bluuebunny/crossref_metadata_2025 huggingface dataset:
38766 Massively Parallel Reporter Assay Reveals Functional Impact of 3™-UTR SNPs Associated with Neurological and Psychiatric Disorders
Authors: Chen Andy B. , Thapa Kriti , Gao Hongyu , Reiter Jill L. , Zhang Junjie , Xuei Xiaoling , Gu Hongmei , Wang Yue , Edenberg Howard J. , Liu Yunlong
Published: March 2021

ABSTRACT IMPACT: Screening the effect of thousands of non-coding genetic variants will help identify variants important in the etiology of diseases OBJECTIVES/GOALS: Massively parallel reporter assays (MPRAs) can experimentally evaluate the impact of genetic variants on gene expression. In this study, our objective was to systematically evaluate the functional activity of 3’-UTR SNPs associated with neurological disorders and use those results to help understand their contributions to disease etiology. METHODS/STUDY POPULATION: To choose variants to evaluate with the MPRA, we first gathered SNPs from the GWAS Catalog that were associated with any neurological disorder trait with p-value < 10-5. For each SNP, we identified the region that was in linkage disequilibrium (r2 > 0.8) and retrieved all the common 3’-UTR SNPs (allele-frequency > 0.05) within that region. We used an MPRA to measure the impact of these 3’-UTR variants in SH-SY5Y neuroblastoma cells and a microglial cell line. These results were then used to train a deep-learning model to predict the impact of variants and identify features that contribute to the predictions. RESULTS/ANTICIPATED RESULTS: Of the 13,515 3’-UTR SNPs tested, 400 and 657 significantly impacted gene expression in SH-SY5Y and microglia, respectively. Of the 84 SNPs significantly impacted in both cells, the direction of impact was the same in 81. The direction of eQTL in GTEx tissues agreed with the assay SNP effect in SH-SY5Y cells but not microglial cells. The deep-learning model predicted sequence activity level correlated with the experimental activity level (Spearman’s corr = 0.45). The deep-learning model identified several predictive motifs similar to motifs of RNA-binding proteins. DISCUSSION/SIGNIFICANCE OF FINDINGS: This study demonstrates that MPRAs can be used to evaluate the effect of non-coding variants, and the results can be used to train a machine learning model and interpret its predictions. Together, these can help identify causal variants and further understand the etiology of diseases.
35156 Sensory mechanisms of atypical motor variability and regularity in autism spectrum disorder
Authors: Shafer Robin L. , Wang Zheng , Bartolotti James , Mosconi Matthew W.
Published: March 2021

ABSTRACT IMPACT: This project aims to better understand mechanisms of sensory and motor deficits in individuals with ASD with the goal of informing diagnosis and treatment development. OBJECTIVES/GOALS: Over-reliance on both visual and proprioceptive feedback have both been observed during motor behavior in persons with Autism Spectrum Disorders (ASD), suggesting that separate sensory feedback processes may be selectively altered during different behaviors. The objective of this study is to clarify sensory mechanisms of fine motor control in ASD. METHODS/STUDY POPULATION: Participants with ASD (N=43) and controls (N=23) matched on age (10-20 yrs) and non-verbal IQ completed tests of precision gripping. Participants were instructed to press on force sensors with their index finger and thumb so that a moving bar corresponding to their force output reached and stayed as stable as possible at the level of a stationary target bar. Visual feedback was manipulated by changing the visual gain of the force bar (low, medium and high). The force bar moved more per change in force output at higher gains. Proprioceptive feedback was manipulated by applying 80 Hz tendon vibration at the wrist to induce an illusion of muscle contraction. This was compared to a condition with the tendon vibrator turned off. Force variability (standard deviation) and regularity (sample entropy) were examined. RESULTS/ANTICIPATED RESULTS: Controls showed increased force variability with the tendon vibration on compared to off (t = -3.372, p < 0.001); however, the ASD group showed no difference in force variability between the tendon vibration conditions (t = -0.960, p = 0.338). Individuals with ASD had stronger age-associated reductions in force variability relative to controls across tendon vibrator and gain conditions (Group x Age: t = -4.05, p < .001). The ASD group also had greater age-associated increases in force regularity relative to controls, especially at higher gain levels (Group x Gain Level x Age: t = -3.22, p = 0.001). Unlike the ASD group for whom regularity increased with age in both tendon vibration conditions, controls only showed these age-related gains when the tendon vibrator was off (Group x Vibration Frequency x Age: t = 2.46, p = .014). DISCUSSION/SIGNIFICANCE OF FINDINGS: Our findings indicate that while controls integrate proprioceptive and visual feedback online to accurately adjust fine motor behavior, persons with ASD rely mostly on visual feedback. Our results suggest delayed development of sensory integration and reduced reliance on multisensory feedback during online fine motor control in persons with ASD.
59182 An exploratory analysis of network bridges in translational research; a case study of research grants collaboration networks at University of Rochester School of Medicine and Dentistry
Authors: Nooraie Reza Yousefi , Wayman Elizabeth , Dozier Ann
Published: March 2021

