bluuebunny/crossref_metadata_2025 huggingface dataset:
The radio continuum perspective on cosmic-ray transport in external galaxies
Authors: Heesen Volker
Published: December 2021

Radio continuum observations of external galaxies provide us with an excellent outside view on the distribution of cosmic-ray electrons in the disc and halo. In this review, we summarise the current state of what we have learned from modelling such observations with cosmic-ray transport, paying particular attention to the question to what extent we can exploit radio haloes when studying galactic winds. We have developed the user-friendly framework spinnaker to model radio haloes with either pure advection or diffusion, allowing us to study both diffusion coefficients and advection speeds in nearby galaxies. Using these models, we show that we can identify galaxies with winds using both morphology and radio spectral indices of radio haloes. Advective radio haloes are ubiquitous, indicating that already fairly low values of the star formation rate (SFR) surface density ($\Sigma_{ \mathrm{SFR}}$

Σ
SFR

) can trigger galactic winds. The advection speeds scale with SFR, $\Sigma_{\mathrm{SFR}}$

Σ
SFR

, and rotation speed as expected for stellar feedback-driven winds. Accelerating winds are in agreement with our radio spectral index data, but this is sensitive to the magnetic field parametrisation, so that constant wind speeds cannot be ruled out either. The question to what extent cosmic rays can be a driving force behind winds is still an open issue and we discuss only in passing how a simple iso-thermal wind model could fit our data. Nevertheless, the comparison with inferences from observations and theory looks promising with radio continuum offering a complementary view on galactic winds. We finish with a perspective on future observations and challenges lying ahead.
Attribution of typhoon-induced torrential precipitation in Central Vietnam, October 2020
Authors: Luu Linh N. , Scussolini Paolo , Kew Sarah , Philip Sjoukje , Hariadi Mugni Hadi , Vautard Robert , Van Mai Khiem , Van Vu Thang , Truong Kien Ba , Otto Friederike , van der Schrier Gerard , van Aalst Maarten K. , van Oldenborgh Geert Jan
Published: December 2021

In October 2020, Central Vietnam was struck by heavy rain resulting from a sequence of 5 tropical depressions and typhoons. The immense amount of water led to extensive flooding and landslides that killed more than 200 people, injured more than 500 people, and caused direct damages valued at approximately 1.2 billion USD. Here, we quantify how the intensity of the precipitation leading to such exceptional impacts is attributable to anthropogenic climate change. First, we define the event as the regional maximum of annual maximum 15-day average rainfall (Rx15day). We then analyse the trend in Rx15day over Central Vietnam from the observations and simulations in the PRIMAVERA and CORDEX-CORE ensembles, which pass our evaluation tests, by applying the generalised extreme value (GEV) distribution in which location and scale parameters exponentially covary with increasing global temperatures. Combining these observations and model results, we find that the 2020 event, occurring about once every 80 years (at least 17 years), has not changed in either probability of occurrence (a factor 1.0, ranging from 0.4 to 2.4) or intensity (0%, ranging from −8 to +8%) in the present climate in comparison with early-industrial climate. This implies that the effect of human-induced climate change contributing to this persistent extreme rainfall event is small compared to natural variability. However, given the scale of damage of this hazard, our results underline that more investment in disaster risk reduction for this type of rainfall-induced flood hazard is of importance, even independent of the effect of anthropogenic climate change. Moreover, as both observations and model simulations will be extended with the passage of time, we encourage more climate change impact investigations on the extreme in the future that help adaptation and mitigation plans and raise awareness in the country.
Maintaining AUC and H-measure over time
Authors: Tatti Nikolaj
Published: December 2021

Measuring the performance of a classifier is a vital task in machine learning. The running time of an algorithm that computes the measure plays a very small role in an offline setting, for example, when the classifier is being developed by a researcher. However, the running time becomes more crucial if our goal is to monitor the performance of a classifier over time. In this paper we study three algorithms for maintaining two measures. The first algorithm maintains area under the ROC curve (AUC) under addition and deletion of data points in $$\mathcal {O} \mathopen {}\left( \log n\right)$$

O

log
n

time. This is done by maintaining the data points sorted in a self-balanced search tree. In addition, we augment the search tree that allows us to query the ROC coordinates of a data point in $$\mathcal {O} \mathopen {}\left( \log n\right)$$

O

log
n

time. In doing so we are able to maintain AUC in $$\mathcal {O} \mathopen {}\left( \log n\right)$$

O

log
n

time. Our next two algorithms involve in maintaining H-measure, an alternative measure based on the ROC curve. Computing the measure is a two-step process: first we need to compute a convex hull of the ROC curve, followed by a sum over the convex hull. We demonstrate that we can maintain the convex hull using a minor modification of the classic convex hull maintenance algorithm. We then show that under certain conditions, we can compute the H-measure exactly in $$\mathcal {O} \mathopen {}\left( \log ^2 n\right)$$

O

log
2

n

time, and if the conditions are not met, then we can estimate the H-measure in $$\mathcal {O} \mathopen {}\left( (\log n + \epsilon ^{-1})\log n\right)$$

O

(
log
n
+

ϵ

-
1

)
log
n

time. We show empirically that our methods are significantly faster than the baselines.
Batalin–Vilkovisky quantization of fuzzy field theories
Authors: Nguyen Hans , Schenkel Alexander , Szabo Richard J.
Published: December 2021

