bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Limited Hold on Equivalence Class Formation
Authors: Högnason Felix , Arntzen Erik
Published: July 2021

In an attempt to limit the opportunity to engage in mediating behavior, two groups of adult participants received preliminary training in identity matching with limited hold levels (LH) for responding of 0.7 s for the sample and 1.2 s for the comparisons. The two groups were subsequently trained to form three 5-member classes, using the same LH levels, where the A, B, D, and E stimuli were abstract stimuli, and the C stimuli were meaningful pictures. In two tests for emergent relations, the LH for Group Short was unchanged, whereas 5 s were added to the LH for the comparisons for Group Long. None of the participants in Group Short responded in accordance with stimulus equivalence in either of the two tests. In Group Long, one participant responded in accordance with stimulus equivalence in the first test, and an additional eight participants formed equivalence classes in the second test.
Memristor crossbar architectures for implementing deep neural networks
Authors: Liu Xiaoyang , Zeng Zhigang
Published: July 2021

The paper presents memristor crossbar architectures for implementing layers in deep neural networks, including the fully connected layer, the convolutional layer, and the pooling layer. The crossbars achieve positive and negative weight values and approximately realize various nonlinear activation functions. Then the layers constructed by the crossbars are adopted to build the memristor-based multi-layer neural network (MMNN) and the memristor-based convolutional neural network (MCNN). Two kinds of in-situ weight update schemes, which are the fixed-voltage update and the approximately linear update, respectively, are used to train the networks. Consider variations resulted from the inherent characteristics of memristors and the errors of programming voltages, the robustness of MMNN and MCNN to these variations is analyzed. The simulation results on standard datasets show that deep neural networks (DNNs) built by the memristor crossbars work satisfactorily in pattern recognition tasks and have certain robustness to memristor variations.
Hugoniot Data and Equation of State Parameters for an Ultra-High Performance Concrete
Authors: Sauer C. , Bagusat F. , Ruiz-Ripoll M.-L. , Roller C. , Sauer M. , Heine A. , Riedel W.
Published: July 2021

This work aims at the characterization of a modern concrete material. For this purpose, we perform two experimental series of inverse planar plate impact (PPI) tests with the ultra-high performance concrete B4Q, using two different witness plate materials. Hugoniot data in the range of particle velocities from 180 to 840 m/s and stresses from 1.1 to 7.5 GPa is derived from both series. Within the experimental accuracy, they can be seen as one consistent data set. Moreover, we conduct corresponding numerical simulations and find a reasonably good agreement between simulated and experimentally obtained curves. From the simulated curves, we derive numerical Hugoniot results that serve as a homogenized, mean shock response of B4Q and add further consistency to the data set. Additionally, the comparison of simulated and experimentally determined results allows us to identify experimental outliers. Furthermore, we perform a parameter study which shows that a significant influence of the applied pressure dependent strength model on the derived equation of state (EOS) parameters is unlikely. In order to compare the current results to our own partially reevaluated previous work and selected recent results from literature, we use simulations to numerically extrapolate the Hugoniot results. Considering their inhomogeneous nature, a consistent picture emerges for the shock response of the discussed concrete and high-strength mortar materials. Hugoniot results from this and earlier work are presented for further comparisons. In addition, a full parameter set for B4Q, including validated EOS parameters, is provided for the application in simulations of impact and blast scenarios.
Labor Participation and Gender Inequalities in India: Traditional Gender Norms in India and the Decline in the Labor Force Participation Rate (LFPR)
Authors: Costagliola Alessandra
Published: July 2021

Reduction in gender inequality has become a major component of development agendas, cited as a mechanism for improved access to health care, declining fertility rates, reduced poverty, and increased political and social participation of women. While women’s participation in the labor force is an essential component of increasing gender equity in the developing world, such participation can only be made possible under conditions that allow women to possess the level of autonomy and mobility necessary for engaging in the labor market. In this article, I explain that while women’s labor force participation is an essential component of gender equity, it is not the key to ensuring gender equality. To explain this, I examine India’s decline in women’s labor force participation rate (LFPR) despite its growing economy. I challenge arguments that rationalize that this decline is attributed to the U-shaped hypothesis, and I assert that this decline is associated with existing gendered notions of labor and persisting patriarchal and traditional values that discourage women from re-entering the labor force in the industrial and service sectors.
A thousand brains: toward biologically constrained AI
Authors: Hole Kjell Jørgen , Ahmad Subutai
Published: July 2021

This paper reviews the state of artificial intelligence (AI) and the quest to create general AI with human-like cognitive capabilities. Although existing AI methods have produced powerful applications that outperform humans in specific bounded domains, these techniques have fundamental limitations that hinder the creation of general intelligent systems. In parallel, over the last few decades, an explosion of experimental techniques in neuroscience has significantly increased our understanding of the human brain. This review argues that improvements in current AI using mathematical or logical techniques are unlikely to lead to general AI. Instead, the AI community should incorporate neuroscience discoveries about the neocortex, the human brain’s center of intelligence. The article explains the limitations of current AI techniques. It then focuses on the biologically constrainedThousand Brains Theorydescribing the neocortex’s computational principles. Future AI systems can incorporate these principles to overcome the stated limitations of current systems. Finally, the article concludes that AI researchers and neuroscientists should work together on specified topics to achieve biologically constrained AI with human-like capabilities.
Effect of permanent magnet material on failure-pressure of magnetic fluid seal
Authors: Zhang Tong , Li De-Cai , Li Yan-Wen
Published: July 2021