ABSTRACT IMPACT: This analysis helps disentangle various paths to translational collaboration, with implications for departmental capacity building and support. OBJECTIVES/GOALS: Studies that bridge research collaboration networks are cross-disciplinary and translational. We explored the characteristics of researchers and their collaboration patterns in bridging research grants at University of Rochester School of Medicine and Dentistry. METHODS/STUDY POPULATION: the database of sponsored research grants from 2011 to 2018, obtained from an internal University database was transformed into a two-mode network of grant-to-investigator. Grants at 90th percentile and above of normalized two-mode betweenness centrality were defined as ‘bridging grants’. For each grant we extracted the gender, academic rank, academic degree, affiliating department, and centrality-status (being at 75th percentile of degree centrality in one-mode collaboration network) of the Principal Investigator (PI), as well as the number of co-investigators (CI) and the existence of central actor(s) in the research team. RESULTS/ANTICIPATED RESULTS: Out of 2491 sponsored grants, 250 were ‘bridging grants’. The significant predictors of bridging were centrality of PI, existence of central CI(s), PI holding PhD, and larger number of CIs. The PI’s academic rank (being full professor) and gender were not significant predictors. Among bridging grants 79 included both central PI and CIs (central actors group) and 60 included no central actor on the team. In the latter group, more PIs were clinical faculty and fewer were full professors. Network analysis of affiliating departments showed that Medicine was the prominent actor in the central actors group, while the network of no-central actor group was more fragmented with Neurology as central. DISCUSSION/SIGNIFICANCE OF FINDINGS: Widely recognized researchers are more likely to collaborate with each other in bridging studies possibly marginalizing less experienced peers. Bridging grants led by less central researchers, often clinician-scientists, may thrive where supportive culture and departmental facilities exist.
Hearing from the ocean and into the river: the evolution of the inner ear of Platanistoidea (Cetacea: Odontoceti)
Authors: Viglino Mariana , Gaetán Maximiliano , Buono Mónica R. , Fordyce R. Ewan , Park Travis
Published: March 2021

The inner ear of the two higher clades of modern cetaceans (Neoceti) is highly adapted for hearing infrasonic (mysticetes) or ultrasonic (odontocetes) frequencies. Within odontocetes, Platanistoidea comprises a single extant riverine representative, Platanista gangetica, and a diversity of mainly extinct marine species from the late Oligocene onward. Recent studies drawing on features including the disparate tympanoperiotic have not yet provided a consensus phylogenetic hypothesis for platanistoids. Further, cochlear morphology and evolutionary patterns have never been reported. Here, we describe for the first time the inner ear morphology of late Oligocene–early Miocene extinct marine platanistoids and their evolutionary patterns. We initially hypothesized that extinct marine platanistoids lacked a specialized inner ear like P. gangetica and thus, their morphology and inferred hearing abilities were more similar to those of pelagic odontocetes. Our results reveal there is no “typical” platanistoid cochlear type, as the group displays a disparate range of cochlear anatomies, but all are consistent with high-frequency hearing. Stem odontocete Prosqualodon australis and platanistoid Otekaikea huata present a tympanal recess in their cochlea, of yet uncertain function in the hearing mechanism in cetaceans. The more basal morphology of Aondelphis talen indicates it had lower high-frequency hearing than other platanistoids. Finally, Platanista has the most derived cochlear morphology, adding to evidence that it is an outlier within the group and consistent with a >9-Myr-long separation from its sister genus Zarhachis. The evolution of a singular sound production morphology within Platanistidae may have facilitated the survival of Platanista to the present day.
Unicuspid and quadricuspid aortic valves: two case reports and literature review
Authors: Aslan Eyup
Published: March 2021

There are three cusps in a normally developed aortic valve. Abnormal excavation or fusion, during the embryological development of the aortic valve, results in a varying number of cusps. Bicuspid aortic valve is the most common, but more rarely, unicuspid and quadricuspid aortic valves can be seen.

Here, a case of a 16-year-old male with a unicommissural unicuspid aortic valve and a case of a 13-year-old female with a quadricuspid aortic valve were reported.
Using Lego® Serious Play® in Higher Education with Law Students: Encouraging Playfulness and Creativity within Library Workshops
Authors: Wheeler Alan
Published: March 2021

The following article began life as a ten-minute presentation titled ‘Building student engagement brick by brick; using Lego® Serious Play® to explore subject engagement in HE’, presented at BIALL's 2020 virtual conference on 12 June 2020. Since 2016 I have been incorporating Lego® Serious Play® (LSP) within my practice as an academic librarian at Middlesex University. This article will explore how I have embedded LSP into workshops with students and staff, the tactics employed to gain acceptance for using LSP within academic settings and offering some tentative predictions on whether playful approaches will be successful in the current Higher Education (HE) landscape, dominated as we currently are by virtual learning and screen technologies.
Ka-band time-domain multiplexing front-end with minimum switch area utilization on 22 nm fully depleted silicon-on-insulator CMOS technology
Authors: Hietanen Mikko , Rusanen Jere , Aikio Janne P. , Tervo Nuutti , Rahkonen Timo , Pärssinen Aarno
Published: March 2021