We apply the modern Batalin–Vilkovisky quantization techniques of Costello and Gwilliam to noncommutative field theories in the finite-dimensional case of fuzzy spaces. We further develop a generalization of this framework to theories that are equivariant under a triangular Hopf algebra symmetry, which in particular leads to quantizations of finite-dimensional analogues of the field theories proposed recently through the notion of ‘braided$$L_\infty $$L∞-algebras’. The techniques are illustrated by computing perturbative correlation functions for scalar and Chern–Simons theories on the fuzzy 2-sphere, as well as for braided scalar field theories on the fuzzy 2-torus.
Complement system component dysregulation is a distinctive feature of COVID-19 disease: a prospective and comparative analysis of patients admitted to the emergency department for suspected COVID-19 disease
Authors: Gauchel Nadine , Rieder Marina , Krauel Krystin , Goller Isabella , Jeserich Maren , Salzer Ulrich , Venhoff Ana Cecilia , Baldus Niklas , Pollmeier Luisa , Wirth Luisa , Kern Winfried , Rieg Siegbert , Busch Hans-Jörg , Hofmann Maike , Bode Christoph , Duerschmied Daniel , Lother Achim , Heger Lukas A.
Published: December 2021

The complement system (CS) plays a pivotal role in Coronavirus disease 2019 (COVID-19) pathophysiology. The objective of this study was to provide a comparative, prospective data analysis of CS components in an all-comers cohort and COVID-19 patients. Patients with suspected COVID-19 infection admitted to the Emergency department were grouped for definite diagnosis of COVID-19 and no COVID-19 accordingly. Clinical presentation, routine laboratory and von Willebrand factor (vWF) antigen as well as CS components 3, 4 and activated 5 (C5a) were assessed. Also, total complement activity via the classical pathway (CH50) was determined. Levels of calprotectin in serum were measured using an automated quantitative lateral flow assay. We included 80 patients in this prospective trial. Of those 19 (23.7%) were tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Patients with COVID-19 had higher levels of CS components 5a and 4 (54.79 [24.14–88.79] ng/ml vs. 35 [23.15–46.1] ng/ml; p = 0.0433 and 0.3772 [± 0.1056] g/L vs. 0.286 [0.2375–0.3748] g/L; p = 0.0168). COVID-19 patients had significantly higher levels of vWF antigen when compared to the control group (288.3 [± 80.26] % vs. 212 [151–320] %; p = 0.0469). There was a significant correlation between CS C3 and 5a with vWF antigen (rs = 0.5957 [p = 0.0131] and rs = 0.5015 [p = 0.042]) in COVID-19 patients. There was no difference in calprotectin plasma levels (4.786 [± 2.397] µg/ml vs. 4.233 [± 2.142] µg/ml; p = 0.4175) between both groups. This prospective data from a single centre all-comers cohort accentuates altered levels of CS components as a distinct feature of COVID-19 disease. Deregulation of CS component 3 and C5a are associated with increased vWF antigen possibly linking vascular damage to alternative CS activation in COVID-19.
Dimensions of ‘self-affine sponges’ invariant under the action of multiplicative integers
Authors: BRUNET GUILHEM
Published: December 2021

Let
$m_1 \geq m_2 \geq 2$
be integers. We consider subsets of the product symbolic sequence space
$(\{0,\ldots ,m_1-1\} \times \{0,\ldots ,m_2-1\})^{\mathbb {N}^*}$
that are invariant under the action of the semigroup of multiplicative integers. These sets are defined following Kenyon, Peres, and Solomyak and using a fixed integer
$q \geq 2$
. We compute the Hausdorff and Minkowski dimensions of the projection of these sets onto an affine grid of the unit square. The proof of our Hausdorff dimension formula proceeds via a variational principle over some class of Borel probability measures on the studied sets. This extends well-known results on self-affine Sierpiński carpets. However, the combinatoric arguments we use in our proofs are more elaborate than in the self-similar case and involve a new parameter, namely
$j = \lfloor \log _q ( {\log (m_1)}/{\log (m_2)} ) \rfloor $
. We then generalize our results to the same subsets defined in dimension
$d \geq 2$
. There, the situation is even more delicate and our formulas involve a collection of
$2d-3$
parameters.
Restaurant Wines: Bottle Margins and the By-the-Glass Option
Authors: Dearden James A. , Guo Xiaohui , Meyerhoefer Chad D.
Published: December 2021

Using a sample of New York City restaurants, we examine the relationship between a wine's bottle margin and whether the restaurant offers that same wine by the glass. We find that restaurants offer less expensive wines by the glass but set higher margins on these bottles than for similar wines offered only in bottles. Overall, offering wine by the glass is associated with a 5.0% increase in the bottle price and a 12.2% increase in the bottle margin. We find similar results for retail and wholesale markups of wine bottles. Our results offer evidence that settles a theoretical ambiguity in the menu-pricing literature (Anderson and Dana, 2009) about whether to raise or lower the price of a high-quantity package when introducing a low-quantity package of a good, as it applies to restaurant wine pricing. (JEL Classifications: L11, L83)
A longitudinal study examining the associations between interpersonal trauma and romantic relationships among college students
Authors: Smith Rebecca L. , Dick Danielle M. , Amstadter Ananda , Thomas Nathaniel ,   Spit for Science Working Group, Salvatore Jessica E.
Published: December 2021