Material properties of permanent magnet in the magnetic fluid seal are important factors that determine the sealing effect. However, the relationship between the magnetic properties of permanent magnet and the failure-pressure has not been studied quantitatively in the available research. In this work, the relationship between material properties of permanent magnet and the failure-pressure of magnetic fluid seal was obtained from theoretical analysis and numerical simulation. The permanent magnet was changed in materials to calculate the failure-pressures of a typical magnetic fluid seal. The results show that the failure pressure of the magnetic fluid seal increases with the increase of the maximum magnetic energy product of the permanent magnet, but there is a turning point. After that, the failure-pressure decreases as the maximum magnetic energy product increases.
Effects of Testosterone Replacement Therapy on Glycolipid Metabolism Among Hypogonadal Men withT2DM: A Meta-Analysis And System Review Of Randomized Controlled Trials
Authors: Yu Xiaowei , Wei Zhentong , Liu Yanhong , Zhang XiaoYuan , Wang Qun
Published: July 2021

Introduction

Testosterone can improve glucose metabolism through multiple cellular mechanisms. However, it remains unclear as to whether hypogonadal men with type 2 diabetes mellitus (T2DM) can benefit from testosterone replacement therapy (TRT).

Aims

To assess the relative effect of TRT on glycolipid metabolism among hypogonadal men with T2DM.

Methods

: Electronic literature searches of the Cochrane Library, PubMed, MEDLINE, and EMBASE databases were conducted, up to the end of October 2020. Only studies that used randomized controlled trials (RCTs) were included in our systematic review. Main outcome measures From these studies, we extracted certain outcomes including changes in insulin resistance, glucose metabolism, and lipid parameters.

Results

There were a total of 8 studies that met our criteria. Four of these studies either did not have a consistent treatment strategy, or the control groups used untreated patients rather than patients that had been given a placebo. Thus, results from these four studies contributed to the variability in treatment outcomes. In four of the examined RCTs, there was no change in either the dose or the type of antidiabetic medication prescribed. Based on the homeostatic model assessment of insulin resistance, the pooled WMD was −0.34, 95% confidence interval (CI; −1.02, 0.34), P = .33; For fasting plasma glucose, the pooled WMD was −0.27, 95% CI (−1.02, 0.48), P = .48, the pooled WMD for HbA1c% was −0.00, 95% CI (−1.08, 1.08), P = 1.00.

Conclusions

Although certain RCTs showed that TRT improved insulin resistance and glycolipid metabolism when compared with the placebo or untreated control groups, these findings may partly be due to changes in antidiabetic therapy during the course of the study. In the current meta-analysis, analyses showed that TRT did not significantly improve insulin resistance or glycolipid metabolism. Future studies need to be rigorous in design and delivery, and comprehensive descriptions of all aspects of their methods should be included to further enable a more accurate appraisal and interpretation of the results.
Comparison of Radiographic, Ultrasound, and Magnetic Resonance Imaging for the Detection of Retained Stingray Barb: A Cadaveric Study
Authors: Docter Taylor A. , Altschuh Lauren B. , Medak Anthony J. , Statum Sheronda M. , Chung Christine B. , Van Hoesen Karen B. , Coffey Christanne H.
Published: July 2021

Introduction

Stingray envenomations are a common marine animal injury for which it is important to identify and remove retained barbs to prevent secondary infection. The optimal imaging modality in stingray foreign body detection is not well characterized in the existing literature. In this study, we compared the accuracy of plain radiography, ultrasound, and magnetic resonance imaging (MRI) in detecting stingray barbs in the human foot and ankle.

Methods

This cadaveric study included a 1:1 randomization to the presence or absence of barbs in 24 sample injuries of human cadaveric foot and ankle specimens. Physicians trained in emergency medicine and radiology performed ultrasound examinations on each specimen and interpreted the presence or absence of a barb. Participants also interpreted x-ray images in the same manner. MRI scans were separately interpreted by a musculoskeletal radiology attending. Data were analyzed using McNemar’s test.

Results

The 19 participants included 14 (74%) trained in emergency medicine and 5 (26%) trained in radiology. Forty-seven percent were residents, 42% faculty, and 11% fellows. X-ray was associated with the highest sensitivity of 94% for the identification of a retained barb, followed by MRI (83%) and ultrasound (70%). MRI was associated with the highest specificity of 100%, followed by x-ray (98%) and ultrasound (73%).

Conclusions

Retained stingray barbs can lead to secondary infection after envenomation. In human cadaveric specimens, x-ray demonstrated the highest sensitivity, MRI demonstrated the highest specificity, and ultrasound demonstrated lower sensitivity and specificity.
Elite Decision-making and International Law: Promises and Perils of the Behavioral Revolution
Authors: Hafner-Burton Emilie M.
Published: July 2021

A growing body of research applies behavioral approaches to the study of international law, mainly by studying convenience samples of students or other segments of the general public. Alongside the promises of this agenda are concerns about applying findings from non-elite populations to the people, and groups of people, charged with most real-world decision-making in the domain of law and governance. This concern is compounded by the fact that it is extremely difficult to recruit these actual decision-makers in a way that allows for direct study.
Wisdom of affect? Emotion, environment, and the future of resource extraction
Authors: Sörlin Sverker
Published: July 2021

