Miracle-dz/UniFAR-FTUs huggingface dataset:
Identification of QS-21 as an Inflammasome-activating Molecular Component of Saponin Adjuvants*

Many immunostimulants act as vaccine adjuvants via activation of the innate immune system, although in many cases it is unclear which specific molecules contribute to the stimulatory activity. QS-21 is a defined, highly purified, and soluble saponin adjuvant currently used in licensed and exploratory vaccines, including vaccines against malaria, cancer, and HIV-1. However, little is known about the mechanisms of cellular activation induced by QS-21. We observed QS-21 to elicit caspase-1-dependent IL-1β and IL-18 release in antigen-presenting cells such as macrophages and dendritic cells when co-stimulated with the TLR4-agonist adjuvant monophosphoryl lipid A. Furthermore, our data suggest that the ASC-NLRP3 inflammasome is responsible for QS-21-induced IL-1β/IL-18 release. At higher concentrations, QS-21 induced macrophage and dendritic cell death in a caspase-1-, ASC-, and NLRP3-independent manner, whereas the presence of cholesterol rescued cell viability. A nanoparticulate adjuvant that contains QS-21 as part of a heterogeneous mixture of saponins also induced IL-1β in an NLRP3-dependent manner. Interestingly, despite the role NLRP3 plays for cellular activation in vitro, NLRP3-deficient mice immunized with HIV-1 gp120 and QS-21 showed significantly higher levels of Th1 and Th2 antigen-specific T cell responses and increased IgG1 and IgG2c compared with wild type controls. Thus, we have identified QS-21 as a nonparticulate single molecular saponin that activates the NLRP3 inflammasome, but this signaling pathway may contribute to decreased antigen-specific responses in vivo.
Retinal Waves Are Governed by Collective Network Properties

Propagating neural activity in the developing mammalian retina is required for the normal patterning of retinothalamic connections. This activity exhibits a complex spatiotemporal pattern of initiation, propagation, and termination. Here, we discuss the behavior of a model of the developing retina using a combination of simulation and analytic calculation. Our model produces spatially and temporally restricted waves without requiring inhibition, consistent with the early depolarizing action of neurotransmitters in the retina. We find that highly correlated, temporally regular, and spatially restricted activity occurs over a range of network parameters; this ensures that such spatiotemporal patterns can be produced robustly by immature neural networks in which synaptic transmission by individual neurons may be unreliable. Wider variation of these parameters, however, results in several different regimes of wave behavior. We also present evidence that wave properties are locally determined by a single variable, the fraction of recruitable (i.e., nonrefractory) cells within the dendritic field of a retinal neuron. From this perspective, a given local area’s ability to support waves with a wide range of propagation velocities—as observed in experiment—reflects the variability in the local state of excitability of that area. This prediction is supported by whole-cell voltage-clamp recordings, which measure significant wave-to-wave variability in the amount of synaptic input a cell receives when it participates in a wave. This approach to describing the developing retina provides unique insight into how the organization of a neural circuit can lead to the generation of complex correlated activity patterns.
Materials for Magnetic Recording Applications

In the first part of this work, the influence of hydrogen on the structural and magnetic properties of Fe/V(001) superlattices was studied. The local structure of the vanadium-hydride layers was determined by extended x-ray absorption fine structure (EXAFS) measurements. The magnetic ordering in a weakly coupled Fe/V(001) superlattice was investigated using the magneto-optical Kerr effect (MOKE). The interlayer exchange coupling is weakened upon alloying with hydrogen and a phase with short-range magnetic order was observed.The second part is concerned with first-principles calculations of magnetic materials, with a focus on magnetic recording applications. The uniaxial magnetic anisotropy energy (MAE) of Fe, Co, and Ni was calculated for tetragonal and trigonal structures. Based on an analysis of the electronic states of tetragonal Fe and Co at the center of the Brillouin zone, tetragonal Fe-Co alloys were proposed as a material that combines a large uniaxial MAE with a large saturation magnetization. This was confirmed by experimental studies on (Fe,Co)/Pt superlattices. The large uniaxial MAE of L10 FePt is caused by the large spin-orbit interaction on the Pt sites in connection with a strong hybridization between Fe and Pt. Furthermore, it was shown that the uniaxial MAE can be increased by alloying the Fe sublattice with Mn. The combination of the high-moment rare-earth (RE) metals with the high-TC 3d transition metals in RE/Cr/Fe multilayers (RE = Gd, Tb, Dy) gives rise to a strong ferromagnetic effective exchange interaction between the Fe layers and the RE layer. The MAE of hcp Gd was found to have two principal contributions, namely the dipole interaction of the large localized 4f spins and the band electron magnetic anisotropy due to the spin-orbit interaction. The peculiar temperature dependence of the easy axis of magnetization was reproduced on a qualitative level.
The Beating of Chemical Pulps – The Action and the Effects

