Miracle-dz/UniFAR-FTUs huggingface dataset:
Development of non-sedating antischistosomal benzodiazepines

The neglected tropical disease schistosomiasis infects over 200 million people worldwide and is treated with just one broad spectrum antiparasitic drug (praziquantel). Alternative drugs are needed in the event of emerging praziquantel resistance or treatment failure. One promising lead that has shown efficacy in animal models and a human clinical trial is the benzodiazepine meclonazepam, discovered by Roche in the 1970’s. Meclonazepam was not brought to market because of dose-limiting sedative side effects. However, the human target of meclonazepam that causes sedation (GABAARs) are not orthologous to the parasite targets that cause worm death. Therefore, we were interested in whether the structure of meclonazepam could be modified to produce antiparasitic benzodiazepines that do not cause host sedation. We synthesized 18 meclonazepam derivatives with modifications at different positions on the benzodiazepine ring system and tested them for in vitro antiparasitic activity. This identified five compounds that progressed to in vivo screening in a murine model, two of which cured parasite infections with comparable potency to meclonazepam. When these two compounds were administered to mice that were run on the rotarod test, both were less sedating than meclonazepam. These findings demonstrate the proof of concept that meclonazepam analogs can be designed with an improved therapeutic index, and point to the C3 position of the benzodiazepine ring system as a logical site for further structure-activity exploration to further optimize this chemical series.
Uncovering functional lncRNAs by scRNA-seq with ELATUS

Long non-coding RNAs (lncRNAs) play fundamental roles in cellular processes and pathologies, regulating gene expression at multiple levels. Despite being highly cell type-specific, their study at single-cell (sc) level has been challenging due to their less accurate annotation and low expression compared to protein-coding genes. To identify the important, albeit widely overlooked, specific lncRNAs from scRNA-seq data, here, we develop a computational framework, ELATUS, based on the pseudoaligner Kallisto that enhances the detection of functional lncRNAs previously undetected and exhibits higher concordance with the ATAC-seq profiles in single-cell multiome data. Importantly, we then independently confirmed the expression patterns of cell type-specific lncRNAs exclusively detected with ELATUS and unveiled biologically important lncRNAs, such as AL121895.1, a previously undocumented cis-repressor lncRNA, whose role in breast cancer progression was unnoticed by traditional methodologies. Our results emphasize the necessity for an alternative scRNA-seq workflow tailored to lncRNAs that sheds light on the multifaceted roles of lncRNAs.
Analyzing the intrastate and interstate swine movement network in the United States

Disease prevention and control tactics rely on identifying and restricting animal movement to attenuate the between-premises spread of disease in livestock systems. Therefore, it is essential to uncover between-premises movement dynamics, including shipment distances and network-based control strategies. Here, we analyzed three years of between-premises pig movements, which include 197,022 unique animal shipments, 3,973 premises, and 391,625,374 pigs shipped across 20 U.S. states. We constructed unweighted, directed, temporal networks at 180-day intervals to calculate premises-to-premises movement distances, the size of connected components, network loyalty, and degree distributions, and, based on the out-going contact chains, identified network-based control actions. Our results show that the median distance between premises pig movements was 74.37 km, with median intrastate and interstate movements of 52.71 km and 328.76 km, respectively. On average, 2,842 premises were connected via 6,705 edges, resulting in a weak giant connected component that included 91% of the premises. The premises-level network exhibited loyalty, with a median of 0.65 (IQR: 0.45 – 0.77). Results highlight the effectiveness of node targeting and disease spread; we demonstrated that targeting 25% of farms with the highest degree or betweenness limited spread to 1.23% and 1.7% of premises, respectively. While there is no complete shipment data for the entire U.S., our multi-state movement analysis demonstrated the value and the needs of such data for enhancing the design and implementation of proactive-disease control tactics.
Why the brown ghost chirps at night