The “Arctic Uchronotopias” special issue of Polar Record is an important contribution to scholarly reflection on resource extraction. The ideas, perspectives, and empirical cases that we encounter have significance for extractivism wherever it takes place, both inside and outside of the Arctic region. To see extractivism through an Arctic lens is particularly useful since it brings up many of the issues that are often at stake in extraction activities, but not always at the same time: geopolitics, transboundary relations, environmental and climate impacts, cultural and natural heritage, indigenous relations, rights issues, local and regional development, and lives and fates of communities. Above all, these papers bring out the full spectrum of issues and tensions related to ongoing major global shifts, such as the Great Acceleration and Overheating, and those transformations of which resource extraction forms a major part. The research presented in Arctic Uchronotopias demonstrates that affect and emotions have explanatory value in the geopolitics of Arctic resource extraction. It also shows that emotional and cognitive experience and wisdom carry values and properties that conventional Environmental Impact Assessments and other technologies of evaluation and decision-making can capture.
Critical Observations of Gaseous Elemental Mercury Air‐Sea Exchange
Authors: Osterwalder S. , Nerentorp M. , Zhu W. , Jiskra M. , Nilsson E. , Nilsson M. B. , Rutgersson A. , Soerensen A. L. , Sommar J. , Wallin M. B. , Wängberg I. , Bishop K.
Published: July 2021

Air‐sea exchange of gaseous elemental mercury (Hg0) is not well constrained, even though it is a major component of the global Hg cycle. Lack of Hg0 flux measurements to validate parameterizations of the Hg0 transfer velocity contributes to this uncertainty. We measured the Hg0 flux on the Baltic Sea coast using micrometeorological methods (gradient‐based and relaxed eddy accumulation [REA]) and also simulated the flux with a gas exchange model. The coastal waters were typically supersaturated with Hg0 (mean ± 1σ = 13.5 ± 3.5 ng m−3; ca. 10% of total Hg) compared to the atmosphere (1.3 ± 0.2 ng m−3). The Hg0 flux calculated using the gas exchange model ranged from 0.1–1.3 ng m−2 h−1 (10th and 90th percentile) over the course of the campaign (May 10–June 20, 2017) and showed a distinct diel fluctuation. The mean coastal Hg0 fluxes determined with the two gradient‐based approaches and REA were 0.3, 0.5, and 0.6 ng m−2 h−1, respectively. In contrast, the mean open sea Hg0 flux measured with REA was larger (6.3 ng m−2 h−1). The open sea Hg0 flux indicated a stronger wind speed dependence for the Hg0 transfer velocity compared to commonly used parameterizations. Although based on a limited data set, we suggest that the wind speed dependence of the Hg0 transfer velocity is more consistent with gases that have less water solubility than CO2 (e.g., O2). These pioneering flux measurements using micrometeorological techniques show that more such measurements would improve our understanding of air‐sea Hg exchange.
An Initial Assessment of the Contribution of Fresh Submarine Ground Water Discharge to the Alkalinity Budget of the Mediterranean Sea
Authors: Kolker D. , Bookman R. , Herut B. , David N. , Silverman J.
Published: July 2021

Excess total alkalinity (TA) of Mediterranean Sea (MS) seawater relative to its Atlantic origin has been attributed to high inputs from major rivers and the Black Sea. Submarine groundwater discharge (SGD), which was recently shown to be an important source of nutrients to the MS, may also be an important source of TA to the MS. During 2015–2017, water samples were taken from a shoreline groundwater spring near Tel‐Shikmona, northern Israel, and analyzed for TA, salinity, and dissolved inorganic nutrients. Spring water TA varied seasonally between a low of 3,919 and a high of 7,148 µmol kg−1 in the summer and winter, respectively. Long‐term records from a nearby monitoring site indicate that wintertime coastal water TA is positively correlated with annual rainfall rates. Based on the Tel‐Shikmona groundwater spring measurements and other measurements from the MS region reported in the literature, we estimated that the TA flux from the fresh component of SGD (FSGD) in this region is 22%–37% and 17%–30% of the riverine and Black Sea TA fluxes to the MS, respectively.
Effects of Heterogeneous Stream‐Groundwater Exchange on the Source Composition of Stream Discharge and Solute Load
Authors: Zhang Zhi‐Yuan , Schmidt Christian , Nixdorf Erik , Kuang Xingxing , Fleckenstein Jan H.
Published: July 2021

The exchange of water and solutes between the stream and groundwater along a stream network affects the source composition of discharge and solute load in the stream. To date, this hydrologic turnover has only been analyzed with respect to the exchange of water. In this study, we extend the concept of hydrologic turnover to solutes and analyze the effects of different hydrologic conditions on the spatial patterns and magnitude of exchange fluxes. Based on a coupled stream‐groundwater model built in MODFLOW using the Streamflow‐routing package, we simulated stream‐groundwater exchange along a stream of 30 km in length and evaluated the evolution of stream water source composition under different precipitation and streamflow conditions. Results show that even for highly variable hydrologic conditions, the direction of stream‐groundwater exchange (loss/gain) remained unchanged in consistently gaining or losing reaches, but changed in interspersed transitional reaches. The comparison between the source composition of discharge and nitrate load in stream water revealed a decoupling of discharge and solute load contribution from groundwater to the stream, as zones of high water gains do not necessarily coincide with zones of high solute concentrations. Overall, nearly 80% of total groundwater contributions to the outflow of water from the catchment were generated over only 20% of the total stream length. Our research highlights the importance of distinguishing water and solute load contributions to streams. This in turn implies that to reduce groundwater‐borne nutrient loads to streams, measures need to focus on the specific reaches with highest load contributions.
Insight Into the Early Exhumation of the Cycladic Blueschist Unit, Syros, Greece: Combined Application of Zoned Garnet Geochronology, Thermodynamic Modeling, and Quartz Elastic Barometry
Authors: Gorce Jennifer S. , Caddick Mark J. , Baxter Ethan F. , Dragovic Besim , Schumacher John C. , Bodnar Robert J. , Kendall Jamie F.
Published: July 2021