The article reviews the state of knowledge of the action and effect of beating on chemical pulps. The view is put forward that the problem is so complex that researchers have been tempted to oversimplify it, but some of these simplifications now may represent a barrier to progress. New approaches incorporating newly developed research techniques are proposed for future research efforts.
Anti-Inflammatory Mechanisms in the Vascular Wall

Abstract— The role of vascular cells during inflammation is critical and is of particular importance in inflammatory diseases, including atherosclerosis, ischemia/reperfusion, and septic shock. Research in vascular biology has progressed remarkably in the last decade, resulting in a better understanding of the vascular cell responses to inflammatory stimuli. Most of the vascular inflammatory responses are mediated through the I&kgr;B/nuclear factor-&kgr;B system. Much recent work shows that vascular inflammation can be limited by anti-inflammatory counteregulatory mechanisms that maintain the integrity and homeostasis of the vascular wall. The anti-inflammatory mechanisms in the vascular wall involve anti-inflammatory external signals and intracellular mediators. The anti-inflammatory external signals include the anti-inflammatory cytokines, transforming growth factor-&bgr;, interleukin-10 and interleukin-1 receptor antagonist, HDL, as well as some angiogenic and growth factors. Physiological laminar shear stress is of particular importance in protecting endothelial cells against inflammatory activation. Its effects are partly mediated through NO production. Finally, endogenous cytoprotective genes or nuclear receptors, such as the peroxisome proliferator–activated receptors, can be expressed by vascular cells in response to proinflammatory stimuli to limit the inflammatory process and the injury.
Tracking the Evolution and Diversity in Network Usage of Smartphones

We analyze the evolution of smartphone usage from a dataset obtained from three, 15-day-long, user-side, measurements with over 1500 recruited smartphone users in the Greater Tokyo area from 2013 to 2015. This dataset shows users across a diverse range of networks; cellular access (3G to LTE), WiFi access (2.4 to 5GHz), deployment of more public WiFi access points (APs), as they use diverse applications such as video, file synchronization, and major software updates. Our analysis shows that smartphone users select appropriate network interfaces taking into account the deployment of emerging technologies, their bandwidth demand, and their economic constraints. Thus, users show diversity in both how much traffic they send, as well as on what networks they send it. We show that users are gradually but steadily adopting WiFi at home, in offices, and public spaces over these three years. The majority of light users have been shifting their traffic to WiFi. Heavy hitters acquire more bandwidth via WiFi, especially at home. The percentage of users explicitly turning off their WiFi interface during the day decreases from 50% to 40%. Our results highlight that the offloading environment has been improved during the three years, with more than 40% of WiFi users connecting to multiple WiFi APs in one day. WiFi offload at offices is still limited in our dataset due to a few accessible APs, but WiFi APs in public spaces have been an alternative to cellular access for users who request not only simple connectivity but also bandwidth-consuming applications such as video streaming and software updates.
Flashing light signaling circuit in sponges: Endogenous light generation after tissue ablation in Suberites domuncula