We examined the associations between the developmental timing of interpersonal trauma exposure (IPT) and three indicators of involvement in and quality of romantic relationships in emerging adulthood: relationship status, relationship satisfaction, and partner alcohol use. We further examined whether these associations varied in a sex-specific manner. In a sample of emerging adult college students (N = 12,358; 61.5% female) assessed longitudinally across the college years, we found precollege IPT increased the likelihood of being in a relationship, while college-onset IPT decreased the likelihood. Precollege and college-onset IPT predicted lower relationship satisfaction, and college-onset IPT predicted higher partner alcohol use. There was no evidence that associations between IPT and relationship characteristics varied in a sex-specific manner. Findings indicate that IPT exposure, and the developmental timing of IPT, may affect college students’ relationship status. Findings also suggest that IPT affects their ability to form satisfying relationships with prosocial partners.
BEFORE THE MAYA: A REVIEW OF PALEOINDIAN AND ARCHAIC HUMAN SKELETONS FOUND IN THE MAYA REGION
Authors: Wrobel Gabriel D. , Hoggarth Julie A. , Marshall Aubree
Published: December 2021

This article presents a review of the earliest known skeletal remains in the Maya area, which are found in submerged caves in Mexico and rock shelters in Belize and date to the Paleoindian and Archaic periods. While few in number, several of these individuals have been the focus of intensive analyses, providing an emerging picture of life in the region before the transition to agriculture and settled village communities.
LOWLAND MAYA GENESIS: THE LATE ARCHAIC TO LATE EARLY FORMATIVE TRANSITION IN THE UPPER BELIZE RIVER VALLEY
Authors: Awe Jaime J. , Ebert Claire E. , Stemp W. James , Brown M. Kathryn , Sullivan Lauren A. , Garber James F.
Published: December 2021

The transition from the Late Archaic to the Late Early Formative period witnessed profound changes in the Maya lowlands. In addition to the establishment of the first settlements and agrarian communities, this critical phase of cultural development heralded the introduction of ceramics, saw changes in lithic technology, gave rise to inter-regional trade and exchange, and witnessed the introduction of a complex symbolic system expressed on portable objects. In this article, we synthesize data collected over the past several decades by various archaeological projects in western Belize to provide an overview of the cultural changes that unfolded during the Late Archaic to Late Early Formative period in the Upper Belize River Valley. We also provide evidence indicating that it was during this critical transitional period that we begin to see the establishment of several cultural traditions that became uniquely lowland Maya.
LIFE AND DEATH AMONG THE EARLIEST MAYA: A REVIEW OF EARLY AND MIDDLE PRECLASSIC BURIALS FROM THE MAYA WORLD
Authors: Wrobel Gabriel D. , López Pérez Raúl Alejandro , Ebert Claire E.
Published: December 2021

This article presents a review of the earliest Maya skeletal remains thus far found, including a list of 398 burials dating to the Early (1800–900 b.c.) and Middle Preclassic periods (900–300 b.c.) and adjacent regions. These sites are spread throughout the Maya region and the data allow basic descriptive syntheses about early mortuary behavior and aspects of health and diet. Poor preservation and differences in scoring and reporting severely limit the scope of interpretation possible at this point, but it is hoped that this review stimulates coordinated research into the biology of early groups.
Shallow‐Water Tsunami Deposits: Evidence From Sediment Cores and Numerical Wave Propagation of the 1601 CE Lake Lucerne Event
Authors: Nigg Valentin , Bacigaluppi Paola , Vetsch David F. , Vogel Hendrik , Kremer Katrina , Anselmetti Flavio S.
Published: December 2021

The 1601 CE earthquake (Mw ca. 5.9) in “Unterwalden,” Central Switzerland, triggered multiple subaqueous mass movements and a subaerial rockfall that generated tsunami waves with run‐up heights of up to 4 m and several hundred meters of inundation along the coastal lowlands of Lake Lucerne. In the shallow Lucerne Bay, historical chronicles reported an oscillation of the water with an initial amplitude of ∼1–2 m and a period of 10 min, which continued for several days after the event with decreasing amplitude. Here, we investigate the lake‐tsunami process chain from subaqueous mass movement‐generated tsunami to wave propagation and ultimately to sediment resuspension, transport, and deposition in the shallow‐water environment. The effects of the historical tsunami on Lucerne Bay are reconstructed using sediment‐core analysis and numerical simulation of wave propagation. A 60‐cm‐thick event deposit was recovered along a sediment‐core transect in the shallow waters and radiocarbon dated to 1306–1442 cal CE. The event deposit has a sharp basal contact with carbonate shell fragments followed upwards a normally graded succession of siliciclastic sand to silt with a high proportion of horizontally bedded wooden particles. The numerically simulated tsunami waves are characterized by a water‐surface displacement of up to 1.5 m and generate bed shear‐stresses that are likely capable of remobilizing large amounts of sediments in the Lucerne Bay area. Our study successfully links the sedimentology of event deposits with physical principles of sediment mobilization derived from numerical wave‐forward modeling, providing a tool to improve the identification and interpretation of potential tsunami deposits.
Using GRACE to Improve Altimetry's Ocean De‐Aliasing Model
Authors: Bonin J. A. , Save H.
Published: December 2021

