Miracle-dz/UniFAR-FTUs huggingface dataset:
Investigating Sulfoxide-to-Sulfone Conversion as a Prodrug Strategy for a Phosphatidylinositol 4-Kinase Inhibitor in a Humanized Mouse Model of Malaria

The in vivo antimalarial efficacies of two phosphatidylinositol 4-kinase (PI4K) inhibitors, a 3,5-diaryl-2-aminopyrazine sulfoxide and its corresponding sulfone metabolite, were evaluated in the NOD-scid IL2Rγnull (NSG) murine malaria disease model of Plasmodium falciparum infection. We hypothesized that the sulfoxide would serve as a more soluble prodrug for the sulfone, which would lead to improved drug exposure with oral dosing. ABSTRACT The in vivo antimalarial efficacies of two phosphatidylinositol 4-kinase (PI4K) inhibitors, a 3,5-diaryl-2-aminopyrazine sulfoxide and its corresponding sulfone metabolite, were evaluated in the NOD-scid IL2Rγnull (NSG) murine malaria disease model of Plasmodium falciparum infection. We hypothesized that the sulfoxide would serve as a more soluble prodrug for the sulfone, which would lead to improved drug exposure with oral dosing. Both compounds had similar efficacy (90% effective dose [ED90], 0.1 mg kg–1 of body weight) across a quadruple-dose regimen. Pharmacokinetic profiling revealed rapid sulfoxide clearance via conversion to sulfone, with sulfone identified as the major active metabolite. When the sulfoxide was dosed, the exposure of the sulfone achieved was as much as 2.9-fold higher than when the sulfone was directly dosed, thereby demonstrating that the sulfoxide served as an effective prodrug for the treatment of malaria.
Homotypic and heterotypic continuity of internalizing and externalizing symptoms from ages 3 to 12: The moderating role of diurnal cortisol

Abstract Psychological symptoms that arise in early childhood can follow a multitude of patterns into adolescence, including homotypic continuity (i.e., similar symptoms over time) and heterotypic continuity (i.e., a shift in symptoms over time). However, we know very little about the factors that distinguish homotypic vs. heterotypic continuity of early internalizing and externalizing symptoms over development. In a separate line of research, diurnal cortisol has been shown to predict later internalizing and externalizing problems. In the current study, we tested whether diurnal cortisol patterns moderated the course of internalizing and externalizing symptoms from preschool to early adolescence. 554 children (54% male) and parents participated in a longitudinal study. Parents reported on their children’s internalizing and externalizing symptoms at ages 3 and 12, and children collected diurnal saliva samples at age 9. Results showed that a steeper cortisol decline at age 9 combined with high internalizing or externalizing problems at age 3 predicted higher internalizing problems at age 12. A more blunted cortisol decline combined with early internalizing or externalizing problems predicted higher externalizing problems in early adolescence. These results illustrate the moderating role of stress system functioning in homotypic and heterotypic patterns of psychopathology from preschool to early adolescence.
What do usability test moderators say?: 'mm hm', 'uh-huh', and beyond

Moderators in usability tests wrestle with the conflicting goals of obtaining relevant information from the users while at the same time avoiding to influence the users in ways that change how they use and feel about the tested system. In this study we investigate what moderators say by categorizing the moderator verbalizations from 12 test sessions. During the test tasks affirmations (38%) were the most common moderator verbalizations, followed by task instructions (32%) and prompts for reflection (16%). In addition, more of the moderator verbalizations during the tasks were closed (31%) than open (14%) and many more were positive (16%) than negative (1%). The moderators verbalized at a lower rate during the tasks than in the part of the sessions before the first task and after the last task. Still, they talked quite a lot. We discuss the content of their verbalizations and the implications of our findings.
Which Source Code Plagiarism Detection Approach is More Humane?