The skeleton of siliceous sponges (phylum Porifera: classes Demospongiae and Hexactinellida), composed of tightly interacting spicules that assemble to a genetically fixed scaffold, is formed of bio‐silica. This inorganic framework with the quality of quartz glass has been shown to operate as light waveguide in vitro and very likely has a similar function in vivo. Furthermore, the molecular toolkit for endogenous light generation (luciferase) and light/photon harvesting (cryptochrome) has been identified in the demosponge Suberites domuncula. These three components of a light signaling system, spicules—luciferase—cryptochrome, are concentrated in the surface layers (cortex) of the poriferan body. Specimens from which this cortex has been removed/ablated do not emit light. However, with regeneration and reconstitution of the cortex the animals re‐gain the capacity to flash light. This newly discovered characteristic of sponges to generate light prompted us to investigate the genetic basis for the endogenous light signaling system. As a potential transcription factor involved in the expression of luciferase and cryptochrome, a SOX‐related protein has been identified. In dark‐adapted animals or in tissue from below the cortex region, the medulla, no gene or protein expression of SOX‐related protein, luciferase, and cryptochrome could be detected. However, during the regeneration of the cortex, a stage‐specific expression pattern was recorded: SOX‐related protein > luciferase > cryptochrome. We conclude that a flashing light signaling circuit exists, which might control the retinoic acid‐induced differentiation of stem cells into pulsating and contracting sponge cells, that is, pinacocytes and myocytes. J. Cell. Biochem. 111: 1377–1389, 2010. © 2010 Wiley‐Liss, Inc.
Varying Benefits of Irrigation Expansion for Crop Production Under a Changing Climate and Competitive Water Use Among Crops

Replacing rainfed cropping systems with irrigated systems has been deemed an effective agricultural adaptation measure in response to climate change. However, few agricultural impact assessments have considered changes in the water availability because of climate change and water use competition among crops. Here we assessed future global crop production under a changing climate and expanded surface water irrigation using the large‐scale crop‐river coupled model CROVER. The future irrigated area was estimated by extrapolating from the historical linear trends. We present three interesting cases from this global analysis. The results under a high‐emission scenario (Representative Concentration Pathway 8.5) showed that, in response to irrigation expansion, maize production in Europe will increase, whereas rice production in East Asia will not increase because of competitive water use between rice and other crops. Furthermore, we found that future precipitation over crop‐producing areas in the Indus River watershed will decrease but that increased precipitation in the higher mountainous areas of the watershed will compensate for these diminished water resources, thereby reducing drought damage. Our findings reveal that competitive water use among crops and the geographical patterns of future changes in precipitation influence the benefits of expanding irrigation for crop production under a changing climate.
Ada-NAV: Adaptive Trajectory-Based Sample Efficient Policy Learning for Robotic Navigation

: Reinforcement learning methods, while effective for learning robotic navigation strategies, are known to be highly sample inefficient. This sample inefficiency comes in part from not suitably balancing the explore-exploit dilemma, especially in the presence of non-stationarity, during policy optimization. To incorporate a balance of exploration-exploitation for sample efficiency, we propose Ada-NAV, an adaptive trajectory length scheme where the length grows as a policy’s randomness, represented by its Shannon or differential entropy, decreases. Our adaptive trajectory length scheme emphasizes exploration at the beginning of training due to more frequent gradient updates and emphasizes exploitation later on with longer trajectories. In gridworld, simulated robotic environments, and real-world robotic experiments, we demonstrate the merits of the approach over constant and randomly sampled trajectory lengths in terms of performance and sample efficiency. For a fixed sample budget, Ada-NAV results in an 18% increase in navigation success rate, a 20-38% decrease in the navigation path length, and 9.32% decrease in the elevation cost compared to the policies obtained by the other methods. We also demonstrate that Ada-NAV can be transferred and integrated into a Clearpath Husky robot without significant performance degradation.
Principles and roles of mRNA localization in animal development