We demonstrate that daily Gravity Recovery And Climate Experiment (GRACE) data can be used to improve the non‐tidal Dynamic Atmospheric Correction (DAC) used to de‐alias Jason altimetry and reduce high‐frequency errors. To accomplish this, we compute empirical orthogonal function (EOF) maps based on the ocean‐model part of the DAC, then fit the GRACE and Jason data to those maps. The resulting DAC and GRACE EOF time‐series are compared to the altimetry EOF time‐series, to determine which best represents the state of the ocean. We find that, for the first six modes in the North Pacific, 19 modes in the Southern Ocean, and three modes in the combined Indian/Atlantic/Equatorial‐Pacific region, GRACE is able to explain more of the 10–20‐day altimetry signal than the original de‐aliasing model can. We recombine these first GRACE modes with the remaining ocean‐only DAC data to produce an improved 10–20‐day model during times when GRACE data exists. We smoothly blend that series with the original model during times when there is no GRACE data, also restoring the faster frequencies from the original. The result is a blended model which explains 10%–30% more of altimetry's 10–20‐day variance in the Southern Ocean than the original DAC model did, 5%–10% more in the Atlantic and Indian Oceans, and is functionally equivalent in the Equatorial Pacific. The removal of the additional sub‐Nyquist‐frequency signals will result in better Jason altimetry data with fewer aliased signals incorrectly propagated to longer periods.
How Consistent Are Estimates of Roughness Parameters on a Rough Coral Reef?
Authors: Lindhart M. , Monismith S. G. , Khrizman A. , Mucciarone D. , Dunbar R.
Published: December 2021

Coral reefs are hydrodynamically rough, creating turbulent boundary layers that transport and mix various scalars that impact reef processes and also can be used to monitor reef health. Often reef boundary layer characteristics derived from a single instrument are assumed to accurately represent the study site. This approach relies on two assumptions: first, that the boundary layer is relatively homogeneous across the area of interest, and second, that two instruments displaced in space or with different spatiotemporal resolution would produce similar results when sampling the same flow. We deployed four velocimeters over a 15 × 20 m reef at 10 m depth in the Chagos Archipelago. The site had a 1 m tidal range, and waves were primarily locally generated wind waves with Hrms < 0.5 m. Depth‐averaged currents were typically 0.2 m/s. Friction velocities derived directly from Reynolds stress measurements by fitting the law of the wall show agreement between instruments (pairwise coefficients of determination R2 ranged from 0.53 to 0.86). Thus, the boundary layer appears to be spatially homogeneous, at least at the scale of our array, and it appears that in the present case friction velocities from one instrument are indeed generally representative of the site. We calculate drag coefficients using curve‐fitting and Structure‐from‐Motion photogrammetry, and while we find general agreement between estimates one instrument in particular produces drag coefficients an order of magnitude larger in comparison. Hence, some variability between instruments was observed, notably when high‐resolution instruments measured localized flow features.
Research progress on the tsRNA classification, function, and application in gynecological malignant tumors
Authors: Wen Jing-tao , Huang Zheng-hao , Li Qian-hui , Chen Xi , Qin Hong-lei , Zhao Yang
Published: December 2021

A large number of small non-coding RNAs derived from tRNAs, called tRNA-derived small RNA (tsRNAs), have been identified by high-throughput RNA sequencing of cell lines. Further research has revealed that they are not produced via random tRNA degradation, but through degradation by specific nuclease cleavages, such as Elac Ribonuclease Z 2 (ELAC2)/RNase Z, RNase L, Dicer, and angiogenin (ANG), the tsRNAs can be classified into the following types based on the location from which they have been derived from the parental tRNA: tRF-1s, tRF-3s, tRF-5s, tiRNA, and tRF-2s/i-tRFs. Moreover, tsRNAs are a type of small RNAs with diverse functions, including gene expression regulation, anti-apoptosis, translation inhibition, participation in epigenetic regulation, initial virus reverse transcription, promote virus replication and cell-to-cell communication. Certain types of tsRNAs are overexpressed in cancer tissues, but are underexpressed in normal tissues. Therefore, the relationship between tsRNAs and the occurrence and development of cancer has attracted significant research attention. Research advancements have contributed to further discoveries of the biological activities of tsRNAs, but the mechanisms of their biogenesis and functions have not been fully elucidated. This article reviews the classification and biological functions of tsRNAs, and introduces the research progress in gynecological malignancies.
SARS-CoV-2 uses metabotropic glutamate receptor subtype 2 as an internalization factor to infect cells
Authors: Wang Jinliang , Yang Guan , Wang Xinxin , Wen Zhiyuan , Shuai Lei , Luo Jie , Wang Chong , Sun Ziruo , Liu Renqiang , Ge Jinying , He Xijun , Hua Ronghong , Wang Xijun , Yang Xiao , Chen Weiye , Zhong Gongxun , Bu Zhigao
Published: December 2021