This paper contributes in developing source code plagiarism detection that is more aligned with human perspective. Three evaluation mechanisms that directly relate human perspective with evaluated approaches are proposed: think-aloud, aspectoriented, and empirical mechanism. Using those mechanisms, a comparative study toward attribute-and structure-based plagiarism detection approach (i.e., two popular approach categories in source code plagiarism detection) is conducted. According to that study, structure-based approach is more effective than the attribute-based one; its signature aspect and resulted similarity degrees are more related to human preferences. In addition, such approach is related to most human-oriented aspects for suspecting source code plagiarism.
Norm-Ranging LSH for Maximum Inner Product Search

Neyshabur and Srebro proposed SIMPLE-LSH, which is the state-of-the-art hashing based algorithm for maximum inner product search (MIPS). We found that the performance of SIMPLE-LSH, in both theory and practice, suffers from long tails in the 2-norm distribution of real datasets. We propose NORM-RANGING LSH, which addresses the excessive normalization problem caused by long tails by partitioning a dataset into sub-datasets and building a hash index for each sub-dataset independently. We prove that NORM-RANGING LSH achieves lower query time complexity than SIMPLE-LSH under mild conditions. We also show that the idea of dataset partitioning can improve another hashing based MIPS algorithm. Experiments show that NORM-RANGING LSH probes much less items than SIMPLE-LSH at the same recall, thus significantly benefiting MIPS based applications.
A Novel PAA Derivative with Enhanced Drug Efficacy in Pancreatic Cancer Cell Lines

Nanoparticles have been shown to be effective drug carriers in cancer therapy. Pancreatic cancer forms dense tumours which are often resistant to drug molecules. In order to overcome such multidrug resistance, new drug entities, novel delivery systems and combination therapy strategies are being explored. In this paper, we report the design and synthesis of a poly(allylamine)-based amphiphile modified with hydrophobic naphthalimido pendant groups. Bisnaphthalimide compounds have been shown to possess anticancer activity. The potential of this polymer to encapsulate, solubilize and enhance drug (5-fluorouricil and bis-(naphthalimidopropyl)-diaminooctane) cytotoxicity in BxPC-3 cells was evaluated. Our studies showed that the insoluble drugs could be formulated up to 4.3 mg mL−1 and 2.4 mg mL−1 inside the amphiphiles, respectively. Additionally, the novel poly(allylamine)-naphthalimide carrier resulted in an amplification of cytotoxic effect with drug treatment after 24 h, and was capable of reduction of 50% cell population at concentrations as low as 3 μg mL−1.
Specificity of Primate Amygdalar Pathways to Hippocampus

The amygdala projects to hippocampus in pathways through which affective or social stimuli may influence learning and memory. We investigated the still unknown amygdalar termination patterns and their postsynaptic targets in hippocampus from system to synapse in rhesus monkeys of both sexes. The amygdala robustly innervated the stratum lacunosum-moleculare layer of cornu ammonis fields and uncus anteriorly. Sparser terminations in posterior hippocampus innervated the radiatum and pyramidal layers at the prosubicular/CA1 juncture. The terminations, which were larger than other afferents in the surrounding neuropil, position the amygdala to influence hippocampal input anteriorly, and its output posteriorly. Most amygdalar boutons (76–80%) innervated spines of excitatory hippocampal neurons, and most of the remaining innervated presumed inhibitory neurons, identified by morphology and label with parvalbumin or calretinin, which distinguished nonoverlapping neurochemical classes of hippocampal inhibitory neurons. In CA1, amygdalar axons innervated some calretinin neurons, which disinhibit pyramidal neurons. By contrast, in CA3 the amygdala innervated both calretinin and parvalbumin neurons; the latter strongly inhibit nearby excitatory neurons. In CA3, amygdalar pathways also made closely spaced dual synapses on excitatory neurons. The strong excitatory synapses in CA3 may facilitate affective context representations and trigger sharp-wave ripples associated with memory consolidation. When the amygdala is excessively activated during traumatic events, the specialized innervation of excitatory neurons and the powerful parvalbumin inhibitory neurons in CA3 may allow the suppression of activity of nearby neurons that receive weaker nonamygdalar input, leading to biased passage of highly charged affective stimuli and generalized fear. SIGNIFICANCE STATEMENT Strong pathways from the amygdala targeted the anterior hippocampus, and more weakly its posterior sectors, positioned to influence a variety of emotional and cognitive functions. In hippocampal field CA1, the amygdala innervated some calretinin neurons, which disinhibit excitatory neurons. By contrast, in CA3 the amygdala innervated calretinin as well as some of the powerful parvalbumin inhibitory neurons and may help balance the activity of neural ensembles to allow social interactions, learning, and memory. These results suggest that when the amygdala is hyperactive during emotional upheaval, it strongly activates excitatory hippocampal neurons and parvalbumin inhibitory neurons in CA3, which can suppress nearby neurons that receive weaker input from other sources, biasing the passage of stimuli with high emotional import and leading to generalized fear.
Wasserstein Distributionally Robust Kalman Filtering