A time-domain duplexing radio frequency (RF) front-end with integrated antenna switch, power amplifier (PA), and low noise amplifier (LNA) was developed aiming for fifth-generation communication (5G) applications covering 24–28 GHz frequency range. Antenna switch utilizes pre-existing LNA input matching network together embedded with grounded shunt transistor switch to provide sufficient isolation of receive side from PA. Respectively, high impedance of off-state PA is assumed to achieve acceptable receive performance. Resulting output power is 13.6 dBm with 15 dB of peak small-signal gain at 28 GHz. Maximum average channel power was 4.8 dBm with 100 MHz 64-QAM OFDM signal within 5G adjacent channel power ratio and error vector magnitude specifications. Receive (RX) front-end achieves 5 dB noise figure at 24 GHz and 7 dB of peak gain. Performances of amplifiers degraded only by 2 dB from switch integration. The front-end dissipates 183 and 4.6 mW of power in transmit and receive mode, respectively. The simplistic design method minimizes cost both in circuit area (only 0.19 mm2) and design time making this front-end an attractive alternative in massive phased array applications using 22 nm complementary metal oxide semiconductor (CMOS) fully depleted silicon on insulator process.
Role of testosterone: cortisol ratio in age- and sex-specific cortico-hippocampal development and cognitive performance
Authors: Caccese Christina , Jones Sherri Lee , Ramesh Mrinalini , Yu Ally , Brossard-Racine Marie , Nguyen Tuong-Vi
Published: March 2021

Testosterone (T) and cortisol (C) are steroid hormones that have been argued to play opposing roles in shaping physical and behavioral development in humans. While there is evidence linking T and C to different memory processes during adulthood, it remains unclear how the relative levels of T and C (TC ratio) may influence brain and behavioral development, whether they are influenced by sex of the child, and whether or not they occur as a result of stable changes in brain structure (organizational changes), as opposed to transient changes in brain function (activational changes). As such, we tested for associations among TC ratio, cortico-hippocampal structure, and standardized tests of executive, verbal, and visuo-spatial function in a longitudinal sample of typically developing 4–22-year-old children and adolescents. We found greater TC ratios to be associated with greater coordinated growth (i.e. covariance) between the hippocampus and cortical thickness in several areas primarily devoted to visual function. In addition, there was an age-related association between TC ratio and parieto-hippocampal covariance, as well as a sex-specific association between TC ratio and prefrontal-hippocampal covariance. Differences in brain structure related to TC ratio were in turn associated with lower verbal/executive function, as well as greater attention in tests of visuo-spatial abilities. These results support the notion that TC ratio may shift the balance between top-down (cortex to hippocampus) and bottom-up (hippocampus to cortex) processes, impairing more complex, cortical-based tasks and optimizing visuospatial tasks relying primarily on the hippocampus.
Local and Remote Influences on the Heat Content of Southern Ocean Mode Water Formation Regions
Authors: Boland Emma J. D. , Jones Daniel C. , Meijers Andrew J. S. , Forget Gael , Josey Simon A.
Published: March 2021

The Southern Ocean (SO) is a crucial region for the global ocean uptake of heat and carbon. There are large uncertainties in the observations of fluxes of heat and carbon between the atmosphere and the ocean mixed layer, which lead to large uncertainties in the amount entering into the global overturning circulation. In order to better understand where and when fluxes of heat and momentum have the largest impact on near‐surface heat content, we use an adjoint model to calculate the linear sensitivities of heat content in SO mode water formation regions (MWFRs) to surface fluxes. We find that the heat content of these regions is, in all three basins, most sensitive to same‐winter, local heat fluxes, and to local and remote wind one to eight years (the maximum lead‐time of our simulations) previously. This is supported by sensitivities to potential temperature changes, which reveal the sources of the MWFRs as well as dynamic links with boundary current regions and the Antarctic Circumpolar Current. We use the adjoint sensitivity fields to design a set of targeted perturbation experiments, allowing us to examine the linear and non‐linear responses of the heat content to changes in surface forcing. In these targeted experiments, the heat content is sensitive to both temperature changes and mixed layer volume changes in roughly equal magnitude.
Evidencing the Impact of Climate Change on the Phytoplankton Community of the Mediterranean Sea Through a Bioregionalization Approach
Authors: El Hourany Roy , Mejia Carlos , Faour Ghaleb , Crépon Michel , Thiria Sylvie
Published: March 2021

We revisited the partitioning of the Mediterranean Sea into bioregions by processing satellite Sea Surface Temperature (SST) and Chlorophyll‐a concentration (Chla) from ocean color observations combined with Argo mixed‐layer depth for a period ranging from 2003 up to 2020. This regionalization was performed using an innovative classification based on self‐organizing maps, the so‐called 2S‐SOM. We clustered the Mediterranean Sea waters into seven bioregions governed by specific physical and biogeochemical characteristics. We studied the interannual variability of these bioregions over the 18 years. We showed that the temperature is increasing with a mean rate of 0.4°C per decade. The chlorophyll‐a concentration is quasi constant, but we evidenced a noticeable change in satellite‐derived phytoplankton communities: Diatoms concentration is decreasing while cyanobacteria concentration is increasing. The bioregion trends could be related to global warming. The whole Mediterranean Sea is shifting to an eastern Mediterranean state.
Red Rocks: Using Color to Understand Climate Change
Authors: Mazumdar Ria
Published: March 2021

A recent study on hematite formation during the Triassic may help predict the effects of climate change on contemporary monsoonal environments.
Light People: Professor Donna Strickland
Authors: Wang Hui
Published: March 2021

