julilili42/papers huggingface dataset:
Un-jamming due to energetic instability: statics to dynamics
2021-08-27

Abstract Jamming/un-jamming, the transition between solid- and fluid-like behavior in granular matter, is an ubiquitous phenomenon in need of a sound understanding. As argued here, in addition to the usual un-jamming by vanishing pressure due to a decrease of density, there is also yield (plastic rearrangements and un-jamming that occur) if, e.g., for given pressure, the shear stress becomes too large. Similar to the van der Waals transition between vapor and water, or the critical current in superconductors, we believe that one mechanism causing yield is by the loss of the energy’s convexity (causing irreversible re-arrangements of the micro-structure, either locally or globally). We focus on this mechanism in the context of granular solid hydrodynamics (GSH), generalized for very soft materials, i.e., large elastic deformations, employing it in an over-simplified (bottom-up) fashion by setting as many parameters as possible to constant. Also, we complemented/completed GSH by using various insights/observations from particle simulations and calibrating some of the theoretical parameters—both continuum and particle points of view are reviewed in the context of the research developments during the last few years. Any other energy-based elastic-plastic theory that is properly calibrated (top-down), by experimental or numerical data, would describe granular solids. But only if it would cover granular gas, fluid, and solid states simultaneously (as GSH does) could it follow the system transitions and evolution through all states into un-jammed, possibly dynamic/collisional states—and back to elastically stable ones. We show how the un-jamming dynamics starts off, unfolds, develops, and ends. We follow the system through various deformation modes: transitions, yielding, un-jamming and jamming, both analytically and numerically and bring together the material point continuum model with particle simulations, quantitatively. Graphic abstract
Audio Retrieval with Natural Language Queries
2021-08-27

We consider the task of retrieving audio using free-form natural language queries. To study this problem, which has received limited attention in the existing literature, we introduce challenging new benchmarks for text-based audio retrieval using text annotations sourced from the Audiocaps and Clotho datasets. We then employ these benchmarks to establish baselines for cross-modal audio retrieval, where we demonstrate the benefits of pre-training on diverse audio tasks. We hope that our benchmarks will inspire further research into cross-modal text-based audio retrieval with free-form text queries.
On center of mass and foliations by constant spacetime mean curvature surfaces for isolated systems in General Relativity
2021-08-27

Abstract We propose a new foliation of asymptotically Euclidean initial data sets by 2-spheres of constant spacetime mean curvature (STCMC). The leaves of the foliation have the STCMC-property regardless of the initial data set in which the foliation is constructed which asserts that there is a plethora of STCMC 2-spheres in a neighborhood of spatial infinity of any asymptotically flat spacetime. The STCMC-foliation can be understood as a equivariant relativistic generalization of the CMC-foliation suggested by Huisken and Yau (Invent Math 124:281–311, 1996). We show that a unique STCMC-foliation exists near infinity of any asymptotically Euclidean initial data set with non-vanishing energy which allows for the definition of a new notion of total center of mass for isolated systems. This STCMC-center of mass transforms equivariantly under the asymptotic Poincaré group of the ambient spacetime and in particular evolves under the Einstein evolution equations like a point particle in Special Relativity. The new definition also remedies subtle deficiencies in the CMC-approach to defining the total center of mass suggested by Huisken and Yau (Invent Math 124:281–311, 1996) which were described by Cederbaum and Nerz (Ann Henri Poincaré 16:1609–1631, 2015).
Expression and subcellular localization of USH1C/harmonin in the human retina provide insights into pathomechanisms and therapy
2021-08-27

