017 and the average F‐region IED values have also been compared with a geomagnetically quiet day of 3 December 2017.
Improved Prediction of Hydraulic Conductivity With a Soil Water Retention Curve That Accounts for Both Capillary and Adsorption Forces
Authors: Wang Yunquan , Ma Rui , Zhu Gaofeng
Published: April 2022

Hydraulic conductivity curves (HCCs) are important inputs in land surface modeling. The general way for predicting an HCC from a soil water retention curve (SWRC) requires an additional input of the saturated hydraulic conductivity. However, the macro effect near saturation often results in difficulty and poor performance when predicting the conductivity. In this paper, we introduce a novel method for predicting the HCC fully from the SWRC, requiring no additional parameters. This is achieved by applying an estimated conductivity (from the SWRC) in the dry range as a new matching point, in addition to modifying an existing HCC model that accounts for both capillary and adsorption forces. Testing with a total of 159 soil samples indicated that the new model substantially improves the prediction of the HCC in compared with the model with the input of the saturated hydraulic conductivity, with the R2 increased from 0.48 to 0.76 and the root‐mean‐square error value reduced from 1.60 to 0.81 cm d−1. The abrupt drop near saturation of the HCC model for soils with small n values close to 1.0, which is a parameter used in shaping the SWRC, was also overcome by forcing the water content be saturated above a fixed potential of −1 cm.
A Novel Approach to Analyze the Isolation Valve System Based on the Complex Network Theory
Authors: Giustolisi Orazio , Ciliberti Francesco Gino , Berardi Luigi , Laucelli Daniele Biagio
Published: April 2022

Complex Network Theory (CNT) studies network models and centrality metrics to deal with reliability/vulnerability assessment in networked systems. Classic CNT analyses evaluate the impact of failure of single vertices/edge elements on system connectivity assuming that all vertices/nodes have the same relevance. In Water Distribution Networks (WDNs), the Isolation Valve System (IVS) plays a crucial role for system reliability because a pipe failure asks for valves shutdown to isolate that pipe, usually requiring the isolation of a larger network segment, having its intrinsic relevance. This circumstance makes classic connectivity analyses and metrics of CNT misleading in reliability assessment of WDN. This work proposes a novel approach to analyze IVS, which is based on the construction of the graph of segments and isolation valves generated by the IVS. The application of the recently proposed relevance‐based (WDN‐tailored) betweenness centrality to such graph is used to rank the importance of segments and isolation valves. Two WDNs of different sizes are used to demonstrate and discuss the strategy also from a practical perspective.
Effectiveness of a 3-year community-based intervention for blood pressure reduction among adults: a repeated cross-sectional study with a comparison area
Authors: Ghammam Rim , Maatoug Jihene , Harrabi Imed , Ben Fredj Sihem , Zammit Nawel , Laatikainen Tiina , Vartiainen Erkki , Neupane Dinesh , Ghannem Hassen
Published: April 2022

Raised blood pressure is the leading risk factor for cardiovascular diseases. We aimed to demonstrate the effectiveness of a 3-year community-based healthy lifestyle promotion intervention at a neighbourhood level for blood pressure reduction among adults in the context of a political transition. We conducted repeated cross-sectional surveys including 1880 (940 from each area) participants at baseline and 1977 (1001 in the intervention area; 976 comparison area) participants at follow-up. Data collection was conducted through home visits. Multiple linear regression models were used to identify the intervention effect and factors associated with blood pressure change in each area. The prevalence of hypertension was 4.4% lower (35.8% vs. 31.4%) in the intervention area after 3 years (p = 0.044). The mean systolic and diastolic blood pressures changed significantly in the intervention area, from 132.4 ± 19.2 mmHg at baseline to 130.6 ± 17.7 mmHg at follow-up (p = 0.035) and from 78.7 ± 11.8 mmHg to 76.9 ± 11.1 mmHg (p < 10−3), respectively. In the control group, the mean systolic blood pressure increased from 129.4 ± 17.8 mmHg to 130.4 ± 17.9 mmHg (p = 0.38). A significant protective effect of the intervention on systolic (β = −0.4; 95% CI: −0.76; −0.06) and diastolic blood pressures (β = −0.22; 95% CI: −0.38; −0.07) was found in the intervention area. In the control area, the effect was not significant for systolic blood pressure. Lifestyle intervention at the neighbourhood level, in the context of a sociopolitical transition, was found to be effective for reducing blood pressure in Sousse, Tunisia. This approach could be scaled up and applied in other similar settings. Future research also needs to focus on designing, implementing, and evaluating multisectoral action plans and legislative measures.
Real-time molecular imaging of near-surface tissue using Raman spectroscopy
Authors: Yang Wei , Knorr Florian , Latka Ines , Vogt Matthias , Hofmann Gunther O. , Popp Jürgen , Schie Iwan W.
Published: April 2022

