Miracle-dz/UniFAR-FTUs huggingface dataset:
High-Throughput Plasmodium falciparum Growth Assay for Malaria Drug Discovery

ABSTRACT New therapeutic agents for the treatment of malaria, the world's most deadly parasitic disease, are urgently needed. Malaria afflicts 300 to 500 million people and results in 1 to 2 million deaths annually, and more than 85% of all malaria-related mortality involves young children and pregnant women in sub-Saharan Africa. The emergence of multidrug-resistant parasites, especially in Plasmodium falciparum, has eroded the efficacy of almost all currently available therapeutic agents. The discovery of new drugs, including drugs with novel cellular targets, could be accelerated with a whole-organism high-throughput screen (HTS) of structurally diverse small-molecule libraries. The standard whole-organism screen is based on incorporation of [3H]hypoxanthine and has liabilities, such as limited throughput, high cost, multiple labor-intensive steps, and disposal of radioactive waste. Recently, screens have been reported that do not use radioactive incorporation, but their reporter signal is not robust enough for HTS. We report a P. falciparum growth assay that is technically simple, robust, and compatible with the automation necessary for HTS. The assay monitors DNA content by addition of the fluorescent dye 4′,6-diamidino-2-phenylindole (DAPI) as a reporter of blood-stage parasite growth. This DAPI P. falciparum growth assay was used to measure the 50% inhibitory concentrations (IC50s) of a diverse set of known antimalarials. The resultant IC50s compared favorably with those obtained in the [3H]hypoxanthine incorporation assay. Over 79,000 small molecules have been tested for antiplasmodial activity using the DAPI P. falciparum growth assay, and 181 small molecules were identified as highly active against multidrug-resistant parasites.
Carotid Intima-Media Thickness at Age 30, Birth Weight, Accelerated Growth during Infancy and Breastfeeding: A Birth Cohort Study in Southern Brazil

Objective To examine the relationship between carotid intima-media thickness (IMT) at age 30 and birth characteristics, growth during infancy, and breastfeeding duration, among subjects who have been prospectively followed since birth. Methods and Results In 1982, all births in the city of Pelotas, southern Brazil, were identified and those children (n = 5,914) whose families lived in the urban area of the city have been followed and evaluated at several time points. The cohort participants were evaluated in 2012–13, and IMT was measured at the posterior wall of the right and left common carotid arteries in longitudinal planes using ultrasound imaging. We obtained valid IMT measurements for 3,188 individuals. Weight-for-age z-score (WAZ) at age 2 years, weight-for-height z-score (WHZ) at age 4, height-for-age z-score (HAZ) at 4 years, WAZ at age 4 and relative conditional weight at 4 years were positively associated with IMT, even after controlling for confounding variables. The beta-coefficient associated with ≥1 s.d. WAZ at age 2 (compared to those with a <–1 s.d.) was 3.62 μm (95% CI 0.86 to 6.38). The beta-coefficient associated with ≥1 s.d. WHZ at 4 (in relation to <–1 s.d) was 3.83 μm (95% CI 0.24 to 7.42). For HAZ at 4, the beta-coefficient for ≥1 s.d. in relation to <–1 s.d. was 4.19 μm (95% CI 1.14 to 7.25). For WAZ at 4, the beta-coefficient associated with ≥1 s.d. in relation to <–1 s.d. was 4.28 μm (95% CI 1.59 to 6.97). The beta-coefficient associated with conditional weight gain at age 2–4 was 1.26 μm (95% CI 0.49 to 2.02). Conclusion IMT at age 30 was positively associated with WAZ at age 2 years, WHZ at age 4, HAZ at age 4, WAZ at age 4 and conditional weight gain at age 4 years.
ELECTROCATALYTICAL MAGNETOBIOSENSING BASED ON GOLD NANOPARTICLES