Abstract Usher syndrome (USH) is the most common form of hereditary deafness-blindness in humans. USH is a complex genetic disorder, assigned to three clinical subtypes differing in onset, course, and severity, with USH1 being the most severe. Rodent USH1 models do not reflect the ocular phenotype observed in human patients to date; hence, little is known about the pathophysiology of USH1 in the human eye. One of the USH1 genes, USH1C , exhibits extensive alternative splicing and encodes numerous harmonin protein isoforms that function as scaffolds for organizing the USH interactome. RNA-seq analysis of human retinas uncovered harmonin_a1 as the most abundant transcript of USH1C . Bulk RNA-seq analysis and immunoblotting showed abundant expression of harmonin in Müller glia cells (MGCs) and retinal neurons. Furthermore, harmonin was localized in the terminal endfeet and apical microvilli of MGCs, presynaptic region (pedicle) of cones, and outer segments of rods as well as at adhesive junctions of MGCs and photoreceptors in the outer limiting membrane (OLM). Our data provide evidence for the interactions of harmonin with OLM molecules in photoreceptors (PRCs) and MGCs and rhodopsin in PRCs. Subcellular expression and colocalization of harmonin correlate with the clinical phenotype observed in USH1C patients. In addition, primary cilia defects in USH1C patient-derived fibroblasts could be reverted by the delivery of harmonin_a1 transcript isoform. Our data provide novel insights into PRC cell biology, USH1C pathophysiology, and for developing gene therapy treatment.
Peripheral Expression Levels of Selected Oxidative Stress-Related Genes in Alzheimer’s Disease
2021-08-27

Amaç: Oksidatif stres, Alzheimer hastalığının (AH) etiyolojisinde önemli bir rol oynamaktadır. Antioksidan enzimler reaktif oksijen türevlerinin (ROS) hücreye zarar vermesini önlemek için çok önemlidir. Oksidan ve antioksidan enzimleri kodlayan genlerin anlatım seviyelerindeki değişimler hücrenin oksidatif strese karşı verdiği yanıtta anahtar faktördür. Bu nedenle çalışmamızda, AH hastalarının periferik kanlarında spesifik oksidatif stres ile ilişkili genlerin (solut taşıyıcı aile 7 üye 11 (SLC7A11), glutatyon peroksidaz 4 (GPX4), katalaz (CAT ) ve açil koA sentetaz uzun zincir aile üyesi 4 (ACSL4)) anlatım düzeylerindeki değişimin araştırılması amaçlanmıştır.Gereç ve Yöntem: Periferik kan lökositlerinde oksidatif stresle ilgili genlerin ekspresyon düzeylerindeki değişiklikler 25 AH hastası ve 22 kontrolde kantitatif ters transkripsiyon polimeraz zincir reaksiyonu (qRT-PCR) ile belirlenmiş ve sonuçlar istatistiksel olarak değerlendirilmiştir.Bulgular:SLC7A11, GPX4, CAT ve ACSL4 genlerinin anlatım düzeyleri, AH hastaları ve kontroller arasında istatistiksel olarak bir farklılık göstermemiştir. Ayrıca, sonuçlarımız başlangıç yaşı ile ACSL4 ekspresyonu arasında anlamlı negatif bir korelasyon olduğunu göstermiştir.Sonuç: Araştırmamız, AH hastalarının periferik kanlarında SLC7A11, GPX4 ve ACSL4 genlerinin anlatım düzeylerini değerlendiren ilk çalışma olup, sonuçlarımız söz konusu genlerin periferik kandaki an-latımlarının AH&#039;de değişmediğini göstermiştir. Bununla birlikte, az sayıda hasta ve kontrol nedeniyle, bu bulgular başlangıç niteliğindedir ve daha geniş çalışma gruplarında doğrulanması gerekmektedir.
Extensive incorporation, polarisation and improved maturation of transplanted human cones in a murine cone degeneration model
2021-08-28

Summary Once human photoreceptors die, they do not regenerate, thus photoreceptor transplantation has emerged as a potential treatment approach for blinding diseases. Improvements in transplant organization, donor cell maturation and synaptic connectivity to the host will be critical in advancing this technology to clinical practice. Unlike the unstructured grafts of prior cell suspension transplantations into end-stage degeneration models, we describe extensive incorporation of iPSC retinal organoid-derived human photoreceptors into mice with cone dysfunction. This incorporative phenotype was validated in both cone-only as well as pan-photoreceptor transplantations. Rather than forming a glial barrier, Müller cells extend throughout the graft, even forming a common outer limiting membrane. Donor-host interaction appears to promote polarisation as well as development of morphological features critical for light detection, namely formation of inner and well stacked outer segments oriented towards the RPE. Putative synapse formation and graft function is evident both at a structural and electrophysiological level. Overall, these results show that human photoreceptors interact readily with a partially degenerated retina. Moreover, incorporation into the host retina appears to be beneficial to graft maturation, polarisation and function. Highlights Generation of the first human iPSC cone reporter line Human cones extensively incorporate into the retina of mice with cone degeneration Donor cone age and time in vivo are important factors for transplant incorporation Incorporation into the host retina correlates with graft polarisation Improved photoreceptor maturation after transplantation in vivo vs. in vitro Re-establishment of cone-mediated light-responses in the cone deficient mouse
Fluid‐based augmentation of magnetic resonance visualization of interventional devices
2021-08-28