Since the pioneering work by Moeller, Szabo, and Bullock, weakly electric fish have served as a valuable model for investigating spatial and social cognitive abilities in a vertebrate taxon usually less accessible than mammals or other terrestrial vertebrates. These fish, through their electric organ, generate low-intensity electric fields to navigate and interact with conspecifics, even in complete darkness. The brown ghost knifefish is one of the most widely studied species due to its rich electric vocabulary, made by individually variable and sex-specific electric signals. These are mainly characterized by brief frequency modulations of the oscillating dipole moment emitted continuously by their electric organ and are known as chirps. Different types of chirps are believed to convey specific and behaviorally salient information, serving as behavioral readouts for different internal states during behavioral observations. Despite the success of this model in neuroethology over the past seven decades, the code to decipher their electric communication remains unknown. This study re-evaluates this view, aiming to offer an alternative, and possibly complementary, explanation for why these freshwater bottom dwellers emit electric chirps. By uncovering correlations among chirping, electric field geometry, and detectability in enriched environments, we present evidence for a previously unexplored role of chirps as specialized self-directed signals, enhancing conspecific electrolocation during social encounters.
The Digital Dilemma

Abstract The long-term care of collected and created data is an ethical obligation in the fields of archaeology and cultural heritage management. With the growing application of digital methodologies in these fields and the complexity of the resulting data, this task has become complicated. Digital data preservation firms have emerged since this methodological shift, but their policies—championing the democratization of academic data—may conflict with the legal obligations dictated by the countries where data originate. Scholars thus face an inevitable choice between two obligations, one ethical and one legal. While the amount of digital data grows and the options for preservation remain fundamentally misaligned with research norms and project workflows, the digital dilemma places the integrity of data at risk of loss. This article addresses this dilemma by evaluating the existing data publication, archiving, and preservation repositories and considering how, as solutions to the digital dilemma, they can be integrated into multiple workflows. I also propose new directions for archaeological associations, suggesting that they should establish a means of evaluation and approval for third-party preservation firms managing the future of academic research prior to their inevitable ubiquity.
Estimation of depth-dependent hydraulic conductivity and deformation modulus using RQD

Hydraulic conductivity is indispensable for groundwater modeling in fractured rock masses while deformation modulus is required for stability evaluation of rock masses. Unfortunately, the variations in hydraulic conductivity and deformation modulus with depth are usually ignored, which would lead to inaccurate results. The feasibility of estimating hydraulic conductivity and deformation modulus using the rock quality design (RQD) at different depths is discussed. In a granite rock mass, it is found out that the mean RQD would increase with depth, while the mean hydraulic conductivity would decrease with depth. Moreover, there is a high correlation between mean RQD and mean hydraulic conductivity. Therefore, it is practical to estimate depth-dependent hydraulic conductivity using RQD data. Furthermore, based on empirical equations, the deformation modulus is successfully estimated using the variations in mean RQD with depth.
α-Glucosidase and α-Amylase Inhibitory Compounds from three African Medicinal Plants: An Enzyme Inhibition Kinetics Approach

The quest to find new lead compounds with anti-diabetic effects via the inhibition of α-glucosidase and α-amylase had led us to conduct bioassay guided isolation of three African medicinal plants which resulted in the identification of bicyclo[2.2. 0]hexane-2,3,5-triol (1), 3β-O-acetyl betulinic acid (2) and 2,7-dihydroxy-4H-1-benzopyran-4-one (3), as the bioactive compounds. The compounds demonstrated a significant (P < 0.05) inhibitory effect on α-glucosidase and α-amylase activities than acarbose. Steady state kinetic analysis revealed that compounds 1 and 2 inhibited both α-amylase and α-glucosidase in non-competitive patterns whilst compound 3 was an uncompetitive inhibitor of α-glucosidase and a non-competitive inhibitor of α-amylase. In conclusion, the study has identified three new active α-glucosidase and α-amylase inhibitory compounds that could have the potential to retard postprandial hyperglycemia.
Research on the concentration of tourist arrivals in Romania.