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uses angiotensin-converting enzyme 2 (ACE2) as a binding receptor to enter cells via clathrin-mediated endocytosis (CME). However, receptors involved in other steps of SARS-CoV-2 infection remain largely unknown. Here, we found that metabotropic glutamate receptor subtype 2 (mGluR2) is an internalization factor for SARS-CoV-2. Our results show that mGluR2 directly interacts with the SARS-CoV-2 spike protein and that knockdown of mGluR2 decreases internalization of SARS-CoV-2 but not cell binding. Further, mGluR2 is uncovered to cooperate with ACE2 to facilitate SARS-CoV-2 internalization through CME and mGluR2 knockout in mice abolished SARS-CoV-2 infection in the nasal turbinates and significantly reduced viral infection in the lungs. Notably, mGluR2 is also important for SARS-CoV spike protein- and Middle East respiratory syndrome coronavirus spike protein-mediated internalization. Thus, our study identifies a novel internalization factor used by SARS-CoV-2 and opens a new door for antiviral development against coronavirus infection.
Chemical heterogeneities reveal early rapid cooling of Apollo Troctolite 76535
Authors: Nelson William S. , Hammer Julia E. , Shea Thomas , Hellebrand Eric , Jeffrey Taylor G.
Published: December 2021

The evolution of the lunar interior is constrained by samples of the magnesian suite of rocks returned by the Apollo missions. Reconciling the paradoxical geochemical features of this suite constitutes a feasibility test of lunar differentiation models. Here we present the results of a microanalytical examination of the archetypal specimen, troctolite 76535, previously thought to have cooled slowly from a large magma body. We report a degree of intra-crystalline compositional heterogeneity (phosphorus in olivine and sodium in plagioclase) fundamentally inconsistent with prolonged residence at high temperature. Diffusion chronometry shows these heterogeneities could not have survived magmatic temperatures for >~20 My, i.e., far less than the previous estimated cooling duration of >100 My. Quantitative modeling provides a constraint on the thermal history of the lower lunar crust, and the textural evidence of dissolution and reprecipitation in olivine grains supports reactive melt infiltration as the mechanism by which the magnesian suite formed.
Deep neural network models reveal interplay of peripheral coding and stimulus statistics in pitch perception
Authors: Saddler Mark R. , Gonzalez Ray , McDermott Josh H.
Published: December 2021

Perception is thought to be shaped by the environments for which organisms are optimized. These influences are difficult to test in biological organisms but may be revealed by machine perceptual systems optimized under different conditions. We investigated environmental and physiological influences on pitch perception, whose properties are commonly linked to peripheral neural coding limits. We first trained artificial neural networks to estimate fundamental frequency from biologically faithful cochlear representations of natural sounds. The best-performing networks replicated many characteristics of human pitch judgments. To probe the origins of these characteristics, we then optimized networks given altered cochleae or sound statistics. Human-like behavior emerged only when cochleae had high temporal fidelity and when models were optimized for naturalistic sounds. The results suggest pitch perception is critically shaped by the constraints of natural environments in addition to those of the cochlea, illustrating the use of artificial neural networks to reveal underpinnings of behavior.
Southward expanding plate coupling due to variation in sediment subduction as a cause of Andean growth
Authors: Hu Jiashun , Liu Lijun , Gurnis Michael
Published: December 2021

Growth of the Andes has been attributed to Cenozoic subduction. Although climatic and tectonic processes have been proposed to be first-order mechanisms, their interaction and respective contributions remain largely unclear. Here, we apply three-dimensional, fully-dynamic subduction models to investigate the effect of trench-axial sediment transport and subduction on Andean growth, a mechanism that involves both climatic and tectonic processes. We find that the thickness of trench-fill sediments, a proxy of plate coupling (with less sediments causing stronger coupling), exerts an important influence on the pattern of crustal shortening along the Andes. The southward migrating Juan Fernandez Ridge acts as a barrier to the northward flowing trench sediments, thus expanding the zone of plate coupling southward through time. Consequently, the predicted history of Andean shortening is consistent with observations. Southward expanding crustal shortening matches the kinematic history of inferred compression. These results demonstrate the importance of climate-tectonic interaction on mountain building.
Ultralow dark current in near-infrared perovskite photodiodes by reducing charge injection and interfacial charge generation
Authors: Ollearo Riccardo , Wang Junke , Dyson Matthew J. , Weijtens Christ H. L. , Fattori Marco , van Gorkom Bas T. , van Breemen Albert J. J. M. , Meskers Stefan C. J. , Janssen René A. J. , Gelinck Gerwin H.
Published: December 2021

Metal halide perovskite photodiodes (PPDs) offer high responsivity and broad spectral sensitivity, making them attractive for low-cost visible and near-infrared sensing. A significant challenge in achieving high detectivity in PPDs is lowering the dark current density (JD) and noise current (in). This is commonly accomplished using charge-blocking layers to reduce charge injection. By analyzing the temperature dependence of JD for lead-tin based PPDs with different bandgaps and electron-blocking layers (EBL), we demonstrate that while EBLs eliminate electron injection, they facilitate undesired thermal charge generation at the EBL-perovskite interface. The interfacial energy offset between the EBL and the perovskite determines the magnitude and activation energy of JD. By increasing this offset we realized a PPD with ultralow JD and in of 5 × 10−8 mA cm−2 and 2 × 10−14 A Hz−1/2, respectively, and wavelength sensitivity up to 1050 nm, establishing a new design principle to maximize detectivity in perovskite photodiodes.
Depletion of central memory CD8+ T cells might impede the antitumor therapeutic effect of Mogamulizumab
Authors: Maeda Yuka , Wada Hisashi , Sugiyama Daisuke , Saito Takuro , Irie Takuma , Itahashi Kota , Minoura Kodai , Suzuki Susumu , Kojima Takashi , Kakimi Kazuhiro , Nakajima Jun , Funakoshi Takeru , Iida Shinsuke , Oka Mikio , Shimamura Teppei , Doi Toshihiko , Doki Yuichiro , Nakayama Eiichi , Ueda Ryuzo , Nishikawa Hiroyoshi
Published: December 2021