Abstract Purpose To evaluate the transient artifact augmentation of microtubes in magnetic resonance imaging by fluid injection. Methods Twenty‐one fluorinated ethylene propylene catheters (inner diameter 760 μm) were filled with three different contrast media at various concentrations (Ferucarbotran, Resovist®, Bayer Schering Pharma; Manganese dichloride, MnCl2, Sigma‐Aldrich; Gadobutrol, Gadovist®, Bayer Schering Pharma). Artifact appearance was determined in an ex vivo phantom at 1.5 T using three different sequences: T1‐weighted three‐dimensional volume interpolated breath‐hold examination, T2‐weighted turbo spin echo, and T1‐weighted fast low angle shot. Catheter angulation to the main magnetic field (B0) was varied. Influence of parameters on artifact diameters was assessed with a multiple linear regression similar to an analysis of variance. Results Artifact diameter was significantly influenced by the contrast agent ( p &lt; 0.001), concentration of the contrast agent ( p &lt; 0.001), angulation of the phantom to B0 with the largest artifact at 90° ( p &lt; 0.001), and encoding direction with a larger diameter in phase encoding direction (PED, p &lt; 0.001). Mean artifact diameters at 90° angulation to B0 in PED were 18.5 ± 5.4 mm in 0.5 mmol/ml Ferucarbotran, 8.7 ± 2.5 mm in 1 mmol/ml Gadobutrol, and 11.6 ± 4.6 mm in 5 mmol/ml MnCl 2 . Conclusions Fluid‐based contrast agents might be applied to interventional devices and thus temporarily augment the artifact ensuring both visibility and safe navigation.
Automation improves repeatability of retinal oximetry measurements
2021-08-28

Abstract Purpose Retinal oximetry is a technique based on spectrophotometry where images are analyzed with software capable of calculating vessel oxygen saturation and vessel diameter. In this study, the effect of automation of measurements of retinal vessel oxygen saturation and vessel diameter is explored. Methods Until now, operators have had to choose each vessel segment to be measured explicitly. A new, automatic version of the software automatically selects the vessels once the operator defines a measurement area. Five operators analyzed image pairs from the right eye of 23 healthy subjects with semiautomated retinal oximetry analysis software, Oxymap Analyzer (v2.5.1), and an automated version (v3.0). Inter- and intra-operator variability was investigated using the intraclass correlation coefficient (ICC) between oxygen saturation measurements of vessel segments in the same area of the retina. Results For manual saturation measurements, the inter-rater ICC was 0.80 for arterioles and venules. For automated saturation measurements, the inter-rater ICC was 0.97 for arterioles and 0.96 for venules. For manual diameter measurements, the inter-rater ICC was 0.71 for arterioles and venules. For automated diameter measurements the inter-rater ICC was 0.97 for arterioles and 0.95 for venules. The inter-rater ICCs were different ( p &lt; 0.01) between the semiautomated and automated version in all instances. Conclusion Automated measurements of retinal oximetry values are more repeatable compared to measurements where vessels are selected manually.
A Common CDH13 Variant Is Associated with Low Agreeableness and Neural Responses to Working Memory Tasks in ADHD
2021-08-29