Constraining conditions and mechanisms of the early stages of exhumation from within subduction zones is challenging. Although pressure, temperature, and age can be inferred from the exhumed rock record, it is generally difficult to derive each of these parameters from any single rock, thus demanding assumptions that diverse data from multiple samples can be safely combined into a single pressure‐temperature‐time (P‐T‐t) path that might then be used to infer tectonic context and mechanisms of exhumation. Here, we present new thermobarometric and geochronologic information preserved in a single sample from Syros, Greece, to deduce the conditions and rates of the earliest phase of exhumation as a part of the well‐preserved high‐pressure metamorphic rocks of the Cycladic Blueschist Unit (CBU). The sample studied here is a garnet‐bearing, quartz‐mica schist that records two distinct metamorphic events. Results from thermodynamic models and quartz‐in‐garnet elastic geobarometry show that metamorphic garnet cores formed as P‐T conditions evolved from ∼485°C and 2.2 GPa to 530°C and 2.0 GPa, and that garnet rims formed as conditions evolved from ∼560°C and 2.1 GPa to ∼550°C and 1.6 GPa. Sm‐Nd geochronology on garnet cores and rims yields ages of 45.3 ± 1.0 and 40.5 ± 1.9 Ma, respectively, thus indicating a 4.8 ± 2.1 Myr growth span. Given the decompression path calculated based on garnet core and rim P‐T estimates, we conclude that the distinct phases of garnet growth preserve evidence of the initial exhumation of portions of the CBU.
A Laboratory Perspective on the Gutenberg‐Richter and Characteristic Earthquake Models
Authors: Korkolis Evangelos , Niemeijer André R. , Paulssen Hanneke , Trampert Jeannot
Published: July 2021

Probabilistic seismic hazard analysis (PSHA) is the standard method used for designing earthquake‐resistant infrastructure. In recent years, several unexpected and destructive earthquakes have sparked criticism of the PSHA methodology. The seismological part of the problem is the true frequency‐magnitude distribution of regional seismicity. Two major models exist, the Gutenberg‐Richter (G‐R) and the Characteristic Earthquake (CE) model, but it is difficult to choose between them. That is because the instrumental, historical, and paleoseimological data available are limited in many regions of interest. Here, we demonstrate how a friction experiment on aggregates of glass beads can produce both regular (CE equivalent) and irregular (G‐R equivalent) stick‐slip. Using a new rotary shear apparatus we produced and analyzed large catalogs of acoustic emission (AE) events related to stick‐slip. The distributions of AE sizes, interevent times, and interevent distances were found to be sensitive to particle size and the applied normal stress, and, to a lesser degree, the stiffness of the loading apparatus. More importantly, the system spontaneously switched behavior for short periods of time. In the context of PSHA, if faults are able to switch behavior as our experimental system does, then justifying the choice of either the CE or the G‐R model is impossible based on existing observations.
The Contribution of a Newly Unraveled 64 Years Common Oscillation on the Estimate of Present‐Day Global Mean Sea Level Rise
Authors: Ding Hao , Jin TaoYong , Li JianCheng , Jiang WeiPing
Published: July 2021

The multidecadal fluctuations in sea level changes play an important role in the exact quantification of present‐day global mean sea level (GMSL) rise and its acceleration. Here, we use an array processing technique (optimal sequence estimation) to analyze 44 global tide gauge (TG) sea‐level records with identical January 1933–December 2019 data spans. The results reveal for the first time a common 64.0 ± 3 years periodic oscillation with a spherical harmonic Y21 spatial pattern. Based on the estimated equivalent “excitation” amplitude (A = 47.7 ± 2 mm) and phase (φ = −0.406 rad), we constructed a global model for this 64 years sea‐level fluctuation. The complex amplitudes of the extracted ∼64 years fluctuation from 94 TG records with different data spans, and of two GMSL time series are consistent with the corresponding results predicted by the constructed model using the stacking results using 44 TGs. We find that the 64 years oscillation has significant contributions on the estimate of reconstructed GMSL trend: it contributed about 24% to the sea‐level trend during 1993–2014 and cause a relative deceleration during 2024–2055; while it contributes slightly to the satellite‐based GMSL trend estimates during 1993–2020. We confirm that this 64 years signal is not originated from the Earth's polar motion; however, it has good consistency with the Earth's magnetic field dipole changes, and with the ∼65 years oscillation in the ΔLOD, which suggests that this 64 years signal could come from core motions. We believe our results unravel a new understanding of the mechanisms of GMSL's long‐term fluctuations within the Earth system.
Forecasting the Remaining Duration of an Ongoing Solar Flare
Authors: Reep Jeffrey W. , Barnes Will T.
Published: July 2021