We study a distributionally robust mean square error estimation problem over a nonconvex Wasserstein ambiguity set containing only normal distributions. We show that the optimal estimator and the least favorable distribution form a Nash equilibrium. Despite the non-convex nature of the ambiguity set, we prove that the estimation problem is equivalent to a tractable convex program. We further devise a Frank-Wolfe algorithm for this convex program whose direction-searching subproblem can be solved in a quasi-closed form. Using these ingredients, we introduce a distributionally robust Kalman filter that hedges against model risk.
Electromagnetic Shielding by MXene-Graphene-PVDF Composite with Hydrophobic, Lightweight and Flexible Graphene Coated Fabric

MXene and graphene based thin, flexible and low-density composite were prepared by cost effective spray coating and solvent casting method. The fabricated composite was characterized using Raman spectroscopy, X-ray diffraction (XRD), scanning electron microscope (SEM), X-ray photoelectron spectroscopy (XPS) and energy dispersive X-ray (EDX). The prepared composites showed hydrophobic nature with higher contact angle of 126°, −43 mN·m−1 wetting energy, −116 mN·m−1 spreading Coefficient and 30 mN·m−1 lowest work of adhesion. The composites displayed excellent conductivity of 13.68 S·cm−1 with 3.1 Ω·sq−1 lowest sheet resistance. All the composites showed an outstanding thermal stability and constrain highest weight lost until 400 °C. The MXene-graphene foam exhibited excellent EMI shielding of 53.8 dB (99.999%) with reflection of 13.10 dB and absorption of 43.38 dB in 8–12.4 GHz. The single coated carbon fabric displayed outstanding absolute shielding effectiveness of 35,369.82 dB·cm2·g−1. The above results lead perspective applications such as aeronautics, radars, air travels, mobile phones, handy electronics and military applications.
Invited: Reconciling Remote Attestation and Safety-Critical Operation on Simple IoT Devices

Remote attestation (RA) is a means of malware detection, typically realized as an interaction between a trusted verifier and a potentially compromised remote device (prover). RA is especially relevant for low-end embedded devices that are incapable of protecting themselves against malware infection. Most current RA techniques require on-demand and uninterruptible (atomic) operation. The former fails to detect transient malware that enters and leaves between successive RA instances; the latter involves performing potentially time-consuming computation over prover's memory and/or storage, which can be harmful to the device's safety-critical functionality and general availability. However, relaxing either on-demand or atomic RA operation is tricky and prone to vulnerabilities. This paper identifies some issues that arise in reconciling requirements of safety-critical operation with those of secure remote attestation, including detection of transient and self-relocating malware. It also investigates mitigation techniques, including periodic self-measurements as well as interruptible attestation modality that involves shuffled memory traversals and various memory locking mechanisms.
Aquatic insects rich in omega-3 fatty acids drive breeding success in a widespread bird.

Ecologists studying bird foraging ecology have generally focused on food quantity over quality. Emerging work suggests that food quality, in terms of highly unsaturated omega-3 fatty acids (HUFA), can have equally important effects on performance. HUFA, which are present in aquatic primary producers, are all but absent in vascular plants, and HUFA content is also correspondingly higher in aquatic insects. Here, we show that Tree Swallow (Tachycineta bicolor) chicks rapidly accumulate HUFA from food during the nestling period. Using data sampled over 24 years, we also show that Tree Swallow breeding success is positively associated with the availability of HUFA-rich aquatic insects. Variation in aquatic insect biomass during chick development was a strong predictor of fledging success, whereas variation in terrestrial insects had little effect on fledging success. Our results highlight the potential for nutritional mismatches between insectivores and high-quality prey to affect avian reproductive performance.
In situ exploration of characteristics of macropinocytosis and size range of internalized substances in cells by 3D-structured illumination microscopy