The steady progress in medical diagnosis and treatment of diseases largely hinges on the steady development and improvement of modern imaging modalities. Raman spectroscopy has attracted increasing attention for clinical applications as it is label-free, non-invasive, and delivers molecular fingerprinting information of a sample. In combination with fiber optic probes, it also allows easy access to different body parts of a patient. However, image acquisition with fiber optic probes is currently not possible. Here, we introduce a fiber optic probe-based Raman imaging system for the real-time molecular virtual reality data visualization of chemical boundaries on a computer screen and the physical world. The approach is developed around a computer vision-based positional tracking system in conjunction with photometric stereo and augmented and mixed chemical reality, enabling molecular imaging and direct visualization of molecular boundaries of three-dimensional surfaces. The proposed approach achieves a spatial resolution of 0.5 mm in the transverse plane and a topology resolution of 0.6 mm, with a spectral sampling frequency of 10 Hz, and can be used to image large tissue areas in a few minutes, making it highly suitable for clinical tissue-boundary demarcation. A variety of applications on biological samples, i.e., distribution of pharmaceutical compounds, brain-tumor phantom, and various types of sarcoma have been characterized, showing that the system enables rapid and intuitive assessment of molecular boundaries.
Early life oxytocin treatment improves thermo-sensory reactivity and maternal behavior in neonates lacking the autism-associated gene Magel2
Authors: Da Prato Laura Caccialupi , Zayan Ugo , Abdallah Dina , Point Vanessa , Schaller Fabienne , Pallesi-Pocachard Emilie , Montheil Aurélie , Canaan Stéphane , Gaiarsa Jean-Luc , Muscatelli Françoise , Matarazzo Valéry
Published: April 2022

Atypical responses to sensory stimuli are considered as a core aspect and early life marker of autism spectrum disorders (ASD). Although recent findings performed in mouse ASD genetic models report sensory deficits, these were explored exclusively during juvenile or adult period. Whether sensory dysfunctions might be present at the early life stage and rescued by therapeutic strategy are fairly uninvestigated. Here we found that under cool environment neonatal mice lacking the autism-associated gene Magel2 present pup calls hypo-reactivity and are retrieved with delay by their wild-type dam. This neonatal atypical sensory reactivity to cool stimuli was not associated with autonomic thermoregulatory alteration but with a deficit of the oxytocinergic system. Indeed, we show in control neonates that pharmacogenetic inactivation of hypothalamic oxytocin neurons mimicked atypical thermosensory reactivity found in Magel2 mutants. Furthermore, pharmacological intranasal administration of oxytocin to Magel2 neonates was able to rescue both the atypical thermosensory response and the maternal pup retrieval. This preclinical study establishes for the first-time early life impairments in thermosensory integration and suggest a therapeutic potential benefit of intranasal oxytocin treatment on neonatal atypical sensory reactivity for autism.
Gut microbiota severely hampers the efficacy of NAD-lowering therapy in leukemia
Authors: ElMokh Oussama , Matsumoto Saki , Biniecka Paulina , Bellotti Axel , Schaeuble Karin , Piacente Francesco , Gallart-Ayala Hector , Ivanisevic Julijana , Stamenkovic Ivan , Nencioni Alessio , Nahimana Aimable , Duchosal Michel A.
Published: April 2022

Most cancer cells have high need for nicotinamide adenine dinucleotide (NAD+) to sustain their survival. This led to the development of inhibitors of nicotinamide (NAM) phosphoribosyltransferase (NAMPT), the rate-limiting NAD+ biosynthesis enzyme from NAM. Such inhibitors kill cancer cells in preclinical studies but failed in clinical ones. To identify parameters that could negatively affect the therapeutic efficacy of NAMPT inhibitors and propose therapeutic strategies to circumvent such failure, we performed metabolomics analyses in tumor environment and explored the effect of the interaction between microbiota and cancer cells. Here we show that tumor environment enriched in vitamin B3 (NAM) or nicotinic acid (NA) significantly lowers the anti-tumor efficacy of APO866, a prototypic NAMPT inhibitor. Additionally, bacteria (from the gut, or in the medium) can convert NAM into NA and thus fuel an alternative NAD synthesis pathway through NA. This leads to the rescue from NAD depletion, prevents reactive oxygen species production, preserves mitochondrial integrity, blunts ATP depletion, and protects cancer cells from death.