In this work, electrocatalytical methods are developed in order to improve the sensitivity of model biosensors based on a labelling method using AuNPs. Microparamagnetic beads (MB) are used as primary biological molecules immobilisation platforms and AuNPs modified with secondary biological molecules as high sensitive electrochemical labels. The carbon electrodes, used as transducer, incorporate a magnet that allows the collection / immobilization on its surface of the biological sandwich attached to the MB. The final detection is based on the catalytic effect of AuNPs on the electroreduction of different species, like silver ions. The low levels of AuNPs detected with these methods allow the obtaining of biosensors with low protein and ssDNA target detection limits, with special interest for further applications in clinical analysis, food quality and safety as well as other industrial applications.
Memory formation: from network structure to neural dynamics

Understanding the neural correlates of brain function is an extremely challenging task, since any cognitive process is distributed over a complex and evolving network of neurons that comprise the brain. In order to quantify observed changes in neuronal dynamics during hippocampal memory formation, we present metrics designed to detect directional interactions and the formation of functional neuronal ensembles. We apply these metrics to both experimental and model-derived data in an attempt to link anatomical network changes with observed changes in neuronal dynamics during hippocampal memory formation processes. We show that the developed model provides a consistent explanation of the anatomical network modifications that underlie the activity changes observed in the experimental data.
Structure of the mitochondrial ATP synthase from Pichia angusta determined by electron cryo-microscopy

Significance Living cells need fuel in the form of adenosine triphosphate, or ATP, to stay alive. This fuel is generated by a molecular machine made of two motors joined by a rotor. One generates rotation by using energy provided by oxidative metabolism or photosynthesis; the other uses energy transmitted by the rotor to make ATP molecules from its building blocks, adenosine diphosphate, or ADP, and inorganic phosphate. The structure has been determined of a fungal machine, isolated from its cellular power stations, the mitochondria, where the machine operates. It provides unsuspected details of the blueprint of the machine and how it works. The working principles of the fungal machine apply to similar machines in all species. The structure of the intact monomeric ATP synthase from the fungus, Pichia angusta, has been solved by electron cryo-microscopy. The structure provides insights into the mechanical coupling of the transmembrane proton motive force across mitochondrial membranes in the synthesis of ATP. This mechanism requires a strong and integral stator, consisting of the catalytic α3β3-domain, peripheral stalk, and, in the membrane domain, subunit a and associated supernumerary subunits, kept in contact with the rotor turning at speeds up to 350 Hz. The stator’s integrity is ensured by robust attachment of both the oligomycin sensitivity conferral protein (OSCP) to the catalytic domain and the membrane domain of subunit b to subunit a. The ATP8 subunit provides an additional brace between the peripheral stalk and subunit a. At the junction between the OSCP and the apparently stiff, elongated α-helical b-subunit and associated d- and h-subunits, an elbow or joint allows the stator to bend to accommodate lateral movements during the activity of the catalytic domain. The stator may also apply lateral force to help keep the static a-subunit and rotating c10-ring together. The interface between the c10-ring and the a-subunit contains the transmembrane pathway for protons, and their passage across the membrane generates the turning of the rotor. The pathway has two half-channels containing conserved polar residues provided by a bundle of four α-helices inclined at ∼30° to the plane of the membrane, similar to those described in other species. The structure provides more insights into the workings of this amazing machine.
Endophyte-Mediated Modulation of Defense-Related Genes and Systemic Resistance in Withania somnifera (L.) Dunal under Alternaria alternata Stress