The solar X‐ray irradiance is significantly heightened during the course of a solar flare, which can cause radio blackouts due to ionization of the atoms in the ionosphere. As the duration of a solar flare is not related to the size of that flare, it is not directly clear how long those blackouts can persist. Using a random forest regression model trained on data taken from X‐ray light curves, we have developed a direct forecasting method that predicts how long the event will remain above background levels. We test this on a large collection of flares observed with GOES‐15, and show that it generally outperforms simple linear regression, giving a median error of less than 2 min for the approximate end time of a flare. This random forest model is computationally light enough to be performed in real time, allowing for the prediction to be made during the course of a flare.
Functional genomics for breast cancer drug target discovery
Authors: Yoshimaru Tetsuro , Nakamura Yusuke , Katagiri Toyomasa
Published: July 2021

Breast cancer is a heterogeneous disease that develops through a multistep process via the accumulation of genetic/epigenetic alterations in various cancer-related genes. Current treatment options for breast cancer patients include surgery, radiotherapy, and chemotherapy including conventional cytotoxic and molecular-targeted anticancer drugs for each intrinsic subtype, such as endocrine therapy and antihuman epidermal growth factor receptor 2 (HER2) therapy. However, these therapies often fail to prevent recurrence and metastasis due to resistance. Overall, understanding the molecular mechanisms of breast carcinogenesis and progression will help to establish therapeutic modalities to improve treatment. The recent development of comprehensive omics technologies has led to the discovery of driver genes, including oncogenes and tumor-suppressor genes, contributing to the development of molecular-targeted anticancer drugs. Here, we review the development of anticancer drugs targeting cancer-specific functional therapeutic targets, namely, MELK (maternal embryonic leucine zipper kinase), TOPK (T-lymphokine-activated killer cell-originated protein kinase), and BIG3 (brefeldin A-inhibited guanine nucleotide-exchange protein 3), as identified through comprehensive breast cancer transcriptomics.
School nutrition laws in the US: do they influence obesity among youth in a racially/ethnically diverse state?
Authors: Sanchez-Vaznaugh Emma V. , Matsuzaki Mika , Braveman Paula , Acosta Maria Elena , Alexovitz Kelsey , Sallis James F. , Peterson Karen E. , Sánchez Brisa N.
Published: July 2021

Background/objectives

Little is known about the separate or combined effects of state and national nutrition policies regulating food and beverages in schools on child overweight/obesity (OV/OB) and related racial/ethnic disparities. We investigated the influence of school nutrition policies enacted in California, independently and in combination with the United States’ national policy “Healthy Hunger Free Kids Act” (HHFKA) on childhood OV/OB and racial/ethnic disparities.

Subjects/methods

An interrupted time series design was used with data from 12,363,089 child-level records on 5th- and 7th-graders in California public schools to estimate sex- and racial/ethnic-specific time trends in OV/OB prevalence during three periods: before the California nutrition policies (2002–2004); when only California policies were in effect (2005–2012); and when they were in effect simultaneously with HHFKA (2013–2016).

Results

Before the state’s policies, OV/OB prevalence increased annually among children in most subgroups. Improvements in OV/OB trends were observed for almost all groups after the California policies were in effect, with further improvements after the addition of HFFKA. The total change in annual log-odds of OV/OB, comparing the periods with both state and federal policies versus no policies, ranged from −0.08 to −0.01 and varied by grade, sex, and race/ethnicity. Within each sex and grade, the greatest changes were among African-American (−0.08 to −0.02, all p < 0.05) followed by Latino children (−0.06 to −0.01, all p < 0.05). Although disparities narrowed among these groups versus White children after the dual policy period, disparities remained large.

Conclusions

State and national nutrition policies for schools may have contributed to containing the upward trend in childhood OV/OB and racial/ethnic OV/OB disparities within California. However, sizable OV/OB prevalence and disparities persist. To end the epidemic, promote healthy weight and increase health equity, future efforts should strengthen state and national policies to improve food quality in schools, particularly those serving populations with the highest OV/OB prevalence.
Anti-scattering light focusing by fast wavefront shaping based on multi-pixel encoded digital-micromirror device
Authors: Yang Jiamiao , He Qiaozhi , Liu Linxian , Qu Yuan , Shao Rongjun , Song Bowen , Zhao Yanyu
Published: July 2021

Speed and enhancement are the two most important metrics for anti-scattering light focusing by wavefront shaping (WS), which requires a spatial light modulator with a large number of modulation modes and a fast speed of response. Among the commercial modulators, the digital-micromirror device (DMD) is the sole solution providing millions of modulation modes and a pattern rate higher than 20 kHz. Thus, it has the potential to accelerate the process of anti-scattering light focusing with a high enhancement. Nevertheless, modulating light in a binary mode by the DMD restricts both the speed and enhancement seriously. Here, we propose a multi-pixel encoded DMD-based WS method by combining multiple micromirrors into a single modulation unit to overcome the drawbacks of binary modulation. In addition, to efficiently optimize the wavefront, we adopted separable natural evolution strategies (SNES), which could carry out a global search against a noisy environment. Compared with the state-of-the-art DMD-based WS method, the proposed method increased the speed of optimization and enhancement of focus by a factor of 179 and 16, respectively. In our demonstration, we achieved 10 foci with homogeneous brightness at a high speed and formed W- and S-shape patterns against the scattering medium. The experimental results suggest that the proposed method will pave a new avenue for WS in the applications of biomedical imaging, photon therapy, optogenetics, dynamic holographic display, etc.
Retinopathy of prematurity shows alterations in Vegfa164 isoform expression
Authors: Mezu-Ndubuisi Olachi J. , Song Yong-Seok , Macke Erica , Johnson Hailey , Nwaba Ginika , Ikeda Akihiro , Sheibani Nader
Published: July 2021

Background

Pathologic ocular neovascularization in retinopathy of prematurity (ROP) and other proliferative retinopathies are characterized by dysregulation of vascular endothelial growth factor-A (VEGF-A). A study of Vegfa isoform expression during oxygen-induced ischemic retinopathy (OIR) may enhance our understanding of Vegf dysregulation.