Our data in an in vivo preclinical model reveal that antibiotic therapy down-modulating gut microbiota can restore the anti-cancer efficacy of APO866. Alternatively, NAphosphoribosyltransferase inhibition may restore anti-cancer activity of NAMPT inhibitors in the presence of gut microbiota and of NAM in the diet.
circ_0004140 promotes LUAD tumor progression and immune resistance through circ_0004140/miR-1184/CCL22 axis
Authors: Liu Yanyan , Zhang Haodong , Zhang Wangli , Xiang Lanxin , Yin Zhucheng , Xu Hongli , Lu Ping , Ma Yifei , Xiong Lingyi , Zhang Xiangchen , Liang Xin , Luo Jing , Liang Xinjun
Published: April 2022

Lung adenocarcinoma (LUAD) is a highly prevalent cancer with high mortality. Immune resistance and tumor metastasis are the pivotal factors for the promotion of LUAD. CircRNAs have been revealed a crucial pre-clinical diagnostic and therapeutic potentials in LUAD. Herein, we identify a novel circRNA (circ_0004140), derived from the oncogene YAP1, which is up-regulated in LUAD. The high expression of circ_0004140 is correlated with poor prognosis and CTL cells dysfunction in LUAD patients. Knockdown of circ_0004140 regulated LUAD cells proliferation, migration, and apoptosis. Mechanistically, circ_0004140 served as a sponge of miR-1184 targeting C-C motif chemokine ligand 22(CCL22). Overexpression of CCL22 reversed the inhibitory effect induced by si-circ_0004140 on cells proliferation and migration. Moreover, we also revealed that elevated circ_ooo4140 was related to cytotoxic lymphocyte exhaustion, and a combination therapy of C-021 (CCL22/CCR4 axis inhibitor) and anti-PD-1 attenuated LUAD promotion and immune resistance. In conclusion, circ_0004140 may drive resistance to anti-PD-1 immunotherapy, providing a novel potential therapeutic target for LUAD treatment.
The Peter Watson Memorial Lecture “Vision for the World”
Authors: Taylor Hugh R.
Published: April 2022

In the 1990s attention was drawn to the huge global problem of blindness and vision loss; most of which was unnecessary, being preventable or treatable. This led to the global initiative, Vision 2020. Over the last 30 years a lot of progress has been made in developing and implementing eye care programmes to address this and particularly to reach underserved populations. In 2019 the World Health Organisation produced the World Report on Vision that sets a clear pathway to develop Integrated Person-centred Eye Care. Indicators have been developed to track progress and national governments are to report on their progress. Data on eye health and vision loss have been collected from multiple population-based studies and analysed by the Vision Loss Expert Group. These data show that although the prevalence rates of vision loss and blindness are decreasing around the world, the actual number of people affected is slowly increasing. This is due to both population growth and the aging of the population. To provide the equity in eye care that is required, attention needs to be paid to integrating eye care into primary care and linking it with other specialist services. An important step is the training and development of coordinated eye care teams that are resourced to meet their population-based needs and to monitor the progress being made.
Congruent evolutionary responses of European steppe biota to late Quaternary climate change
Authors: Kirschner Philipp , Perez Manolo F. , Záveská Eliška , Sanmartín Isabel , Marquer Laurent , Schlick-Steiner Birgit C. , Alvarez Nadir ,   the STEPPE Consortium, Arthofer Wolfgang , Frajman Božo , Gamisch Alexander , Hilpold Andreas , Paun Ovidiu , Trucchi Emiliano , Záveská Eliška , Steiner Florian M. , Schönswetter Peter
Published: April 2022