Regulatory T (Treg) cells are important negative regulators of immune homeostasis, but in cancers they tone down the anti-tumor immune response. They are distinguished by high expression levels of the chemokine receptor CCR4, hence their targeting by the anti-CCR4 monoclonal antibody mogamulizumab holds therapeutic promise. Here we show that despite a significant reduction in peripheral effector Treg cells, clinical responses are minimal in a cohort of patients with advanced CCR4-negative solid cancer in a phase Ib study (NCT01929486). Comprehensive immune-monitoring reveals that the abundance of CCR4-expressing central memory CD8+T cells that are known to play roles in the antitumor immune response is reduced. In long survivors, characterised by lower CCR4 expression in their central memory CD8+T cells possessed and/or NK cells with an exhausted phenotype, cell numbers are eventually maintained. Our study thus shows that mogamulizumab doses that are currently administered to patients in clinical studies may not differentiate between targeting effector Treg cells and central memory CD8+T cells, and dosage refinement might be necessary to avoid depletion of effector components during immune therapy.
A machine and human reader study on AI diagnosis model safety under attacks of adversarial images
Authors: Zhou Qianwei , Zuley Margarita , Guo Yuan , Yang Lu , Nair Bronwyn , Vargo Adrienne , Ghannam Suzanne , Arefan Dooman , Wu Shandong
Published: December 2021

While active efforts are advancing medical artificial intelligence (AI) model development and clinical translation, safety issues of the AI models emerge, but little research has been done. We perform a study to investigate the behaviors of an AI diagnosis model under adversarial images generated by Generative Adversarial Network (GAN) models and to evaluate the effects on human experts when visually identifying potential adversarial images. Our GAN model makes intentional modifications to the diagnosis-sensitive contents of mammogram images in deep learning-based computer-aided diagnosis (CAD) of breast cancer. In our experiments the adversarial samples fool the AI-CAD model to output a wrong diagnosis on 69.1% of the cases that are initially correctly classified by the AI-CAD model. Five breast imaging radiologists visually identify 29%-71% of the adversarial samples. Our study suggests an imperative need for continuing research on medical AI model’s safety issues and for developing potential defensive solutions against adversarial attacks.
A cryo-electron microscopy support film formed by 2D crystals of hydrophobin HFBI
Authors: Fan Hongcheng , Wang Bo , Zhang Yan , Zhu Yun , Song Bo , Xu Haijin , Zhai Yujia , Qiao Mingqiang , Sun Fei
Published: December 2021

Cryo-electron microscopy (cryo-EM) has become a powerful tool to resolve high-resolution structures of biomacromolecules in solution. However, air-water interface induced preferred orientations, dissociation or denaturation of biomacromolecules during cryo-vitrification remains a limiting factor for many specimens. To solve this bottleneck, we developed a cryo-EM support film using 2D crystals of hydrophobin HFBI. The hydrophilic side of the HFBI film adsorbs protein particles via electrostatic interactions and sequesters them from the air-water interface, allowing the formation of sufficiently thin ice for high-quality data collection. The particle orientation distribution can be regulated by adjusting the buffer pH. Using this support, we determined the cryo-EM structures of catalase (2.29 Å) and influenza haemagglutinin trimer (2.56 Å), which exhibited strong preferred orientations using a conventional cryo-vitrification protocol. We further show that the HFBI film is suitable to obtain high-resolution structures of small proteins, including aldolase (150 kDa, 3.28 Å) and haemoglobin (64 kDa, 3.6 Å). Our work suggests that HFBI films may have broad future applications in increasing the success rate and efficiency of cryo-EM.
Harnessing Twitter data to survey public attention and attitudes towards COVID-19 vaccines in the UK
Authors: Fazel Seena , Zhang Le , Javid Babak , Brikell Isabell , Chang Zheng
Published: December 2021

Attitudes to COVID-19 vaccination vary considerably within and between countries. Although the contribution of socio-demographic factors to these attitudes has been studied, the role of social media and how it interacts with news about vaccine development and efficacy is uncertain. We examined around 2 million tweets from 522,893 persons in the UK from November 2020 to January 2021 to evaluate links between Twitter content about vaccines and major scientific news announcements about vaccines. The proportion of tweets with negative vaccine content varied, with reductions of 20–24% on the same day as major news announcement. However, the proportion of negative tweets reverted back to an average of around 40% within a few days. Engagement rates were higher for negative tweets. Public health messaging could consider the dynamics of Twitter-related traffic and the potential contribution of more targeted social media campaigns to address vaccine hesitancy.
Proof of concept and development of a couple-based machine learning model to stratify infertile patients with idiopathic infertility
Authors: Bachelot Guillaume , Lévy Rachel , Bachelot Anne , Faure Céline , Czernichow Sébastien , Dupont Charlotte , Lamazière Antonin ,   Alifert Collaborative Group, Aknin Isabelle , Cedrin-Durnerin Isabelle , Cens Steven , di Clemente Nathalie , Guéant Jean-Louis , Hercberg Serge , Lalatonne Yoann , Racine Chrystèle , Sermondade Nathalie , Sutton Angela , Uthurriague Claude , Wolf Jean-Philippe , Favier Alain
Published: December 2021