ABSTRACT Endophytes have been explored and found to perform an important role in plant health. However, their effects on the host physiological function and disease management remain elusive. The present study aimed to assess the potential effects of endophytes, singly as well as in combination, in Withania somnifera (L.) Dunal, on various physiological parameters and systemic defense mechanisms against Alternaria alternata. Seeds primed with the endophytic bacteria Bacillus amyloliquefaciens and Pseudomonas fluorescens individually and in combination demonstrated an enhanced vigor index and germination rate. Interestingly, plants treated with the two-microbe combination showed the lowest plant mortality rate (28%) under A. alternata stress. Physiological profiling of treated plants showed improved photosynthesis, respiration, transpiration, and stomatal conductance under pathogenic stress. Additionally, these endophytes not only augmented defense enzymes and antioxidant activity in treated plants but also enhanced the expression of salicylic acid- and jasmonic acid-responsive genes in the stressed plants. Reductions in reactive oxygen species (ROS) and reactive nitrogen species (RNS) along with enhanced callose deposition in host plant leaves corroborated well with the above findings. Altogether, the study provides novel insights into the underlying mechanisms behind the tripartite interaction of endophyte-A. alternata-W. somnifera and underscores their ability to boost plant health under pathogen stress. IMPORTANCE W. somnifera is well known for producing several medicinally important secondary metabolites. These secondary metabolites are required by various pharmaceutical sectors to produce life-saving drugs. However, the cultivation of W. somnifera faces severe challenge from leaf spot disease caused by A. alternata. To keep pace with the rising demand for this plant and considering its capacity for cultivation under field conditions, the present study was undertaken to develop approaches to enhance production of W. somnifera through intervention using endophytes. Application of bacterial endophytes not only suppresses the pathogenicity of A. alternata but also mitigates excessive ROS/RNS generation via enhanced physiological processes and antioxidant machinery. Expression profiling of plant defense-related genes further validates the efficacy of bacterial endophytes against leaf spot disease.
Reinforcement Learning with Function-Valued Action Spaces for Partial Differential Equation Control

Recent work has shown that reinforcement learning (RL) is a promising approach to control dynamical systems described by partial differential equations (PDE). This paper shows how to use RL to tackle more general PDE control problems that have continuous high-dimensional action spaces with spatial relationship among action dimensions. In particular, we propose the concept of action descriptors, which encode regularities among spatially-extended action dimensions and enable the agent to control high-dimensional action PDEs. We provide theoretical evidence suggesting that this approach can be more sample efficient compared to a conventional approach that treats each action dimension separately and does not explicitly exploit the spatial regularity of the action space. The action descriptor approach is then used within the deep deterministic policy gradient algorithm. Experiments on two PDE control problems, with up to 256-dimensional continuous actions, show the advantage of the proposed approach over the conventional one.
IQA: Visual Question Answering in Interactive Environments

We introduce Interactive Question Answering (IQA), the task of answering questions that require an autonomous agent to interact with a dynamic visual environment. IQA presents the agent with a scene and a question, like: "Are there any apples in the fridge? " The agent must navigate around the scene, acquire visual understanding of scene elements, interact with objects (e.g. open refrigerators) and plan for a series of actions conditioned on the question. Popular reinforcement learning approaches with a single controller perform poorly on IQA owing to the large and diverse state space. We propose the Hierarchical Interactive Memory Network (HIMN), consisting of a factorized set of controllers, allowing the system to operate at multiple levels of temporal abstraction. To evaluate HIMN, we introduce IQUAD V1, a new dataset built upon AI2-THOR [35], a simulated photo-realistic environment of configurable indoor scenes with interactive objects. IQUAD V1 has 75,000 questions, each paired with a unique scene configuration. Our experiments show that our proposed model outperforms popular single controller based methods on IQUAD V1. For sample questions and results, please view our video: https://youtu.be/pXd3C-1jr98.
A Distributed Algorithm for Mining Fuzzy Association Rules

Data mining, also known as knowledge discovery in databases, is the process of discovery potentially useful, hidden knowledge or relations among data from large databases. An important topic in data mining research is concerned with the discovery of association rules. The majority of databases are distributed nowadays. In this paper is presented an algorithm for mining fuzzy association rules from these distributed databases. This algorithm is inspired from DMA ( DistributedMining of Association rules) algorithm for mining boolean association rules.
Equalization for OFDM over doubly selective channels

In this paper, we propose a time-domain as well as a frequency-domain per-tone equalization for orthogonal frequency-division multiplexing (OFDM) over doubly selective channels. We consider the most general case, where the channel delay spread is larger than the cyclic prefix (CP), which results in interblock interference (IBI). IBI in conjunction with the Doppler effect destroys the orthogonality between subcarriers and, hence, results in severe intercarrier interference (ICI). In this paper, we propose a time-varying finite-impulse-response (TV-FIR) time-domain equalizer (TEQ) to restore the orthogonality between subcarriers, and hence to eliminate ICI/IBI. Due to the fact that the TEQ optimizes the performance over all subcarriers in a joint fashion, it has a poor performance. An optimal frequency-domain per-tone equalizer (PTEQ) is then obtained by transferring the TEQ operation to the frequency domain. Through computer simulations, we demonstrate the performance of the proposed equalization techniques.
Digital Zombies - the Reanimation of our Digital Selves