Background Macropinocytosis can occur in various types of cells and displays multiple functions. However, real-time observation and characterization of the structures of macropinocytosis on the surface of the cell membrane is not yet possible. Materials and methods Here, we establish a real-time live cell surface imaging method using three-dimensional-structured illumination microscopy. Based on this, observation of the dynamic macropinocytosis process and morphological data of internalized structures on the surface of pancreatic cancer cells were achieved during macropinocytosis. Next, different-sized silica nanoparticles (SiO2 NPs) were used as the scale for identifying the size range of internalized substances of macropinocytosis in pancreatic cancer cells. Results and conclusion Our study not only provides a practical method and more structural data for further investigation of macropinocytosis, but also makes deeper understanding of the cell response toward nanomaterials as well as nanodrugs possible.
Towards a theory of search queries

The need to manage diverse information sources has triggered the rise of very loosely structured data models, known as dataspace models. Such information management systems must allow querying in simple ways, mostly by a form of searching. Motivated by these developments, we propose a theory of search queries in a general model of dataspaces. In this model, a dataspace is a collection of data objects, where each data object is a collection of data items. Basic search queries are expressed using filters on data items, following the basic model of Boolean search in information retrieval. We characterize semantically the class of queries that can be expressed by searching. We apply our theory to classical relational databases, where we connect search queries to the known class of fully generic queries, and to dataspaces where data items are formed by attribute-value pairs. We also extend our theory to a more powerful, associative form of searching, where one can ask for objects that are similar to objects satisfying given search conditions. Such associative search queries are shown to correspond to a very limited kind of joins. We show that the basic search language extended with associative search can exactly define the queries definable in a restricted fragment of the semijoin algebra working on an explicit relational representation of the dataspace.
Subcutaneous adipose tissue therapy reduces fat by dual X‐ray absorptiometry scan and improves tissue structure by ultrasound in women with lipoedema and Dercum disease

Lipoedema is painful nodular subcutaneous adipose tissue (SAT) on legs and arms of women sparing the trunk. People with Dercum disease (DD) have painful SAT masses. Lipoedema and DD fat resists loss by diet and exercise. Treatments other than surgery are needed. Six women with lipoedema and one with DD underwent twelve 90‐min sessions over 4 weeks. Body composition by dual X‐ray absorptiometry scan, leg volume, weight, pain, bioimpedance, tissue size by caliper and ultrasound were analysed before and after SAT therapy by paired t‐tests. There was a significant decrease from baseline to end of treatment in weight, 87.6 ± 21 to 86.1 ± 20.5 kg (P = 0.03), leg fat mass 17.8 ± 7.7 to 17.4 ± 7.6 kg (P = 0.008), total leg volume 12.9 ± 4 to 12 ± 3.5 L (P = 0.007), six of 20 calliper sites and tissue oedema. Pain scores did not change significantly. By ultrasound, six women had 22 hyperechoic masses in leg fat that resolved after treatment; five women developed seven new masses. Fascia improved by ultrasound after treatment. SAT therapy reduced amount and structure of fat in women with lipoedema and Dercum disease; studies are needed to compare SAT therapy to other therapies.
Effect of Kangaroo Mother Care on Successful Breastfeeding: A Systematic Review and Meta-Analysis of Randomised Controlled Trials.

BACKGROUND & AIMS Evaluating the effect of Kangaroo Mother Care (KMC) on breastfeeding success shows conflicting results. Regarding the importance of breastfeeding and uncertainties about its effect, this study intended to conduct a systematic review and meta-analysis of randomised controlled trials on the effect of KMC on success of breastfeeding. METHODS In this systematic review and meta-analysis study, required data were collected by searching the following keywords: breastfeeding, Breast-Feeding, "skin-to-skin", "Kangaroo Mother Care", randomized clinical trial. The following databases were searched: Google Scholar, PubMed, EMBASE, Scopus, and Cochrane Central Register of Controlled Trials. Two authors independently extracted the data. To estimate the Breast-Feeding outcome variables, CMA2 software was used. The risk of bias of studies was assessed with the criteria developed in the Cochrane Handbook. RESULTS Twenty articles were included. In the KMC and CNC groups, 1,432 and 1,410 neonates were examined. Breastfeeding success rate was higher in the KMC group within different time slots, however this difference was not statistically significant (RR=1.11(95CI, 0.93-1.34) and RR=1.13(95%CI, 0.92-1.34) based on the time slot and birth weight, respectively). The inter-groups differences in the mean scores of Infant Breast-Feeding Assessment Tool (IBFAT) were statistically significant (P<0.05). Breastfeeding was initiated very sooner in the KMC group, suggesting a statistically significant inter-groups difference -0.72(95%CI, from -0.92 to -0.53) (P<0.05). Majority of the studies had a high risk of bias. CONCLUSION Findings indicated a superiority of KMC over CNC in terms of breastfeeding success. Assessment of the complications and costs of KMC implementation is recommended.
Effects of Temperature on the Expression of Two Ovarian Differentiation-Related Genes foxl2 and cyp19a1a