Intracellular targeting of mRNAs has long been recognized as a means to produce proteins locally, but has only recently emerged as a prevalent mechanism used by a wide variety of polarized cell types. Localization of mRNA molecules within the cytoplasm provides a basis for cell polarization, thus underlying developmental processes such as asymmetric cell division, cell migration, neuronal maturation and embryonic patterning. In this review, we describe and discuss recent advances in our understanding of both the regulation and functions of RNA localization during animal development.
Sfi1p has conserved centrin-binding sites and an essential function in budding yeast spindle pole body duplication

Centrins are calmodulin-like proteins present in microtubule-organizing centers. The Saccharomyces cerevisiae centrin, Cdc31p, was functionally tagged with a single Z domain of protein A, and used in pull-down experiments to isolate Cdc31p-binding proteins. One of these, Sfi1p, localizes to the half-bridge of the spindle pole body (SPB), where Cdc31p is also localized. Temperature-sensitive mutants in SFI1 show a defect in SPB duplication and genetic interactions with cdc31-1. Sfi1p contains multiple internal repeats that are also present in a Schizosaccharomyces pombe protein, which also localizes to the SPB, and in several human proteins, one of which localizes close to the centriole region. Cdc31p binds directly to individual Sfi1 repeats in a 1:1 ratio, so a single molecule of Sfi1p binds multiple molecules of Cdc31p. The centrosomal human protein containing Sfi1 repeats also binds centrin in the repeat region, showing that this centrin-binding motif is conserved.
A Single Image Interpolation Scheme for Enhanced Super Resolution in Bio-Medical Imaging

In this paper we illustrate a novel image interpolation method based on the amalgamation of bicubic interpolation and 2D interpolation filter. First, bicubic interpolation algorithm is applied interpolating pixels to create a high resolution image. Then 2D interpolation filter algorithm is applied along columns and rows modifying the interpolated values to produce super resolution image. The second algorithm preserves edge smoothness and refines the interpolated pixels to produce visually high quality images. The results demonstrate that our new interpolation algorithm significantly enhances the quality and Peak Signal to Noise Ratio (PSNR) of the interpolated images over ICBI and iNEDI interpolation methods.
Effects of LSD on music-evoked brain activity

Music is a highly dynamic stimulus, and consists of distinct acoustic features, such as pitch, rhythm and timbre. Neuroimaging studies highlight a hierarchy of brain networks involved in music perception. Psychedelic drugs such as lysergic acid diethylamide (LSD) temporary disintegrate the normal hierarchy of brain functioning, and produce profound subjective effects, including enhanced music-evoked emotion. The primary objective of this study was to investigate the acute effects of LSD on music-evoked brain-activity under naturalistic music listening conditions. 16 healthy participants were enrolled in magnetic resonance imaging (fMRI) while listening to a 7-minute music piece under eyes-closed conditions on two separate visits (LSD (75 mcg) and placebo). Dynamic time courses for acoustic features were extracted from the music excerpts, and were entered into subject-level fMRI analyses as regressors of interest. Differences between conditions were assessed at group level subsequently, and were related to changes in music-evoked emotions via correlation analyses. Psycho-physiological interactions (PPIs) were carried out to further interrogate underlying music-specific changes in functional connectivity under LSD. Results showed pronounced cortical and subcortical changes in music-evoked brain activity under LSD. Most notable changes in brain activity and connectivity were associated with the component timbral complexity, representing the complexity of the music’s spectral distribution, and these occurred in brain networks previously identified for music-perception and music-evoked emotion, and showed an association with enhanced music-evoked feelings of wonder under LSD. The findings shed light on how the brain processes music under LSD, and provide a neurobiological basis for the usefulness of music in psychedelic therapy.
Localized Basaloid Follicular Hamartoma

We report a 39‐year‐old Japanese woman with a 30 × 10 mm, skin‐colored, soft, hairless, irregularly elevated plaque in the left retroauricular area. Histologically, it consistently showed features of atypical hair follicles; some showed immaturely developed basaloid epithelial islands invaginated with condensed stromal cells, and others were replaced or associated with solid strands, branching cords, or lace‐like networks of undifferentiated basaloid cells. Although the clinical appearance of a typical localized basaloid follicular hamartoma is a plaque of alopecia, this case seems to be a variant, because the histological findings are so characteristic of the entity. The relationship of basaloid follicular hamartoma to other hair‐follicle derived tumors is also considered.
Automated detection of injected faults in a differential equation solver