What happens to our social media profiles when we die The episode "Be Right Back" as part of Netflix's series "Black Mirror" provides a possible scenario. A digital avatar is created to communicate with close relatives which learns from past social media activities of the deceased user. While the users entrust their social media content to one or more companies, even after their death, it may be reasonable to ask: What will the company really do with a deceased user's data: sell it to manipulate users or create advertisements In this paper we tackle the issues of ownership, ethics, and transparency of post mortem user data.
Fungemia Surveillance in Denmark Demonstrates Emergence of Non-albicans Candida Species and Higher Antifungal Usage and Resistance Rates than in Other Nations

ABSTRACT Recent changes in the occurrence of fungal species and the difficulties in performing reference antifungal susceptibility testing highlight the importance of surveillance of fungal organisms and antifungal resistance rates. K. M. T. Astvad et al. report results from recent (2012 to 2015) fungemia surveillance in Denmark and compare the results to previous data (2004 to 2011), showing a decrease in Candida albicans infections accompanied by an increase in C. glabrata and C. dubliniensis infections (J Clin Microbiol 56:e01564-17, 2018, https://doi.org/10.1128/JCM.01564-17). Azole resistance among C. tropicalis and C. parapsilosis isolates and echinocandin resistance in C. krusei isolates were higher in Denmark than in other regions. Interestingly, the usage of antifungals is higher in Denmark than in other Nordic countries.
YY1 and CTCF orchestrate a 3D chromatin looping switch during early neural lineage commitment

CTCF is an architectural protein with a critical role in connecting higher-order chromatin folding in pluripotent stem cells. Recent reports have suggested that CTCF binding is more dynamic during development than previously appreciated. Here, we set out to understand the extent to which shifts in genome-wide CTCF occupancy contribute to the 3D reconfiguration of fine-scale chromatin folding during early neural lineage commitment. Unexpectedly, we observe a sharp decrease in CTCF occupancy during the transition from naïve/primed pluripotency to multipotent primary neural progenitor cells (NPCs). Many pluripotency gene-enhancer interactions are anchored by CTCF, and its occupancy is lost in parallel with loop decommissioning during differentiation. Conversely, CTCF binding sites in NPCs are largely preexisting in pluripotent stem cells. Only a small number of CTCF sites arise de novo in NPCs. We identify another zinc finger protein, Yin Yang 1 (YY1), at the base of looping interactions between NPC-specific genes and enhancers. Putative NPC-specific enhancers exhibit strong YY1 signal when engaged in 3D contacts and negligible YY1 signal when not in loops. Moreover, siRNA knockdown of Yy1 specifically disrupts interactions between key NPC enhancers and their target genes. YY1-mediated interactions between NPC regulatory elements are often nested within constitutive loops anchored by CTCF. Together, our results support a model in which YY1 acts as an architectural protein to connect developmentally regulated looping interactions; the location of YY1-mediated interactions may be demarcated in development by a preexisting topological framework created by constitutive CTCF-mediated interactions.
Distinguishing facts from beliefs: fuzzy categories

Abstract This paper presents results from five studies that investigate how people perceive the distinction between facts and beliefs. The central question being asked is whether the features that distinguish the categories of facts and beliefs are distinct or overlapping. In each of the five studies, participants are presented with content statements and asked the degree to which they agree with a given statement, the degree to which they think others would agree with it, and whether the statement was a fact or a belief. From these ratings, six possible patterns were derived. The results showed that in many content areas the patterns that describe the statements they categorized as facts and those that they categorized as beliefs had considerable overlap. In addition, participant consensus as to which statements were to be considered facts versus beliefs varied from high to low depending on the specific content being evaluated.
Robot Behavior Planning by a Coordinator Robot in a Symbiotic Autonomous Human-Robot System