We aimed to develop and evaluate a machine learning model that can stratify infertile/fertile couples on the basis of their bioclinical signature helping the management of couples with unexplained infertility. Fertile and infertile couples were recruited in the ALIFERT cross-sectional case–control multicentric study between September 2009 and December 2013 (NCT01093378). The study group consisted of 97 infertile couples presenting a primary idiopathic infertility (> 12 months) from 4 French infertility centers compared with 100 fertile couples (with a spontaneously conceived child (< 2 years of age) and with time to pregnancy < 12 months) recruited from the healthy population of the areas around the infertility centers. The study group is comprised of 2 independent sets: a development set (n = 136 from 3 centers) serving to train the model and a test set (n = 61 from 1 center) used to provide an unbiased validation of the model. Our results have shown that: (i) a couple-modeling approach was more discriminant than models in which men’s and women’s parameters are considered separately; (ii) the most discriminating variables were anthropometric, or related to the metabolic and oxidative status; (iii) a refined model capable to stratify fertile vs. infertile couples with accuracy 73.8% was proposed after the variables selection (from 80 to 13). These influential factors (anthropometric, antioxidative, and metabolic signatures) are all modifiable by the couple lifestyle. The model proposed takes place in the management of couples with idiopathic infertility, for whom the decision-making tools are scarce. Prospective interventional studies are now needed to validate the model clinical use.

Trial registration: NCT01093378 ALIFERT https://clinicaltrials.gov/ct2/show/NCT01093378?term=ALIFERT&rank=1. Registered: March 25, 2010.
Immunoreactivity of the SARS-CoV-2 entry proteins ACE-2 and TMPRSS-2 in murine models of hormonal manipulation, ageing, and cardiac injury
Authors: Bengs Susan , Rossi Alexia , Haberecker Martina , Mikail Nidaa , Meisel Alexander , Haider Achi , Grämer Muriel , Portmann Angela , Todorov Atanas , Schönenberger Christof , Gebhard Caroline E. , Kuster Gabriela M. , Regitz-Zagrosek Vera , Gebhard Catherine
Published: December 2021

Previous work indicates that SARS-CoV-2 virus entry proteins angiotensin-converting enzyme 2 (ACE-2) and the cell surface transmembrane protease serine 2 (TMPRSS-2) are regulated by sex hormones. However, clinical studies addressing this association have yielded conflicting results. We sought to analyze the impact of sex hormones, age, and cardiovascular disease on ACE-2 and TMPRSS-2 expression in different mouse models. ACE-2 and TMPRSS-2 expression was analyzed by immunostaining in a variety of tissues obtained from FVB/N mice undergoing either gonadectomy or sham-surgery and being subjected to ischemia–reperfusion injury or transverse aortic constriction surgery. In lung tissues sex did not have a significant impact on the expression of ACE-2 and TMPRSS-2. On the contrary, following myocardial injury, female sex was associated to a lower expression of ACE-2 at the level of the kidney tubules. In addition, after myocardial injury, a significant correlation between younger age and higher expression of both ACE-2 and TMPRSS-2 was observed for lung alveoli and bronchioli, kidney tubules, and liver sinusoids. Our experimental data indicate that gonadal hormones and biological sex do not alter ACE-2 and TMPRSS-2 expression in the respiratory tract in mice, independent of disease state. Thus, sex differences in ACE-2 and TMPRSS-2 protein expression observed in mice may not explain the higher disease burden of COVID-19 among men.
Pharmacokinetics and central accumulation of delta-9-tetrahydrocannabinol (THC) and its bioactive metabolites are influenced by route of administration and sex in rats
Authors: Baglot Samantha L. , Hume Catherine , Petrie Gavin N. , Aukema Robert J. , Lightfoot Savannah H. M. , Grace Laine M. , Zhou Ruokun , Parker Linda , Rho Jong M. , Borgland Stephanie L. , McLaughlin Ryan J. , Brechenmacher Laurent , Hill Matthew N.
Published: December 2021

Up to a third of North Americans report using cannabis in the prior month, most commonly through inhalation. Animal models that reflect human consumption are critical to study the impact of cannabis on brain and behaviour. Most animal studies to date utilize injection of delta-9-tetrahydrocannabinol (THC; primary psychoactive component of cannabis). THC injections produce markedly different physiological and behavioural effects than inhalation, likely due to distinctive pharmacokinetics. The current study directly examined if administration route (injection versus inhalation) alters metabolism and central accumulation of THC and metabolites over time. Adult male and female Sprague–Dawley rats received either an intraperitoneal injection or a 15-min session of inhaled exposure to THC. Blood and brains were collected at 15, 30, 60, 90 and 240-min post-exposure for analysis of THC and metabolites. Despite achieving comparable peak blood THC concentrations in both groups, our results indicate higher initial brain THC concentration following inhalation, whereas injection resulted in dramatically higher 11-OH-THC concentration, a potent THC metabolite, in blood and brain that increased over time. Our results provide evidence of different pharmacokinetic profiles following inhalation versus injection. Accordingly, administration route should be considered during data interpretation, and translational animal work should strongly consider using inhalation models.
Circadian and chemotherapy-related changes in urinary modified nucleosides excretion in patients with metastatic colorectal cancer
Authors: Dulong S. , Huang Q. , Innominato P. F. , Karaboue A. , Bouchahda M. , Pruvost A. , Théodoro F. , Agrofoglio L. A. , Adam R. , Finkenstädt B. , Lévi F.
Published: December 2021