Quaternary climatic oscillations had a large impact on European biogeography. Alternation of cold and warm stages caused recurrent glaciations, massive vegetation shifts, and large-scale range alterations in many species. The Eurasian steppe biome and its grasslands are a noteworthy example; they underwent climate-driven, large-scale contractions during warm stages and expansions during cold stages. Here, we evaluate the impact of these range alterations on the late Quaternary demography of several phylogenetically distant plant and insect species, typical of the Eurasian steppes. We compare three explicit demographic hypotheses by applying an approach combining convolutional neural networks with approximate Bayesian computation. We identified congruent demographic responses of cold stage expansion and warm stage contraction across all species, but also species-specific effects. The demographic history of the Eurasian steppe biota reflects major paleoecological turning points in the late Quaternary and emphasizes the role of climate as a driving force underlying patterns of genetic variance on the biome level.
Electrocorticographic evidence of a common neurocognitive sequence for mentalizing about the self and others
Authors: Tan Kevin M. , Daitch Amy L. , Pinheiro-Chagas Pedro , Fox Kieran C. R. , Parvizi Josef , Lieberman Matthew D.
Published: April 2022

Neuroimaging studies of mentalizing (i.e., theory of mind) consistently implicate the default mode network (DMN). Nevertheless, the social cognitive functions of individual DMN regions remain unclear, perhaps due to limited spatiotemporal resolution in neuroimaging. Here we use electrocorticography (ECoG) to directly record neuronal population activity while 16 human participants judge the psychological traits of themselves and others. Self- and other-mentalizing recruit near-identical cortical sites in a common spatiotemporal sequence. Activations begin in the visual cortex, followed by temporoparietal DMN regions, then finally in medial prefrontal regions. Moreover, regions with later activations exhibit stronger functional specificity for mentalizing, stronger associations with behavioral responses, and stronger self/other differentiation. Specifically, other-mentalizing evokes slower and longer activations than self-mentalizing across successive DMN regions, implying lengthier processing at higher levels of representation. Our results suggest a common neurocognitive pathway for self- and other-mentalizing that follows a complex spatiotemporal gradient of functional specialization across DMN and beyond.
Projections of faster onset and slower decay of El Niño in the 21st century
Authors: Lopez Hosmay , Lee Sang-Ki , Kim Dongmin , Wittenberg Andrew T. , Yeh Sang-Wook
Published: April 2022

Future changes in the seasonal evolution of the El Niño—Southern Oscillation (ENSO) during its onset and decay phases have received little attention by the research community. This work investigates the projected changes in the spatio-temporal evolution of El Niño events in the 21st Century (21 C), using a multi-model ensemble of coupled general circulation models subjected to anthropogenic forcing. Here we show that El Niño is projected to (1) grow at a faster rate, (2) persist longer over the eastern and far eastern Pacific, and (3) have stronger and distinct remote impacts via teleconnections. These changes are attributable to significant changes in the tropical Pacific mean state, dominant ENSO feedback processes, and an increase in stochastic westerly wind burst forcing in the western equatorial Pacific, and may lead to more significant and persistent global impacts of El Niño in the future.
Mechanical control of innate immune responses against viral infection revealed in a human lung alveolus chip
Authors: Bai Haiqing , Si Longlong , Jiang Amanda , Belgur Chaitra , Zhai Yunhao , Plebani Roberto , Oh Crystal Yuri , Rodas Melissa , Patil Aditya , Nurani Atiq , Gilpin Sarah E. , Powers Rani K. , Goyal Girija , Prantil-Baun Rachelle , Ingber Donald E.
Published: April 2022

Mechanical breathing motions have a fundamental function in lung development and disease, but little is known about how they contribute to host innate immunity. Here we use a human lung alveolus chip that experiences cyclic breathing-like deformations to investigate whether physical forces influence innate immune responses to viral infection. Influenza H3N2 infection of mechanically active chips induces a cascade of host responses including increased lung permeability, apoptosis, cell regeneration, cytokines production, and recruitment of circulating immune cells. Comparison with static chips reveals that breathing motions suppress viral replication by activating protective innate immune responses in epithelial and endothelial cells, which are mediated in part through activation of the mechanosensitive ion channel TRPV4 and signaling via receptor for advanced glycation end products (RAGE). RAGE inhibitors suppress cytokines induction, while TRPV4 inhibition attenuates both inflammation and viral burden, in infected chips with breathing motions. Therefore, TRPV4 and RAGE may serve as new targets for therapeutic intervention in patients infected with influenza and other potential pandemic viruses that cause life-threatening lung inflammation.
Contrasting social and non-social sources of predictability in human mobility
Authors: Chen Zexun , Kelty Sean , Evsukoff Alexandre G. , Welles Brooke Foucault , Bagrow James , Menezes Ronaldo , Ghoshal Gourab
Published: April 2022