Exposure to stress induces a series of responses and influences a wide range of biological processes including sex differentiation in fish. The present work investigated the molecular and physiological response to thermal stress throughout the early development stage covering the whole period of sex differentiation of bluegill, Lepomis macrochirus. Larvae were treated using three temperatures, 17, 24, and 32°C from 6 to 90 days posthatching (dph) in 30-L round tanks. There is no significant difference of the sex ratio and survival among the three temperature groups in the geographic population used in this study. Two ovarian differentiation-related genes foxl2 and cyp19a1a were detected at 7 dph suggesting that these genes have already played a role prior to sex differentiation. The expression of foxl2 reached the peak and was thermosensitive just prior to the onset of ovarian differentiation at 27 dph. Histological examination displayed that the proliferation of germ cells and ovarian differentiation were delayed at the low-temperature treatment (17°C) at 97 dph compared with higher temperatures. In conclusion, the water temperature regulates the sex differentiation of bluegill through modulation of the expression of foxl2 and cyp19a1a. A comparative study of the expression profile of sex differentiation-related genes in species will shed light on the evolution of sex-determination mechanisms and the impact of stress on sex differentiation.
Melioidosis in Sri Lanka

Until recently, Sri Lanka was not considered a country with endemic melioidosis. However, an increasing number of cases is being reported. National surveillance for melioidosis was instituted after 2008. A total of 250 culture-positive cases was recorded between 2006 and May 2017. Males predominated (71.6%). The age range was wide (2–92 years) reflecting a ubiquity of exposure. The majority (201/250, 80%) lived in rural areas. All provinces were affected. Case load increased during the two monsoonal periods (67%). There was representation of every population group including farmers (n = 44), housewives (n = 24), school children (n = 10), professionals (n = 5), businesspersons (n = 6), white-collar workers (n = 10) and blue-collar workers (n = 8). Diabetes was the predominant risk factor (n = 163, 65.2%). Clinical presentations included community-acquired sepsis and pneumonia, superficial and deep abscesses, and septic arthritis. Mortality was 20.4% (51/250). A majority (n = 212) of isolates belonged to the YLF (Yersinia-like fimbrial) clade but 38 were BTFC (B. thailandensis-like flagellum and chemotaxis). A total of 108 isolates was genotyped and 46 sequence types (STs) were identified, 40 being novel. It is clear that melioidosis is endemic in Sri Lanka with a wide geographic and demographic distribution. There is an urgent need to extend surveillance of melioidosis to under-resourced parts of the country and to populations at high risk.
Obstacle-Avoiding Open-Net Connector With Precise Shortest Distance Estimation

At the end of digital integrated circuit (IC) design flow, some nets may still be left open due to engineering change order (ECO). Resolving these opens could be quite challenging for some huge nets such as power ground nets because of a large number of obstacles and greatly distributed net components. Existing studies on multilayer obstacle-avoiding rectilinear Steiner trees may not be applicable to solve this problem because they assume the pins of an input net is a set of points, while the discrete net components in this problem can be regarded as a set of rectilinear pins. In this paper, we develop an efficient open-net connector that can deal with rectilinear pins. The proposed algorithm flow minimizes the total connection cost based on precise estimation of the shortest distance between each pair of rectilinear net components with the presence of complex obstacles. The experimental results show that the proposed flow can outperform the top-three teams of 2017 CAD contest at ICCAD and a state-of-the-art work in terms of total connection cost or runtime efficiency.