Urinary levels of modified nucleosides reflect nucleic acids turnover and can serve as non-invasive biomarkers for monitoring tumour circadian dynamics, and treatment responses in patients with metastatic colorectal cancer. In 39 patients, median overnight urinary excretion of LC-HRMS determinations of pseudouridine, was ~ tenfold as large as those of 1-methylguanosine, 1-methyladenosine, or 4-acetylcytidine, and ~ 100-fold as large as those of adenosine and cytidine. An increase in any nucleoside excretion after chemotherapy anticipated plasma carcinoembryonic antigen progression 1–2 months later and was associated with poor survival. Ten fractionated urines were collected over 2-days in 29 patients. The median value of the rhythm-adjusted mean of urinary nucleoside excretion varied from 64.3 for pseudouridine down to 0.61 for cytidine. The rhythm amplitudes relative to the 24-h mean of 6 nucleoside excretions were associated with rest duration, supporting a tight link between nucleosides turnover and the rest-activity rhythm. Moreover, the amplitude of the 1-methylguanosine rhythm was correlated with the rest-activity dichotomy index, a significant predictor of survival outcome in prior studies. In conclusion, urinary excretion dynamics of modified nucleosides appeared useful for the characterization of the circadian control of cellular proliferation and for tracking early responses to treatments in colorectal cancer patients.
Training a deep learning model for single-cell segmentation without manual annotation
Authors: Din Nizam Ud , Yu Ji
Published: December 2021

Advances in the artificial neural network have made machine learning techniques increasingly more important in image analysis tasks. Recently, convolutional neural networks (CNN) have been applied to the problem of cell segmentation from microscopy images. However, previous methods used a supervised training paradigm in order to create an accurate segmentation model. This strategy requires a large amount of manually labeled cellular images, in which accurate segmentations at pixel level were produced by human operators. Generating training data is expensive and a major hindrance in the wider adoption of machine learning based methods for cell segmentation. Here we present an alternative strategy that trains CNNs without any human-labeled data. We show that our method is able to produce accurate segmentation models, and is applicable to both fluorescence and bright-field images, and requires little to no prior knowledge of the signal characteristics.
Subnetwork representation learning for discovering network biomarkers in predicting lymph node metastasis in early oral cancer
Authors: Kim Minsu , Lee Sangseon , Lim Sangsoo , Lee Doh Young , Kim Sun
Published: December 2021

Cervical lymph node metastasis is the leading cause of poor prognosis in oral tongue squamous cell carcinoma and also occurs in the early stages. The current clinical diagnosis depends on a physical examination that is not enough to determine whether micrometastasis remains. The transcriptome profiling technique has shown great potential for predicting micrometastasis by capturing the dynamic activation state of genes. However, there are several technical challenges in using transcriptome data to model patient conditions: (1) An Insufficient number of samples compared to the number of genes, (2) Complex dependence between genes that govern the cancer phenotype, and (3) Heterogeneity between patients between cohorts that differ geographically and racially. We developed a computational framework to learn the subnetwork representation of the transcriptome to discover network biomarkers and determine the potential of metastasis in early oral tongue squamous cell carcinoma. Our method achieved high accuracy in predicting the potential of metastasis in two geographically and racially different groups of patients. The robustness of the model and the reproducibility of the discovered network biomarkers show great potential as a tool to diagnose lymph node metastasis in early oral cancer.
Evaluation of anticancer activity in vitro of a stable copper(I) complex with phosphine-peptide conjugate
Authors: Komarnicka Urszula K. , Pucelik Barbara , Wojtala Daria , Lesiów Monika K. , Stochel Grażyna , Kyzioł Agnieszka
Published: December 2021

[CuI(2,9-dimethyl-1,10-phenanthroline)P(p-OCH3-Ph)2CH2SarcosineGlycine] (1-MPSG), highly stable in physiological media phosphino copper(I) complex—is proposed herein as a viable alternative to anticancer platinum-based drugs. It is noteworthy that, 1-MPSG significantly and selectively reduced cell viability in a 3D spheroidal model of human lung adenocarcinoma (A549), in comparison with non-cancerous HaCaT cells. Confocal microscopy and an ICP-MS analysis showed that 1-MPSG effectively accumulates inside A549 cells with colocalization in mitochondria and nuclei. A precise cytometric analysis revealed a predominance of apoptosis over the other types of cell death. In the case of HaCaT cells, the overall cytotoxicity was significantly lower, indicating the selective activity of 1-MPSG towards cancer cells. Apoptosis also manifested itself in a decrease in mitochondrial membrane potential along with the activation of caspases-3/9. Moreover, the caspase inhibitor (Z-VAD-FMK) pretreatment led to decreased level of apoptosis (more pronouncedly in A549 cells than in non-cancerous HaCaT cells) and further validated the caspases dependence in 1-MPSG-induced apoptosis. Furthermore, the 1-MPSG complex presumably induces the changes in the cell cycle leading to G2/M phase arrest in a dose-dependent manner. It was also observed that the 1-MPSG mediated intracellular ROS alterations in A549 and HaCaT cells. These results, proved by fluorescence spectroscopy, and flow cytometry, suggest that investigated Cu(I) compound may trigger apoptosis also through ROS generation.