The paper aimed to analyze the concentration of tourist arrivals in Romania based on National Institute of Statistics Data for the period 2008-2013. In Romania the tourists arrivals increased reflecting a higher demand for touristic attractions of the country. In 2013, the number of tourist arrivals accounted for 7,943,153, being by 11.47 % higher than in 2008, when it was 7,125,307 arrivals. The highest number of tourist arrivals is in the Centre, Bucuresti-Ilfov and South East regions, totalizing 56.19 % of the total number of tourist arrivals, and the lowest number of tourists was recorded in South West Oltenia. The regions where the number of tourists increased were Centre, BucurestiIlfov, South West, North East and West, and the regions where the number of tourist arrivals declined were the South East, South Muntenia and North West. The Herfindhal-Hirschman Index has small values, closer to zero, reflecting a relative uniformity among regions. It varied between 0.1387 in 2008 and 1.490 in 2013. The Gini-Struck Coefficient ranged between 0.1252 in the year 2008 and 0.1658 in the year 2013, reflecting again a relative uniform distribution of tourists arrivals by development region, in all the years, except 2012, when its value accounted for 0.51, reflecting a moderate concentration among regions. The low degree of concentration is justified by the large variety of attractions Romania could offer in all the regions. It is about cultural heritage, historical place, landscapes, gastronomy, accommodation units at various prices.
Actitudes docentes hacia la educación inclusiva en Cuenca

La definición de educación inclusiva durante años ha sufrido importantes cambios, los cuales finalmente llevaron a visualizar que la educación es un derecho para todos. El presente estudio analizó actitudes de los profesores hacia la educación inclusiva en escuelas primarias públicas y privadas de la ciudad de Cuenca. La metodología fue de tipo transversal cuantitativa, utilizando una adaptación del cuestionario de Tárraga et al. (2013). Esta versión modificada fue aplicada para estudiar una población de 650 docentes, seleccionados en base al método probabilístico estratificado. Después de un análisis preliminar de la confiabilidad y dimensionalidad del cuestionario, la escala se redujo de veinte y cinco a quince ítems, y de cuatro a tres componentes. Los resultados revelaron que los profesores en general tienen una actitud indiferente tendiendo a favorable hacia la educación inclusiva. Se encontró que actitudes más positivas están asociadas a docentes jóvenes con pocos años de servicio. No se encontró una relación significativa entre actitud y sexo, pero se encontró una asociación con la capacitación, su nivel de educación y experiencia previa con niños de educación inclusiva y el apoyo institucional (público o privado). Sin embargo, los grupos de comparación fueron desiguales en tamaño, posiblemente los resultados no podrían ser generalizados.
12 Mamluk and Mongol Peripheral Politics: Asserting Sovereignty in the Middle East’s ‘Kurdish Zone’ (1260–1330)

Scholars of the medieval Islamic world, as well as those who focus exclusively on the history of the Kurds, have paid scant attention to the impact of border geo-political transformation in the fourteenth century on both the ethnic and ethno-territorial identity of the Kurdish people.1 It is the contention of this article that this omission is a grave error, and that the emergence of military and political rivalries between the Mamluks of Egypt and the Ilkhanids of Iran over the Middle East’s ‘Kurdish zone’ constitute a key historical moment in the formation of the Kurdish identity.2 In historical terms, conceptions of Kurdish territoriality most certainly pre-date the fourteenth century; nevertheless, faced with the overawing power of the Mongol war machine and in order to offset their military inferiority outside Egypt and Syria, the Mamluks adopted a relatively novel set of strategies and policies towards the Kurdish populated highlands of western Asia. These policies in turn had a significant impact on Kurdish ‘ethnicity,’ not only raising its political significance but also territorializing it.3
Eﬀect of weed management on the growth, yield, and quality of summer maize

A �ield experiment was conducted during the summer, 2019 at the N.M. College of Agriculture Farm, Navsari Agricultural University, Navsari, Gujaratto �inds eﬀective weed management practices in summer maize cultivation.The results revealed signi�icantly higher grain and straw yield (6473 and 8041 kg/ha, respectively) with treatment T (Weed free), which was 2 statistically at par with treatment T (Pendimethalin (EC) @ 1.5 kg/ha as PE + 1 H.W. at 30 DAS. 6 Among the herbicidal treatments, signi�icantly higher growth and yield parameters viz.plant height, number of leaves per plant, number of grains per cob, grain weight per cob, 100 grain weight and protein content (%) were recorded in T (Pendimethalin (EC) @ 1.5 kg/ ha as PE + 1 6 H.W. at 30 DAS) which was followed by treatment T (Pendimethalin EC @ 1.0 kg/ ha as PE +1 5 H.W. at 30 DAS). The lowest grain yield, straw yield and protein content were observed under the treatment T (Unweeded control). 1
THE PERFORMANCE IMPLICATIONS OF ALLIANCE AND INTEGRATION GOVERNANCE MODES IN PLATFORM ECOSYSTEMS