Methods

Following induction of OIR, immunohistochemistry and polymerase chain reaction (PCR) was performed on room air (RA) and OIR mice.

Results

Total Vegfa messenger RNA (mRNA) expression was stable in RA mice, but increased in OIR mice with a peak at postnatal day 17 (P17), before returning to RA levels. Vegfa164a expression was similar in both OIR and RA mice at P10 (Phase 1 OIR), but 2.4-fold higher in OIR mice compared to RA mice at P16 (Phase 2 OIR). At P10, Vegfa164b mRNA was similar in OIR vs RA mice, but was expressed 2.5-fold higher in OIR mice compared to RA mice at P16. At P10 and P16, Vegfr2/Vegfr1 expression was increased in OIR mice compared to RA mice. Increased activation of microglia was seen in OIR mice.

Conclusions

Vegfa164a, Vegfa164b, and Vegfr1 were overexpressed in OIR mice, leading to abnormal signaling and angiogenesis. Further studies of mechanisms of Vegf dysregulation may lead to novel therapies for ROP and other proliferative retinopathies.

Impact

Vegfa164 has two major isoforms, a proangiogenic, Vegfa164a, and an antiangiogenic, Vegfa164b, with opposing receptors, inhibitory Vegfr1, and stimulatory Vegfr2, but their role in OIR is unclear.

In Phase 1 OIR, both isoforms and receptors are expressed similarly.

In Phase 2 OIR, both isoforms are overexpressed, with an increased ratio of inhibitory Vegfr1.

Modulation of angiogenesis by Vegf regulation enables pruning of excess angiogenesis during physiology, but results in ineffective angiogenesis during OIR. Knowledge of VEGF dysregulation may have novel therapeutic implications in the management of ROP and retinal proliferative diseases.
Sulfate differentially stimulates but is not respired by diverse anaerobic methanotrophic archaea
Authors: Yu Hang , Skennerton Connor T , Chadwick Grayson L , Leu Andy O , Aoki Masataka , Tyson Gene W , Orphan Victoria J
Published: July 2021

Sulfate-coupled anaerobic oxidation of methane (AOM) is a major methane sink in marine sediments. Multiple lineages of anaerobic methanotrophic archaea (ANME) often coexist in sediments and catalyze this process syntrophically with sulfate-reducing bacteria (SRB), but the potential differences in ANME ecophysiology and mechanisms of syntrophy remain unresolved. A humic acid analog, anthraquinone 2,6-disulfonate (AQDS), could decouple archaeal methanotrophy from bacterial sulfate reduction and serve as the terminal electron acceptor for AOM (AQDS-coupled AOM). Here in sediment microcosm experiments, we examined variations in physiological response between two co-occurring ANME-2 families (ANME-2a and ANME-2c) and tested the hypothesis of sulfate respiration by ANME-2. Sulfate concentrations as low as 100 µM increased AQDS-coupled AOM nearly 2-fold matching the rates of sulfate-coupled AOM. However, the SRB partners remained inactive in microcosms with sulfate and AQDS and neither ANME-2 families respired sulfate, as shown by their cellular sulfur contents and anabolic activities measured using nanoscale secondary ion mass spectrometry. ANME-2a anabolic activity was significantly higher than ANME-2c, suggesting that ANME-2a was primarily responsible for the observed sulfate stimulation of AQDS-coupled AOM. Comparative transcriptomics showed significant upregulation of ANME-2a transcripts linked to multiple ABC transporters and downregulation of central carbon metabolism during AQDS-coupled AOM compared to sulfate-coupled AOM. Surprisingly, genes involved in sulfur anabolism were not differentially expressed during AQDS-coupled AOM with and without sulfate amendment. Collectively, this data indicates that ANME-2 archaea are incapable of respiring sulfate, but sulfate availability differentially stimulates the growth and AOM activity of different ANME lineages.
Seasonal niche differentiation among closely related marine bacteria
Authors: Auladell Adrià , Barberán Albert , Logares Ramiro , Garcés Esther , Gasol Josep M , Ferrera Isabel
Published: July 2021

Bacteria display dynamic abundance fluctuations over time in marine environments, where they play key biogeochemical roles. Here, we characterized the seasonal dynamics of marine bacteria in a coastal oligotrophic time series station, tested how similar the temporal niche of closely related taxa is, and what are the environmental parameters modulating their seasonal abundance patterns. We further explored how conserved the niche is at higher taxonomic levels. The community presented recurrent patterns of seasonality for 297 out of 6825 amplicon sequence variants (ASVs), which constituted almost half of the total relative abundance (47%). For certain genera, niche similarity decreased as nucleotide divergence in the 16S rRNA gene increased, a pattern compatible with the selection of similar taxa through environmental filtering. Additionally, we observed evidence of seasonal differentiation within various genera as seen by the distinct seasonal patterns of closely related taxa. At broader taxonomic levels, coherent seasonal trends did not exist at the class level, while the order and family ranks depended on the patterns that existed at the genus level. This study identifies the coexistence of closely related taxa for some bacterial groups and seasonal differentiation for others in a coastal marine environment subjected to a strong seasonality.
Response to substrate limitation by a marine sulfate-reducing bacterium
Authors: Marietou Angeliki , Kjeldsen Kasper U , Glombitza Clemens , Jørgensen Bo Barker
Published: July 2021