Editorial

It is rare for an associate professor to win the Nobel Prize for Physics, even more so when she was only the third woman in history to do so, but Dr. Donna Strickland did just that. A permanent smile on her face expressing her friendliness, the fast speaking speed showing her quick thinking, Dr. Strickland is not only a good tutor with strong hands-on ability and high working efficiency in the eyes of her students, but also an optimistic and diligent scholar in the eyes of her peers. Taking an active part in academic societies and the popularization of science, she regards scientific research as “fun”. The famous Canadian physicist Donna Strickland talks exclusively to Light: Science and Applications (light).
PUMA facilitates EMI1-promoted cytoplasmic Rad51 ubiquitination and inhibits DNA repair in stem and progenitor cells
Authors: Kang Jin Wook , Zhan Zhiyan , Ji Guangzhen , Sang Youzhou , Zhou Daohong , Li Yanxin , Feng Haizhong , Cheng Tao
Published: March 2021

Maintenance of genetic stability via proper DNA repair in stem and progenitor cells is essential for the tissue repair and regeneration, while preventing cell transformation after damage. Loss of PUMA dramatically increases the survival of mice after exposure to a lethal dose of ionizing radiation (IR), while without promoting tumorigenesis in the long-term survivors. This finding suggests that PUMA (p53 upregulated modulator of apoptosis) may have a function other than regulates apoptosis. Here, we identify a novel role of PUMA in regulation of DNA repair in embryonic or induced pluripotent stem cells (PSCs) and immortalized hematopoietic progenitor cells (HPCs) after IR. We found that PUMA-deficient PSCs and HPCs exhibited a significant higher double-strand break (DSB) DNA repair activity via Rad51-mediated homologous recombination (HR). This is because PUMA can be associated with early mitotic inhibitor 1 (EMI1) and Rad51 in the cytoplasm to facilitate EMI1-mediated cytoplasmic Rad51 ubiquitination and degradation, thereby inhibiting Rad51 nuclear translocation and HR DNA repair. Our data demonstrate that PUMA acts as a repressor for DSB DNA repair and thus offers a new rationale for therapeutic targeting of PUMA in regenerative cells in the context of DNA damage.
Bacterial cyclic diguanylate signaling networks sense temperature
Authors: Almblad Henrik , Randall Trevor E. , Liu Fanny , Leblanc Katherine , Groves Ryan A. , Kittichotirat Weerayuth , Winsor Geoffrey L. , Fournier Nicolas , Au Emily , Groizeleau Julie , Rich Jacquelyn D. , Lou Yuefei , Granton Elise , Jennings Laura K. , Singletary Larissa A. , Winstone Tara M. L. , Good Nathan M. , Bumgarner Roger E. , Hynes Michael F. , Singh Manu , Stietz Maria Silvina , Brinkman Fiona S. L. , Kumar Ayush , Brassinga Ann Karen Cornelia , Parsek Matthew R. , Tseng Boo Shan , Lewis Ian A. , Yipp Bryan G. , MacCallum Justin L. , Harrison Joe Jonathan
Published: March 2021

Many bacteria use the second messenger cyclic diguanylate (c-di-GMP) to control motility, biofilm production and virulence. Here, we identify a thermosensory diguanylate cyclase (TdcA) that modulates temperature-dependent motility, biofilm development and virulence in the opportunistic pathogenPseudomonas aeruginosa. TdcA synthesizes c-di-GMP with catalytic rates that increase more than a hundred-fold over a ten-degree Celsius change. Analyses using protein chimeras indicate that heat-sensing is mediated by a thermosensitive Per-Arnt-SIM (PAS) domain. TdcA homologs are widespread in sequence databases, and a distantly related, heterologously expressed homolog from the Betaproteobacteria orderGallionellalesalso displayed thermosensitive diguanylate cyclase activity. We propose, therefore, that thermotransduction is a conserved function of c-di-GMP signaling networks, and that thermosensitive catalysis of a second messenger constitutes a mechanism for thermal sensing in bacteria.
Connecting structure to function with the recovery of over 1000 high-quality metagenome-assembled genomes from activated sludge using long-read sequencing
Authors: Singleton Caitlin M. , Petriglieri Francesca , Kristensen Jannie M. , Kirkegaard Rasmus H. , Michaelsen Thomas Y. , Andersen Martin H. , Kondrotaite Zivile , Karst Søren M. , Dueholm Morten S. , Nielsen Per H. , Albertsen Mads
Published: March 2021

Microorganisms play crucial roles in water recycling, pollution removal and resource recovery in the wastewater industry. The structure of these microbial communities is increasingly understood based on 16S rRNA amplicon sequencing data. However, such data cannot be linked to functional potential in the absence of high-quality metagenome-assembled genomes (MAGs) for nearly all species. Here, we use long-read and short-read sequencing to recover 1083 high-quality MAGs, including 57 closed circular genomes, from 23 Danish full-scale wastewater treatment plants. The MAGs account for ~30% of the community based on relative abundance, and meet the stringent MIMAG high-quality draft requirements including full-length rRNA genes. We use the information provided by these MAGs in combination with >13 years of 16S rRNA amplicon sequencing data, as well as Raman microspectroscopy and fluorescence in situ hybridisation, to uncover abundant undescribed lineages belonging to important functional groups.
90% yield production of polymer nano-memristor for in-memory computing
Authors: Zhang Bin , Chen Weilin , Zeng Jianmin , Fan Fei , Gu Junwei , Chen Xinhui , Yan Lin , Xie Guangjun , Liu Shuzhi , Yan Qing , Baik Seung Jae , Zhang Zhi-Guo , Chen Weihua , Hou Jie , El-Khouly Mohamed E. , Zhang Zhang , Liu Gang , Chen Yu
Published: March 2021