Social structures influence human behavior, including their movement patterns. Indeed, latent information about an individual’s movement can be present in the mobility patterns of both acquaintances and strangers. We develop a “colocation” network to distinguish the mobility patterns of an ego’s social ties from those not socially connected to the ego but who arrive at a location at a similar time as the ego. Using entropic measures, we analyze and bound the predictive information of an individual’s mobility pattern and its flow to both types of ties. While the former generically provide more information, replacing up to 94% of an ego’s predictability, significant information is also present in the aggregation of unknown colocators, that contain up to 85% of an ego’s predictive information. Such information flow raises privacy concerns: individuals sharing data via mobile applications may be providing actionable information on themselves as well as others whose data are absent.
Maternal and child social support and food availability in relation to child growth in four low- and middle-income countries
Authors: Lee Hwa-Young , Song In Han , Kawachi Ichiro
Published: April 2022

Previous studies showed positive associations between specific types of social capital and child nutritional status. Our study examined whether improved food availability mediates the impact of maternal and child social support on child nutritional status in four low- and middle-income countries. We used data from the Young Lives cohort study, comprising 1,000 children aged 8 and 12 in Vietnam and Ethiopia, 1008 in India, and 714 in Peru. The outcome variables were the z-scores for height for age and body mass index (HAZ and BAZ, respectively). The causal mediation analysis framework was used. In Peru, above-median values of maternal social support and receiving child financial support were positively associated with HAZ at age 12. The level of maternal financial support was positively associated with BAZ among 12-year-old children in India. Peru was the only country where a positive association was found between food availability and maternal financial support among children aged 12. However, food availability did not mediate the effect of maternal financial support on HAZ at age 12. Strengthening social support to improve child nutritional status, especially by improving food availability, may not be a sufficient intervention in resource-poor settings because sources of support may lack sufficient food resources to share. However, more comprehensive measurements of social support and food security are necessary to better understand the mechanism of social support and child nutritional status.
Hysteretic hERG channel gating current recorded at physiological temperature
Authors: Jones David K.
Published: April 2022

Cardiac hERG channels comprise at least two subunits, hERG 1a and hERG 1b, and drive cardiac action potential repolarization. hERG 1a subunits contain a cytoplasmic PAS domain that is absent in hERG 1b. The hERG 1a PAS domain regulates voltage sensor domain (VSD) movement, but hERG VSD behavior and its regulation by the hERG 1a PAS domain have not been studied at physiological temperatures. We recorded gating charge from homomeric hERG 1a and heteromeric hERG 1a/1b channels at near physiological temperatures (36 ± 1 °C) using pulse durations comparable in length to the human ventricular action potential. The voltage dependence of deactivation was hyperpolarized relative to activation, reflecting VSD relaxation at positive potentials. These data suggest that relaxation (hysteresis) works to delay pore closure during repolarization. Interestingly, hERG 1a VSD deactivation displayed a double Boltzmann distribution, but hERG 1a/1b deactivation displayed a single Boltzmann. Disabling the hERG 1a PAS domain using a PAS-targeting antibody similarly transformed hERG 1a deactivation from a double to a single Boltzmann, highlighting the contribution of the PAS in regulating VSD movement. These data represent, to our knowledge, the first recordings of hERG gating charge at physiological temperature and demonstrate that VSD relaxation (hysteresis) is present in hERG channels at physiological temperature.
A Saccharomyces eubayanus haploid resource for research studies
Authors: Molinet Jennifer , Urbina Kamila , Villegas Claudia , Abarca Valentina , Oporto Christian I. , Villarreal Pablo , Villarroel Carlos A. , Salinas Francisco , Nespolo Roberto F. , Cubillos Francisco A.
Published: April 2022