This paper addresses robot behavior planning by a coordinator robot in a symbiotic autonomous human-robot system according to human requests. A coordinator robot is constructed based on the knowledge representation of coordination which is a description world to describe a physical domain world on coordination, including interpreter for the human request domain, coordination interface for the problem domain, coordination policy for the solution domain, etc. The coordination policy in the model is adopted for planning robot behaviors by a coordinator robot. By means of a software platform and distributed intelligent agents, a coordinator robot can be implemented and the robot behavior planning can be carried out according to human requests. In this paper, a coordinator robot is actually constructed and it can autonomously plan robot behaviors in a symbiotic autonomous human-robot system. The experimental work demonstrates the effectiveness of the proposed method.
Seven-Up Is a Novel Regulator of Insulin Signaling

Musselman et al. address the overarching question: “What’s so bad about a high-calorie diet? ” Using computational biology to analyze mRNA expression profiles, the authors built a Drosophila fat body gene regulatory network that predicted. Insulin resistance is associated with obesity, cardiovascular disease, non-alcoholic fatty liver disease, and type 2 diabetes. These complications are exacerbated by a high-calorie diet, which we used to model type 2 diabetes in Drosophila melanogaster. Our studies focused on the fat body, an adipose- and liver-like tissue that stores fat and maintains circulating glucose. A gene regulatory network was constructed to predict potential regulators of insulin signaling in this tissue. Genomic characterization of fat bodies suggested a central role for the transcription factor Seven-up (Svp). Here, we describe a new role for Svp as a positive regulator of insulin signaling. Tissue-specific loss-of-function showed that Svp is required in the fat body to promote glucose clearance, lipid turnover, and insulin signaling. Svp appears to promote insulin signaling, at least in part, by inhibiting ecdysone signaling. Svp also impairs the immune response possibly via inhibition of antimicrobial peptide expression in the fat body. Taken together, these studies show that gene regulatory networks can help identify positive regulators of insulin signaling and metabolic homeostasis using the Drosophila fat body.
SCHEME OF AN ALGORITHM FOR THE SUPPRESSION OF ENVIRONMENTAL NOISE IN HEARING DEVICES 1

At present, noise pollution is a relevant factor to measure the quality of life of people. In order to solve this problem, in this article an algorithm is proposed that allows to filter the unwanted noise levels and to admit the flow to the sounds that are required. The algorithm is based on the amplification and filtering techniques that are provided by the operational amplifiers. The function of the algorithm is divided into two parts: it first filters out the frequencies that are not wanted (environmental noise) and then amplifies the frequencies that are required (conversations, sounds very close to the user); the output signal is evaluated by calculating the ODG (Objective Difference Grade) as regulated by the ITU (International Telecommunications Union). The average ODG obtained was -0.946, the previous result indicates that the output signal of the algorithm (clean signal of noise) with respect to the input signal (signal with noise attached) has been correctly filtered such that the noise is slightly perceptible but not annoying to Human Auditory System (HAS). The algorithm was designed using ORCAD® and the subjective test was the MOS (Mean Opinion Score) with people who have suffered various hearing loss.
In Situ‐Forming Cross‐linking Hydrogel Systems: Chemistry and Biomedical Applications

With the development of chemical synthetic strategies and available building blocks, in situ‐forming hydrogels have attracted significant attention in the biomedical fields over the past decade. Due to their distinct properties of easy management and minimal invasiveness via simple aqueous injections at target sites, in situ‐forming hydrogels have found a broad spectrum of biomedical applications including tissue engineering, drug delivery, gene delivery, 3D bioprinting, wound healing, antimicrobial research, and cancer research. The objective of this chapter is to provide a comprehensive review of updated research methods in chemical synthesis of in situ‐forming cross‐linking hydrogel systems and their diverse applications in the biomedical fields. This chapter concludes with perspectives on the future development of in situ‐forming hydrogels to facilitate this multidisciplinary field.