Polymer memristors with light weight and mechanical flexibility are preeminent candidates for low-power edge computing paradigms. However, the structural inhomogeneity of most polymers usually leads to random resistive switching characteristics, which lowers the production yield and reliability of nanoscale devices. In this contribution, we report that by adopting the two-dimensional conjugation strategy, a record high 90% production yield of polymer memristors has been achieved with miniaturization and low power potentials. By constructing coplanar macromolecules with 2D conjugated thiophene derivatives to enhance the π–π stacking and crystallinity of the thin film, homogeneous switching takes place across the entire polymer layer, with fast responses in 32 ns, D2D variation down to 3.16% ~ 8.29%, production yield approaching 90%, and scalability into 100 nm scale with tiny power consumption of ~ 10−15 J/bit. The polymer memristor array is capable of acting as both the arithmetic-logic element and multiply-accumulate accelerator for neuromorphic computing tasks.
Mechanism of NanR gene repression and allosteric induction of bacterial sialic acid metabolism
Authors: Horne Christopher R. , Venugopal Hariprasad , Panjikar Santosh , Wood David M. , Henrickson Amy , Brookes Emre , North Rachel A. , Murphy James M. , Friemann Rosmarie , Griffin Michael D. W. , Ramm Georg , Demeler Borries , Dobson Renwick C. J.
Published: March 2021

Bacteria respond to environmental changes by inducing transcription of some genes and repressing others. Sialic acids, which coat human cell surfaces, are a nutrient source for pathogenic and commensal bacteria. TheEscherichia coliGntR-type transcriptional repressor, NanR, regulates sialic acid metabolism, but the mechanism is unclear. Here, we demonstrate that three NanR dimers bind a (GGTATA)3-repeat operator cooperatively and with high affinity. Single-particle cryo-electron microscopy structures reveal the DNA-binding domain is reorganized to engage DNA, while three dimers assemble in close proximity across the (GGTATA)3-repeat operator. Such an interaction allows cooperative protein-protein interactions between NanR dimers via their N-terminal extensions. The effector,N-acetylneuraminate, binds NanR and attenuates the NanR-DNA interaction. The crystal structure of NanR in complex withN-acetylneuraminate reveals a domain rearrangement uponN-acetylneuraminate binding to lock NanR in a conformation that weakens DNA binding. Our data provide a molecular basis for the regulation of bacterial sialic acid metabolism.
Inactivating histone deacetylase HDA promotes longevity by mobilizing trehalose metabolism
Authors: Yu Ruofan , Cao Xiaohua , Sun Luyang , Zhu Jun-yi , Wasko Brian M , Liu Wei , Crutcher Emeline , Liu Haiying , Jo Myeong Chan , Qin Lidong , Kaeberlein Matt , Han Zhe , Dang Weiwei
Published: March 2021

Histone acetylations are important epigenetic markers for transcriptional activation in response to metabolic changes and various stresses. Using the high-throughput SEquencing-Based Yeast replicative Lifespan screen method and the yeast knockout collection, we demonstrate that the HDA complex, a class-II histone deacetylase (HDAC), regulates aging through its target of acetylated H3K18 at storage carbohydrate genes. We find that, in addition to longer lifespan, disruption of HDA results in resistance to DNA damage and osmotic stresses. We show that these effects are due to increased promoter H3K18 acetylation and transcriptional activation in the trehalose metabolic pathway in the absence of HDA. Furthermore, we determine that the longevity effect of HDA is independent of the Cyc8-Tup1 repressor complex known to interact with HDA and coordinate transcriptional repression. Silencing the HDA homologs in C. elegans and Drosophila increases their lifespan and delays aging-associated physical declines in adult flies. Hence, we demonstrate that this HDAC controls an evolutionarily conserved longevity pathway.
Two-timescale response of a large Antarctic ice shelf to climate change
Authors: Naughten Kaitlin A. , De Rydt Jan , Rosier Sebastian H. R. , Jenkins Adrian , Holland Paul R. , Ridley Jeff K.
Published: March 2021

A potentially irreversible threshold in Antarctic ice shelf melting would be crossed if the ocean cavity beneath the large Filchner–Ronne Ice Shelf were to become flooded with warm water from the deep ocean. Previous studies have identified this possibility, but there is great uncertainty as to how easily it could occur. Here, we show, using a coupled ice sheet-ocean model forced by climate change scenarios, that any increase in ice shelf melting is likely to be preceded by an extended period of reduced melting. Climate change weakens the circulation beneath the ice shelf, leading to colder water and reduced melting. Warm water begins to intrude into the cavity when global mean surface temperatures rise by approximately 7 °C above pre-industrial, which is unlikely to occur this century. However, this result should not be considered evidence that the region is unconditionally stable. Unless global temperatures plateau, increased melting will eventually prevail.
Heuristic machinery for thermodynamic studies of SU(N) fermions with neural networks
Authors: Zhao Entong , Lee Jeongwon , He Chengdong , Ren Zejian , Hajiyev Elnur , Liu Junwei , Jo Gyu-Boong
Published: March 2021