The cell—cell signaling gene CDH13 is associated with a wide spectrum of neuropsychiatric disorders, including attention-deficit/hyperactivity disorder (ADHD), autism, and major depression. CDH13 regulates axonal outgrowth and synapse formation, substantiating its relevance for neurodevelopmental processes. Several studies support the influence of CDH13 on personality traits, behavior, and executive functions. However, evidence for functional effects of common gene variation in the CDH13 gene in humans is sparse. Therefore, we tested for association of a functional intronic CDH13 SNP rs2199430 with ADHD in a sample of 998 adult patients and 884 healthy controls. The Big Five personality traits were assessed by the NEO-PI-R questionnaire. Assuming that altered neural correlates of working memory and cognitive response inhibition show genotype-dependent alterations, task performance and electroencephalographic event-related potentials were measured by n-back and continuous performance (Go/NoGo) tasks. The rs2199430 genotype was not associated with adult ADHD on the categorical diagnosis level. However, rs2199430 was significantly associated with agreeableness, with minor G allele homozygotes scoring lower than A allele carriers. Whereas task performance was not affected by genotype, a significant heterosis effect limited to the ADHD group was identified for the n-back task. Heterozygotes (AG) exhibited significantly higher N200 amplitudes during both the 1-back and 2-back condition in the central electrode position Cz. Consequently, the common genetic variation of CDH13 is associated with personality traits and impacts neural processing during working memory tasks. Thus, CDH13 might contribute to symptomatic core dysfunctions of social and cognitive impairment in ADHD.
The Art of Inducing Hypoxia
2021-08-30

Many cells in the human body strongly react on decreased oxygen concentrations, generally defined as hypoxia. Therefore, inducing hypoxia in vitro is essential for research. Classically, hypoxia is induced using a hypoxia chamber, but alternative methods exist that do not require special equipment. Here, we compared three different methods to induce hypoxia without a hypoxia chamber: the chemical stabilization of HIF-1α by CoCl2, the decrease in pericellular oxygen concentrations by increased media height, and the consumption of oxygen by an enzymatic system. Hypoxia induction was further analyzed within three different cell culture systems: 2D (adherent) osteoprogenitor cells, monocytic (suspension) cells, and in a 3D in vitro fracture hematoma model. The different methods were analyzed within the scope of fracture healing regarding inflammation and differentiation. We could show that all three induction methods were feasible for hypoxia induction within adherent cells. Increased media heights did not stimulate a hypoxic response within suspension cells and in the 3D system. Chemical stabilization of HIF-1α showed limitations when looking at the expression of cytokines in osteoprogenitors and monocytes. Enzymatic reduction of oxygen proofed to be most effective within all three systems inducing inflammation and differentiation.
Area-Wide Prediction of Vertebrate and Invertebrate Hole Density and Depth across a Climate Gradient in Chile Based on UAV and Machine Learning
2021-08-30

Burrowing animals are important ecosystem engineers affecting soil properties, as their burrowing activity leads to the redistribution of nutrients and soil carbon sequestration. The magnitude of these effects depends on the spatial density and depth of such burrows, but a method to derive this type of spatially explicit data is still lacking. In this study, we test the potential of using consumer-oriented UAV RGB imagery to determine the density and depth of holes created by burrowing animals at four study sites along a climate gradient in Chile, by combining UAV data with empirical field plot observations and machine learning techniques. To enhance the limited spectral information in RGB imagery, we derived spatial layers representing vegetation type and height and used landscape textures and diversity to predict hole parameters. Across-site models for hole density generally performed better than those for depth, where the best-performing model was for the invertebrate hole density (R2 = 0.62). The best models at individual study sites were obtained for hole density in the arid climate zone (R2 = 0.75 and 0.68 for invertebrates and vertebrates, respectively). Hole depth models only showed good to fair performance. Regarding predictor importance, the models heavily relied on vegetation height, texture metrics, and diversity indices.
Search for Dark Matter Annihilation Signals from Unidentified Fermi-LAT Objects with H.E.S.S.
2021-08-30