Sulfate-reducing microorganisms (SRM) in subsurface sediments live under constant substrate and energy limitation, yet little is known about how they adapt to this mode of life. We combined controlled chemostat cultivation and transcriptomics to examine how the marine sulfate reducer, Desulfobacterium autotrophicum, copes with substrate (sulfate or lactate) limitation. The half-saturation uptake constant (Km) for lactate was 1.2 µM, which is the first value reported for a marine SRM, while the Km for sulfate was 3 µM. The measured residual lactate concentration in our experiments matched values observed in situ in marine sediments, supporting a key role of SRM in the control of lactate concentrations. Lactate limitation resulted in complete lactate oxidation via the Wood–Ljungdahl pathway and differential overexpression of genes involved in uptake and metabolism of amino acids as an alternative carbon source. D. autotrophicum switched to incomplete lactate oxidation, rerouting carbon metabolism in response to sulfate limitation. The estimated free energy was significantly lower during sulfate limitation (−28 to −33 kJ mol−1 sulfate), suggesting that the observed metabolic switch is under thermodynamic control. Furthermore, we detected the upregulation of putative sulfate transporters involved in either high or low affinity uptake in response to low or high sulfate concentration.
Single-cell transcriptome and TCR profiling reveal activated and expanded T cell populations in Parkinson’s disease
Authors: Wang Pingping , Yao Lifen , Luo Meng , Zhou Wenyang , Jin Xiyun , Xu Zhaochun , Yan Shi , Li Yiqun , Xu Chang , Cheng Rui , Huang Yan , Lin Xiaoyu , Ma Kexin , Cao Huimin , Liu Hongxin , Xue Guangfu , Han Fang , Nie Huan , Jiang Qinghua
Published: July 2021

Given the chronic inflammatory nature of Parkinson’s disease (PD), T cell immunity may be important for disease onset. Here, we performed single-cell transcriptome and TCR sequencing, and conducted integrative analyses to decode composition, function and lineage relationship of T cells in the blood and cerebrospinal fluid of PD. Combined expression and TCR-based lineage tracking, we discovered a large population of CD8+ T cells showing continuous progression from central memory to terminal effector T cells in PD patients. Additionally, we identified a group of cytotoxic CD4+ T cells (CD4 CTLs) remarkably expanded in PD patients, which derived from Th1 cells by TCR-based fate decision. Finally, we screened putative TCR–antigen pairs that existed in both blood and cerebrospinal fluid of PD patients to provide potential evidence for peripheral T cells to participate in neuronal degeneration. Our study provides valuable insights and rich resources for understanding the adaptive immune response in PD.
Three epitope-distinct human antibodies from RenMab mice neutralize SARS-CoV-2 and cooperatively minimize the escape of mutants
Authors: Nie Jianhui , Xie Jingshu , Liu Shuo , Wu Jiajing , Liu Chuan , Li Jianhui , Liu Yacui , Wang Meiyu , Zhao Huizhen , Zhang Yabo , Yao Jiawei , Chen Lei , Shen Yuelei , Yang Yi , Wang Hong-Wei , Wang Youchun , Huang Weijin
Published: July 2021

Coronavirus disease 2019 (COVID-19), a pandemic disease caused by the newly emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused more than 3.8 million deaths to date. Neutralizing antibodies are effective therapeutic measures. However, many naturally occurring mutations at the receptor-binding domain (RBD) have emerged, and some of them can evade existing neutralizing antibodies. Here, we utilized RenMab, a novel mouse carrying the entire human antibody variable region, for neutralizing antibody discovery. We obtained several potent RBD-blocking antibodies and categorized them into four distinct groups by epitope mapping. We determined the involved residues of the epitope of three representative antibodies by cryo-electron microscopy (Cryo-EM) studies. Moreover, we performed neutralizing experiments with 50 variant strains with single or combined mutations and found that the mixing of three epitope-distinct antibodies almost eliminated the mutant escape. Our study provides a sound basis for the rational design of fully human antibody cocktails against SARS-CoV-2 and pre-emergent coronaviral threats.
Hyperprolinemia type I caused by homozygous p.T466M mutation in PRODH
Authors: Hama Rina , Kido Jun , Sugawara Keishin , Nakamura Toshiro , Nakamura Kimitoshi
Published: July 2021

Hyperprolinemia type I (HPI) is an autosomal recessive metabolic disorder caused by defects in proline oxidase. We herein describe a case of a patient with HPI and harboring the NM_016335.4 (PRODH_v001):c.1397 C > T (p.T466M) mutation and polymorphisms in thePRODHgene, as detected by plasma amino acid analysis and Sanger sequencing. The patient presented with short stature, carbohydrate-rich dietary preferences, and mild intellectual disability that was suggestive of a neurodevelopmental or learning disorder.
Novel MSX1 frameshift mutation in a Japanese family with nonsyndromic oligodontia
Authors: Adachi Junya , Aoki Yoshihiko , Tatematsu Tadashi , Goto Hiroki , Nakayama Atsuo , Nishiyama Takeshi , Takahashi Katsu , Sana Masatoshi , Ota Akiko , Machida Junichiro , Nagao Toru , Tokita Yoshihito
Published: July 2021