The power of machine learning (ML) provides the possibility of analyzing experimental measurements with a high sensitivity. However, it still remains challenging to probe the subtle effects directly related to physical observables and to understand physics behind from ordinary experimental data using ML. Here, we introduce a heuristic machinery by using machine learning analysis. We use our machinery to guide the thermodynamic studies in the density profile of ultracold fermions interacting within SU(N) spin symmetry prepared in a quantum simulator. Although such spin symmetry should manifest itself in a many-body wavefunction, it is elusive how the momentum distribution of fermions, the most ordinary measurement, reveals the effect of spin symmetry. Using a fully trained convolutional neural network (NN) with a remarkably high accuracy of ~94% for detection of the spin multiplicity, we investigate how the accuracy depends on various less-pronounced effects with filtered experimental images. Guided by our machinery, we directly measure a thermodynamic compressibility from density fluctuations within the single image. Our machine learning framework shows a potential to validate theoretical descriptions of SU(N) Fermi liquids, and to identify less-pronounced effects even for highly complex quantum matter with minimal prior understanding.
Long-range optofluidic control with plasmon heating
Authors: Ciraulo B. , Garcia-Guirado J. , de Miguel I. , Ortega Arroyo J. , Quidant R.
Published: March 2021

Using light to manipulate fluids has been a long-sought-after goal for lab-on-a-chip applications to address the size mismatch between bulky external fluid controllers and microfluidic devices. Yet, this goal has remained elusive due to the complexity of thermally driven fluid dynamic phenomena, and the lack of approaches that allow comprehensive multiscale and multiparameter studies. Here, we report an innovative optofluidic platform that fulfills this need by combining digital holographic microscopy with state-of-the-art thermoplasmonics, allowing us to identify the different contributions from thermophoresis, thermo-osmosis, convection, and radiation pressure. In our experiments, we demonstrate that a local thermal perturbation at the microscale can lead to mm-scale changes in both the particle and fluid dynamics, thus achieving long-range transport. Furthermore, thanks to a comprehensive parameter study involving sample geometry, temperature increase, light fluence, and size of the heat source, we showcase an integrated and reconfigurable all-optical control strategy for microfluidic devices, thereby opening new frontiers in fluid actuation technology.
A designer FG-Nup that reconstitutes the selective transport barrier of the nuclear pore complex
Authors: Fragasso Alessio , de Vries Hendrik W. , Andersson John , van der Sluis Eli O. , van der Giessen Erik , Dahlin Andreas , Onck Patrick R. , Dekker Cees
Published: March 2021

Nuclear Pore Complexes (NPCs) regulate bidirectional transport between the nucleus and the cytoplasm. Intrinsically disordered FG-Nups line the NPC lumen and form a selective barrier, where transport of most proteins is inhibited whereas specific transporter proteins freely pass. The mechanism underlying selective transport through the NPC is still debated. Here, we reconstitute the selective behaviour of the NPC bottom-up by introducing a rationally designed artificial FG-Nup that mimics natural Nups. Using QCM-D, we measure selective binding of the artificial FG-Nup brushes to the transport receptor Kap95 over cytosolic proteins such as BSA. Solid-state nanopores with the artificial FG-Nups lining their inner walls support fast translocation of Kap95 while blocking BSA, thus demonstrating selectivity. Coarse-grained molecular dynamics simulations highlight the formation of a selective meshwork with densities comparable to native NPCs. Our findings show that simple design rules can recapitulate the selective behaviour of native FG-Nups and demonstrate that no specific spacer sequence nor a spatial segregation of different FG-motif types are needed to create selective NPCs.
A continuum of invariant sensory and behavioral-context perceptual coding in secondary somatosensory cortex
Authors: Rossi-Pool Román , Zainos Antonio , Alvarez Manuel , Diaz-deLeon Gabriel , Romo Ranulfo
Published: March 2021

A crucial role of cortical networks is the conversion of sensory inputs into perception. In the cortical somatosensory network, neurons of the primary somatosensory cortex (S1) show invariant sensory responses, while frontal lobe neuronal activity correlates with the animal’s perceptual behavior. Here, we report that in the secondary somatosensory cortex (S2), neurons with invariant sensory responses coexist with neurons whose responses correlate with perceptual behavior. Importantly, the vast majority of the neurons fall along a continuum of combined sensory and categorical dynamics. Furthermore, during a non-demanding control task, the sensory responses remain unaltered while the sensory information exhibits an increase. However, perceptual responses and the associated categorical information decrease, implicating a task context-dependent processing mechanism. Conclusively, S2 neurons exhibit intriguing dynamics that are intermediate between those of S1 and frontal lobe. Our results contribute relevant evidence about the role that S2 plays in the conversion of touch into perception.
Emitting long-distance spiral airborne sound using low-profile planar acoustic antenna
Authors: Gao Shuxiang , Li Yunbo , Ma Chengrong , Cheng Ying , Liu Xiaojun
Published: March 2021

Recent years have witnessed a rapidly growing interest in exploring the use of spiral sound carrying artificial orbital angular momentum (OAM), toward establishing a spiral-wave-based technology that is significantly more efficient in energy or information delivering than the ordinary plane wave technology. A major bottleneck of advancing this technology is the efficient excitation of far-field spiral waves in free space, which is a must in exploring the use of spiral waves for long-distance information transmission and particle manipulation. Here, we report a low-profile planar acoustic antenna to modulate wavefronts emitted from a near-field point source and achieve far-field spiral airborne sound carrying OAM. Using the holographic interferogram as a 2D modulated artificial acoustic impedance metasurface, we show the efficient conversion from the surface wave into the propagating spiral shape beam both numerically and experimentally. The vortex fields with spiral phases originate from the complex inter-modal interactions between cylindrical surface waves and a spatially-modulated impedance boundary condition. This antenna can open new routes to highly integrated spiral sound emitters that are critical for practical acoustic functional devices.
RETRACTED ARTICLE: Safety and efficacy of favipiravir versus hydroxychloroquine in management of COVID-19: A randomised controlled trial
Authors: Dabbous Hany M. , El-Sayed Manal H. , El Assal Gihan , Elghazaly Hesham , Ebeid Fatma F. S. , Sherief Ahmed F. , Elgaafary Maha , Fawzy Ehab , Hassany Sahar M. , Riad Ahmed R. , TagelDin Mohamed A.
Published: March 2021