Since its identification,Saccharomyces eubayanushas been recognized as the missing parent of the lager hybrid,S. pastorianus. This wild yeast has never been isolated from fermentation environments, thus representing an interesting candidate for evolutionary, ecological and genetic studies. However, it is imperative to develop additional molecular genetics tools to ease manipulation and thus facilitate future studies. With this in mind, we generated a collection of stable haploid strains representative of three main lineages described inS. eubayanus(PB-1, PB-2 and PB-3), by deleting theHOgene using CRISPR-Cas9 and tetrad micromanipulation. Phenotypic characterization under different conditions demonstrated that the haploid derivates were extremely similar to their parental strains. Genomic analysis in three strains highlighted a likely low frequency of off-targets, and sequencing of a single tetrad evidenced no structural variants in any of the haploid spores. Finally, we demonstrate the utilization of the haploid set by challenging the strains under mass-mating conditions. In this way, we found thatS. eubayanusunder liquid conditions has a preference to remain in a haploid state, unlikeS. cerevisiaethat mates rapidly. This haploid resource is a novel set of strains for future yeast molecular genetics studies.
Impact of experience on visual behavior and driving performance of high-speed train drivers
Authors: Du Yang , Zhi Jin-yi , He Si-jun
Published: April 2022

This study investigated the impact of experience on the visual behavior and driving performance of high-speed train drivers, and explored the correlation between visual behavior and driving performance. Through a simulated driving task, eye movement data and operating data of novice drivers, trainee drivers, and experienced drivers in the traction stage, normal operation process stage, and braking stage were collected. Variance and linear regression were used to analyze the difference and correlation between indicators. The results show that experience could change the driver’s information collection method from long fixation to multi-frequency. Experience also increased the consistency of group operations and reduced the likelihood of hazard occurrences. Therefore, driving performance can be improved by reducing the average fixation duration of information through interface optimization.
Assessment of the mechanical suppression of nonuniform electrodeposition in lithium metal batteries
Authors: Chang Shuenn-Jyh , Chen Chih-Hung , Chen Kuo-Ching
Published: April 2022

The mechanical suppression capacity of semi-solid electrolytes is assessed using two efficient roughness analyses. Our results summarized in design maps provide the guidelines for the development of dendrite-suppressing semi-solid electrolytes.
New opportunities for ultrafast and highly enantio-sensitive imaging of chiral nuclear dynamics enabled by synthetic chiral light
Authors: Ayuso David
Published: April 2022

Synthetic chiral light enables ultrafast and highly efficient imaging and control of molecular chirality. Here we explore how this giant enantio-sensitivity could be exploited to monitor, in real time, chiral nuclear dynamics during chemical reactions.
Arbutus unedo leaf extracts as potential dairy preservatives: case study on quark cheese
Authors: Derbassi Nabila , C. Pedrosa Mariana , Heleno Sandrina , Fernandes Filipa , Dias Maria Inês , Calhelha Ricardo C. , Rodrigues Paula , Carocho Marcio , Ferreira Isabel C. F. R. , Barros Lillian
Published: April 2022

The plant kingdom is an endless source of molecules that can be applied in almost all realms of society.
Integrating smartphone-assisted ratiometric fluorescent sensors with in situ hydrogel extraction for visual detection of organophosphorus pesticides
Authors: Tong Xia , Cai Guihan , Zhu Yongfeng , Tong Chaoying , Wang Fang , Guo Ying , Shi Shuyun
Published: April 2022

Rapid, reliable and on-site detection of organophosphorus pesticides (OPs) on fruit or vegetable surfaces is necessary in real life.
Mechanochemical IMCR and IMCR-post transformation domino strategies: towards the sustainable DOS of dipeptide-like and heterocyclic peptidomimetics
Authors: Pharande Shrikant G. , Rentería-Gómez Manuel A. , Gámez-Montaño Rocío
Published: April 2022

A facile, rapid, sustainable one-pot Diversity Oriented Synthesis of peptidomimeticsviamechanochemical IMCR-based domino strategies.
Ultrasensitive multiwall carbon nanotube-mesoporous MCM-41 hybrid-based platform for the electrochemical detection of ascorbic acid
Authors: Vaschetti Virginia M. , Viada Benjamín N. , Tamborelli Alejandro , Eimer Griselda A. , Rivas Gustavo A. , Dalmasso Pablo R.
Published: April 2022

An ultrasensitive multiwall carbon nanotube-MCM-41 hybrid-based ascorbic acid sensor for electro-detection in real samples is proposed. The MWCNT–MCM-41 hybrid preparation via dispersion was optimized through an experimental design based on CCD/RSM.