Analysis of logical relationships between inputs and outputs of a computational system can significantly reduce the test execution effort via minimizing the number of required test cases. Unfortunately, the available specification documents are often insufficient to build a complete and reliable model of the tested system. In this paper, we demonstrate the use of a data mining method, called Info-Fuzzy Network (IFN), which can automatically induce logical dependencies from execution data of a stable software version, construct a set of non-redundant test cases, and identify faulty outcomes in new, potentially faulty releases of the same system. The proposed approach is applied to the Unstructured Mesh Finite Element Solver (UMFES) which is a general finite element program for solving 2D elliptic partial differential equations. Experimental results demonstrate the capability of the IFN-based testing methodology to detect several kinds of faults injected in the code of this sophisticated application.
Stathmin regulates mutant p53 stability and transcriptional activity in ovarian cancer

Stathmin is a p53‐target gene, frequently overexpressed in late stages of human cancer progression. Type II High Grade Epithelial Ovarian Carcinomas (HG‐EOC) represents the only clear exception to this observation. Here, we show that stathmin expression is necessary for the survival of HG‐EOC cells carrying a p53 mutant (p53MUT) gene. At molecular level, stathmin favours the binding and the phosphorylation of p53MUT by DNA‐PKCS, eventually modulating p53MUT stability and transcriptional activity. Inhibition of stathmin or DNA‐PKCS impaired p53MUT–dependent transcription of several M phase regulators, resulting in M phase failure and EOC cell death, both in vitro and in vivo. In primary human EOC a strong correlation exists between stathmin, DNA‐PKCS, p53MUT overexpression and its transcriptional targets, further strengthening the relevance of the new pathway here described. Overall our data support the hypothesis that the expression of stathmin and p53 could be useful for the identification of high risk patients that will benefit from a therapy specifically acting on mitotic cancer cells.
Simultaneous peak and average power minimization during datapath scheduling

In low-power design for deep submicrometer and nanometer regimes, peak power, power fluctuation, average power, and total energy are equally important design constraints. In this paper, we propose datapath scheduling algorithms for simultaneous minimization of peak and average power. The minimization schemes based on integer linear programming are developed for the design of datapaths that can function in three modes of operation: 1) single supply voltage and single frequency; 2) multiple supply voltages and dynamic frequency clocking (MVDFC); and 3) multiple supply voltages and multicycling. The techniques are evaluated by estimating the peak power consumption, the average power consumption and the power delay product of selected high level synthesis benchmark circuits for different resource constraints. Experimental results indicate that combining multiple voltages and dynamic frequency clocking as in the MVDFC scheme, yields significant reductions in the peak power, the average power, and the power delay product.
Raghu Ramakrishnan speaks out on deductive databases, what lies beyond scalability, how he burned through $20M briskly, why we should reach out to policymakers, and more

Welcome to this installment of ACM SIGMOD Record's series of interviews with distinguished members of the database community. I'm Marianne Winslett, and today we are at the Department of Computer Science at the University of Illinois at Urbana-Champaign. I have here with me Raghu Ramakrishnan, who is a Professor of Computer Sciences at the University of Wisconsin-Madison. Raghu's research currently focuses on data retrieval and integration, analysis, and mining. Raghu was a founder of QUIQ, a company that developed a collaborative customer support facility. Raghu has received the National Science Foundation's Presidential Young Investigator award, a Packard Fellowship, and a SIGMOD Contributions Award for founding and maintaining DBWorld. Raghu is an ACM Fellow; he is a coauthor of the popular Database Management Systems textbook; and he is also the current chair of ACM SIGMOD. Raghu's PhD is from the University of Texas at Austin. So, Raghu, welcome!