Favipiravir is considered a potential treatment for COVID-19 due its efficacy against different viral infections. We aimed to explore the safety and efficacy of favipiravir in treatment of COVID-19 mild and moderate cases. It was randomized-controlled open-label interventional phase 3 clinical trial [NCT04349241]. 100 patients were recruited from 18th April till 18th May. 50 patients received favipiravir 3200 mg at day 1 followed by 600 mg twice (day 2–day 10). 50 patients received hydroxychloroquine 800 mg at day 1 followed by 200 mg twice (day 2–10) and oral oseltamivir 75 mg/12 h/day for 10 days. Patients were enrolled from Ain Shams University Hospital and Assiut University Hospital. Both arms were comparable as regards demographic characteristics and comorbidities. The average onset of SARS-CoV-2 PCR negativity was 8.1 and 8.3 days in HCQ-arm and favipiravir-arm respectively. 55.1% of those on HCQ-arm turned PCR negative at/or before 7th day from diagnosis compared to 48% in favipiravir-arm (p = 0.7). 4 patients in FVP arm developed transient transaminitis on the other hand heartburn and nausea were reported in about 20 patients in HCQ-arm. Only one patient in HCQ-arm died after developing acute myocarditis resulted in acute heart failure. Favipiravir is a safe effective alternative for hydroxychloroquine in mild or moderate COVID-19 infected patients.
Colonisation of the colonic mucus gel layer with butyrogenic and hydrogenotropic bacteria in health and ulcerative colitis
Authors: Earley Helen , Lennon Grainne , Coffey J. Calvin , Winter Desmond C. , O’Connell P. Ronan
Published: March 2021

Butyrate is the primary energy source for colonocytes and is essential for mucosal integrity and repair. Butyrate deficiency as a result of colonic dysbiosis is a putative factor in ulcerative colitis (UC). Commensal microbes are butyrogenic, while others may inhibit butyrate, through hydrogenotropic activity. The aim of this study was to quantify butyrogenic and hydrogenotropic species and determine their relationship with inflammation within the colonic mucus gel layer (MGL). Mucosal brushings were obtained from 20 healthy controls (HC), 20 patients with active colitis (AC) and 14 with quiescent colitis (QUC). Abundance of each species was determined by RT-PCR. Inflammatory scores were available for each patient. Statistical analyses were performed using Mann–Whitney-U and Kruskall-Wallis tests. ButyrogenicR. hominiswas more abundant in health than UC (p < 0.005), prior to normalisation against total bacteria. HydrogenotropicB. wadsworthiawas reduced in AC compared to HC and QUC (p < 0.005). An inverse correlation existed between inflammation andR. hominis(ρ − 0.460,p < 0.005) andB. wadsworthia(ρ − 0.646,p < 0.005). Other hydrogenotropic species did not widely colonise the MGL. These data support a role for butyrogenic bacteria in UC. Butyrate deficiency in UC may be related to reduced microbial production, rather than inhibition by microbial by-products.
A quantum annealing approach to ionic diffusion in solids
Authors: Utimula Keishu , Ichibha Tom , Prayogo Genki I. , Hongo Kenta , Nakano Kousuke , Maezono Ryo
Published: March 2021

We have developed a framework for using quantum annealing computation to evaluate a key quantity in ionic diffusion in solids, the correlation factor. Existing methods can only calculate the correlation factor analytically in the case of physically unrealistic models, making it difficult to relate microstructural information about diffusion path networks obtainable by current ab initio techniques to macroscopic quantities such as diffusion coefficients. We have mapped the problem into a quantum spin system described by the Ising Hamiltonian. By applying our framework in combination with ab initio technique, it is possible to understand how diffusion coefficients are controlled by temperatures, pressures, atomic substitutions, and other factors. We have calculated the correlation factor in a simple case with a known exact result by a variety of computational methods, including simulated quantum annealing on the spin models, the classical random walk, the matrix description, and quantum annealing on D-Wave with hybrid solver . This comparison shows that all the evaluations give consistent results with each other, but that many of the conventional approaches require infeasible computational costs. Quantum annealing is also currently infeasible because of the cost and scarcity of qubits, but we argue that when technological advances alter this situation, quantum annealing will easily outperform all existing methods.
Urban storm water infiltration systems are not reliable sinks for biocides: evidence from column experiments
Authors: Bork Marcus , Lange Jens , Graf-Rosenfellner Markus , Hensen Birte , Olsson Oliver , Hartung Thomas , Fernández-Pascual Elena , Lang Friederike
Published: March 2021