Congenital tooth agenesis is a common anomaly in humans. We investigated the etiology of human tooth agenesis by exome analysis in Japanese patients, and found a previously undescribed heterozygous deletion (NM_002448.3(MSX1_v001):c.433_449del) in the first exon of the MSX1 gene. The deletion leads to a frameshift and generates a premature termination codon. The truncated form of MSX1, namely, p.(Trp145Leufs*24) lacks the homeodomain, which is crucial for transcription factor function.
Reversible electroadhesion of hydrogels to animal tissues for suture-less repair of cuts or tears
Authors: Borden Leah K. , Gargava Ankit , Raghavan Srinivasa R.
Published: July 2021

Electroadhesion, i.e., adhesion induced by an electric field, occurs between non-sticky cationic and anionic hydrogels. Here, we demonstrate electroadhesion between cationic gels and animal (bovine) tissues. When gel and tissue are placed under an electric field (DC, 10 V) for 20 s, the pair strongly adhere, and the adhesion persists indefinitely thereafter. Applying the DC field with reversed polarity eliminates the adhesion. Electroadhesion works with the aorta, cornea, lung, and cartilage. We demonstrate the use of electroadhesion to seal cuts or tears in tissues or model anionic gels. Electroadhered gel-patches provide a robust seal over openings in bovine aorta, and a gel sleeve is able to rejoin pieces of a severed gel tube. These studies raise the possibility of using electroadhesion in surgery while obviating the need for sutures. Advantages include the ability to achieve adhesion on-command, and moreover the ability to reverse this adhesion in case of error.
Temperature heterogeneity correlates with intraspecific variation in physiological flexibility in a small endotherm
Authors: Stager Maria , Senner Nathan R. , Swanson David L. , Carling Matthew D. , Eddy Douglas K. , Greives Timothy J. , Cheviron Zachary A.
Published: July 2021

Phenotypic flexibility allows individuals to reversibly modify trait values and theory predicts an individual’s relative degree of flexibility positively correlates with the environmental heterogeneity it experiences. We test this prediction by integrating surveys of population genetic and physiological variation with thermal acclimation experiments and indices of environmental heterogeneity in the Dark-eyed Junco (Junco hyemalis) and its congeners. We combine field measures of thermogenic capacity for 335 individuals, 22,006 single nucleotide polymorphisms genotyped in 181 individuals, and laboratory acclimations replicated on five populations. We show thatJuncopopulations: (1) differ in their thermogenic responses to temperature variation in the field; (2) harbor allelic variation that also correlates with temperature heterogeneity; and (3) exhibit intra-specific variation in thermogenic flexibility in the laboratory that correlates with the heterogeneity of their native thermal environment. These results provide comprehensive support that phenotypic flexibility corresponds with environmental heterogeneity and highlight its importance for coping with environmental change.
Refractoriness of STING therapy is relieved by AKT inhibitor through effective vascular disruption in tumour
Authors: Jeong Seung-hwan , Yang Myung Jin , Choi Seunghyeok , Kim JungMo , Koh Gou Young
Published: July 2021

Stimulator of interferon genes (STING) promotes anti-tumour immunity by linking innate and adaptive immunity, but it remains unclear how intratumoural treatment with STING agonists yields anti-tumour effects. Here we demonstrate that intratumoural injection of the STING agonist cGAMP induces strong, rapid, and selective apoptosis of tumour endothelial cells (ECs) in implanted LLC tumour, melanoma and breast tumour, but not in spontaneous breast cancer and melanoma. In both implanted and spontaneous tumours, cGAMP greatly increases TNFα from tumour-associated myeloid cells. However, compared to spontaneous tumour ECs, implanted tumour ECs are more vulnerable to TNFα-TNFR1 signalling-mediated apoptosis, which promotes effective anti-tumour activity. The spontaneous tumour’s refractoriness to cGAMP is abolished by co-treatment with AKT 1/2 inhibitor (AKTi). Combined treatment with cGAMP and AKTi induces extensive tumour EC apoptosis, leading to extensive tumour apoptosis and marked growth suppression of the spontaneous tumour. These findings propose an advanced avenue for treating primary tumours that are refractory to single STING agonist therapy.
A generalizable and accessible approach to machine learning with global satellite imagery
Authors: Rolf Esther , Proctor Jonathan , Carleton Tamma , Bolliger Ian , Shankar Vaishaal , Ishihara Miyabi , Recht Benjamin , Hsiang Solomon
Published: July 2021

Combining satellite imagery with machine learning (SIML) has the potential to address global challenges by remotely estimating socioeconomic and environmental conditions in data-poor regions, yet the resource requirements of SIML limit its accessibility and use. We show that a single encoding of satellite imagery can generalize across diverse prediction tasks (e.g., forest cover, house price, road length). Our method achieves accuracy competitive with deep neural networks at orders of magnitude lower computational cost, scales globally, delivers label super-resolution predictions, and facilitates characterizations of uncertainty. Since image encodings are shared across tasks, they can be centrally computed and distributed to unlimited researchers, who need only fit a linear regression to their own ground truth data in order to achieve state-of-the-art SIML performance.