Abstract Cosmological N -body simulations show that Milky Way–sized galaxies harbor a population of unmerged dark matter (DM) subhalos. These subhalos could shine in gamma-rays and eventually be detected in gamma-ray surveys as unidentified sources. We performed a thorough selection among unidentified Fermi-Large Area Telescope Objects (UFOs) to identify them as possible tera-electron-volt-scale DM subhalo candidates. We search for very-high-energy (E ≳ 100 GeV) gamma-ray emissions using H.E.S.S. observations toward four selected UFOs. Since no significant very-high-energy gamma-ray emission is detected in any data set of the four observed UFOs or in the combined UFO data set, strong constraints are derived on the product of the velocity-weighted annihilation cross section 〈 σ v 〉 by the J factor for the DM models. The 95% confidence level observed upper limits derived from combined H.E.S.S. observations reach 〈 σ v 〉 J values of 3.7 × 10 −5 and 8.1 × 10 −6 GeV 2 cm −2 s −1 in the W + W − and τ + τ − channels, respectively, for a 1 TeV DM mass. Focusing on thermal weakly interacting massive particles, the H.E.S.S. constraints restrict the J factors to lie in the range 6.1 × 10 19 –2.0 × 10 21 GeV 2 cm −5 and the masses to lie between 0.2 and 6 TeV in the W + W − channel. For the τ + τ − channel, the J factors lie in the range 7.0 × 10 19 –7.1 × 10 20 GeV 2 cm −5 and the masses lie between 0.2 and 0.5 TeV. Assuming model-dependent predictions from cosmological N -body simulations on the J -factor distribution for Milky Way–sized galaxies, the DM models with masses &gt;0.3 TeV for the UFO emissions can be ruled out at high confidence level.
Nanobodies as allosteric modulators of Parkinson’s disease-associated LRRK2
2021-08-30

Abstract Mutations in the gene coding for Leucine-Rich Repeat Kinase 2 (LRRK2) are a leading cause of the inherited form of Parkinson’s disease (PD), while LRRK2 overactivation is also associated with the more common idiopathic form of PD. LRRK2 is a large multi-domain protein, including a GTPase as well as a Ser/Thr protein kinase domain. Common disease-causing mutations increase LRRK2 kinase activity, presenting LRRK2 as an attractive target for inhibitory drug design. Currently, drug development has mainly focused on ATP-competitive kinase inhibitors. Here, we report the identification and characterization of a variety of Nanobodies that bind to different LRRK2 domains and inhibit or activate LRRK2 activity in cells and in vitro. Importantly, diverse groups of Nanobodies were identified that inhibit LRRK2 kinase activity through a mechanism that does not involve binding to the ATP pocket or even to the kinase domain. Moreover, while certain Nanobodies completely inhibit the LRRK2 kinase activity, we also identified Nanobodies that specifically inhibit the phosphorylation of Rab protein substrates. Finally, in contrast to current type-I kinase inhibitors, the studied kinase-inhibitory Nanobodies did not induce LRRK2 microtubule association. These comprehensively characterized Nanobodies represent versatile tools to study the LRRK2 function and mechanism, and can pave the way toward novel diagnostic and therapeutic strategies for PD.
COVID-19 mitigation strategies for reduced transmission in U.S. prisons
2021-08-30

During the global COVID-19 pandemic, prisons have been the center of numerous outbreaks. Current efforts in virus containment have largely failed, due to a lack of standardized guidelines and reporting of key data regarding testing, cases, and deaths within state prisons. This article addresses challenges associated with pandemic management in prisons and policy options to reduce risk to inmates, prison staff, and the communities surrounding prisons. A comprehensive framework for evaluating a state prison’s virus management can facilitate improved responses, in particular amongst the rise of more virulent strains and ongoing cases. Such a framework may also serve as guidance in other situations of a similar nature.
The True Superheroes: Microorganisms Survive it All!
2021-08-30

Did you know that microorganisms can live far up in the clouds and deep in the Earth’s crust? These tiny organisms have adapted to all special habitats on Earth. To study special habitats, scientists can focus on the microorganisms and their biological reactions, or on the non-living components, like minerals and chemical reactions. However, it can be difficult to separate the two! Since little was known about the best way to remove microorganisms from environmental samples without changing the non-living properties of the sample, we decided to perform an experiment to find out. We exposed marine sediments to three different methods of sterilization, to see which method was best for eliminating microorganisms. We also studied whether the three methods affected the chemical properties of our samples. We found that it is challenging to create sterile conditions because some microorganisms can survive high pressure, high temperature, radiation, and toxic chemicals!