Groundwater quality in urban catchments is endangered by the input of biocides, such as those used in facade paints to suppress algae and fungal growth and washed off by heavy rainfall. Their retention in storm water infiltration systems (SIS) depends, in addition to their molecular properties, on chemical properties and structure of the integrated soil layer. These soil properties change over time and thus possibly also the relevance of preferential flow paths, e.g. due to ongoing biological activity. To investigate the mobility of biocides in SIS, we analyzed the breakthrough of differently adsorbing tracers (bromide, uranine, sulforhodamine B) and commonly used biocides (diuron, terbutryn, octhilinone) in laboratory column experiments of undisturbed soil cores of SIS, covering ages from 3 to 18 years. Despite similar soil texture and chemical soil properties, retention of tracers and biocides differed distinctly between SIS. Tracer and biocide breakthrough ranged from 54% and 5%, to 96% and 54%, respectively. We related the reduced solute retention to preferential transport in macropores as could be confirmed by brilliant blue staining. Our results suggest an increasing risk of groundwater pollution with increasing number of macropores related to biological activity and the age of SIS.
Paclitaxel loading in cationic liposome vectors is enhanced by replacement of oleoyl with linoleoyl tails with distinct lipid shapes
Authors: Zhen Yuhong , Ewert Kai K. , Fisher William S. , Steffes Victoria M. , Li Youli , Safinya Cyrus R.
Published: March 2021

Lipid carriers of hydrophobic paclitaxel (PTX) are used in clinical trials for cancer chemotherapy. Improving their loading capacity requires enhanced PTX solubilization. We compared the time-dependence of PTX membrane solubility as a function of PTX content in cationic liposomes (CLs) with lipid tails containing one (oleoyl; DOPC/DOTAP) or two (linoleoyl; DLinPC/newly synthesized DLinTAP) cis double bonds by using microscopy to generate kinetic phase diagrams. The DLin lipids displayed significantly increased PTX membrane solubility over DO lipids. Remarkably, 8 mol% PTX in DLinTAP/DLinPC CLs remained soluble for approximately as long as 3 mol% PTX (the solubility limit, which has been the focus of most previous studies and clinical trials) in DOTAP/DOPC CLs. The increase in solubility is likely caused by enhanced molecular affinity between lipid tails and PTX, rather than by the transition in membrane structure from bilayers to inverse cylindrical micelles observed with small-angle X-ray scattering. Importantly, the efficacy of PTX-loaded CLs against prostate cancer cells (their IC50 of PTX cytotoxicity) was unaffected by changing the lipid tails, and toxicity of the CL carrier was negligible. Moreover, efficacy was approximately doubled against melanoma cells for PTX-loaded DLinTAP/DLinPC over DOTAP/DOPC CLs. Our findings demonstrate the potential of chemical modifications of the lipid tails to increase the PTX membrane loading while maintaining (and in some cases even increasing) the efficacy of CLs. The increased PTX solubility will aid the development of liposomal PTX carriers that require significantly less lipid to deliver a given amount of PTX, reducing side effects and costs.
Developmental events and cellular changes occurred during esophageal development of quail embryos
Authors: Soliman Soha A. , Madkour Fatma A.
Published: March 2021

The current study focused on the histogenesis of the esophagus in quail embryos. Formation of the gut tube occurred on the 4th day of incubation. Development of the muscular layers occurred in a sequential manner; the inner circular layer on the 7th day, the outer longitudinal layer on the 8th day and the muscularis mucosae on the 9th day. Glandular development began on the 13th day of incubation. The epithelium was pseudostratified columnar that consisted of mucous cells, dendritic cells, and keratinocyte precursors. Epithelial stratification occurred on the 15th day of incubation. We used Mallory trichrome, Weigert-Van Gieson, and Gomori silver stains to visualize fibrous components. Scanned samples showed formation of endoderm and mesoderm on the 5th day of incubation. A layer of myoblasts developed on the 8th day of incubation. Formation of mucosal folds, which contained glandular openings, occurred on the 14th to 17th days of incubation. On the 5th to 8th days of incubation, CD34 and vascular endothelial growth factor (VEGF) positive-mesodermal cells, and telocytes (TCs) were detected. On the 15th day of incubation, CD34 and VEGF positive-telocytes, and fibroblasts, were identified. The current study described the correlations between functional morphology and evolutionary biology.
Meta-analysis identifies the effect of dietary multi-enzyme supplementation on gut health of pigs
Authors: Ramani Sivasubramanian , Recharla Neeraja , Hwang Okhwa , Jeong Jinyoung , Park Sungkwon
Published: March 2021

Gut health though is not well defined the role of gastrointestinal tract is vital if an animal must perform well. Apart from digestion, secretion, and absorption gut is harbored with consortium of microbiota which plays a key role in one’s health. Enzymes, one of the alternatives for antibiotics with beneficial effects on digestion and consistency of food and its effect on gut health. The effect of enzyme supplementation on gut health is not well established and the objective of this meta-analysis is to investigate if the enzyme supplement has influence on gut. This meta-analysis includes 1221 experiments which has single enzyme studies and or studies with multiple enzyme complexes but not challenged. The ratio of Lactobacillus and E. coli is related to ADFI which showed comparatively lower negative correlation coefficient, with − 0.052 and − 0.035, respectively, whose I2 values are below 25%, showing that these studies show a significantly lower level of heterogeneity. Correlation between villus height, crypt depth, their ratio and fatty acid is also assessed, and it showed that when the animal is supplemented with two enzyme complexes resulted in positive gut health rather than the single or more than two enzymes.