We investigate the performance consequences of alliance versus vertical integration choices of platform participants. We apply insights from transaction cost economics to platform ecosystems by highlighting the importance of ecosystem positioning for the performance outcomes of this ally versus integrate choice. Analyzing 16,656 video game releases by 1,775 developers, 476 publishers, and 4 platform owners across 21 video game platforms between 1989 and 2017, we find that alliances outperform vertical integration, alliances with an owner outperforms alliances between two (non-owner) complementor firms. Despite positive product performance advantages of alliances in platform ecosystems, we found that these benefits diminish with platform diffusion. Our results confirm our conjecture that the coordination benefits of platform ecosystems are more salient for the participants during the early stages of the platform. As platforms matures, the significant performance differences among difference governance forms diminish.
Variation in the realization of Ukrainian back fricatives as onset lenition and non-markedness reducing coda neutralization: a 3D/4D ultrasound study

A 3D/4D ultrasound analysis of Ukrainian back fricatives provides evidence for onset lenition (debuccalization) and non-markedness reducing place neutralization in the coda (neutralization to the uvular place of articulation). These findings impinge on the role of markedness in predicting synchronic alternations and the direction of sound change. Analyses that rely on markedness as a motivating factor for synchronic patterns of alternations allow for the possibility of coda lenition, but not of onset lenition. However, the analyzed data instantiate debuccalization, a type of lenition, in the onset. Moreover, the observed retraction of place in the coda, resulting in uvular fricatives, is similarly difficult to derive from markedness principles. These findings are not compatible with the view that synchronic alternations must be driven by markedness reduction and suggest that (i) models of synchronic phonology must be designed in such a way as to accommodate segmental alternations that are arbitrary from the point of view of markedness principles, and (ii) reduction of representational complexity cannot be reliably viewed as the driver of neutralization processes.
Systematic detection of brain protein-coding genes under positive selection during primate evolution and their roles in cognition

The human brain differs from that of other primates, but the genetic basis of these differences remains unclear. We investigated the evolutionary pressures acting on almost all human protein-coding genes (N = 11,667; 1:1 orthologs in primates) based on their divergence from those of early hominins, such as Neanderthals, and non-human primates. We confirm that genes encoding brain-related proteins are among the most strongly conserved protein-coding genes in the human genome. Combining our evolutionary pressure metrics for the protein-coding genome with recent data sets, we found that this conservation applied to genes functionally associated with the synapse and expressed in brain structures such as the prefrontal cortex and the cerebellum. Conversely, several genes presenting signatures commonly associated with positive selection appear as causing brain diseases or conditions, such as micro/macrocephaly, Joubert syndrome, dyslexia, and autism. Among those, a number of DNA damage response genes associated with microcephaly in humans such as BRCA1, NHEJ1, TOP3A, and RNF168 show strong signs of positive selection and might have played a role in human brain size expansion during primate evolution. We also showed that cerebellum granule neurons express a set of genes also presenting signatures of positive selection and that may have contributed to the emergence of fine motor skills and social cognition in humans. This resource is available online and can be used to estimate evolutionary constraints acting on a set of genes and to explore their relative contributions to human traits.
Slip‐behavior transitions of a heterogeneous linear fault

Geological faults have frictional heterogeneity. Here we investigate the slip behavior of such heterogeneous faults in the simplest situation, simulating antiplane shear slip along an infinite linear fault in a 2‐D elastic model space, subjected to constant loading by external stresses characterized by stiffness and plate‐motion velocity. The fault is discretized into many subfaults, each of which has either a velocity‐weakening (VW) or velocity‐strengthening (VS) friction law. We vary the proportion of the fault that is VW, revealing several different regimes of slip behavior. The first regime boundary, where stick‐slip behavior is initiated, is located at the proportion of VW zones such that each VW zone reaches its nucleation size. The other boundary is located where the spatially averaged a − b value of the rate and state friction law is close to zero. Below this density, the VW zone slips seismically, whereas the VS zone shows afterslip. In contrast, above this density, the entire fault slips simultaneously at the seismic slip velocity. We observe transitional behavior at the second boundary, where relatively slower deformation dominates. We also explore the slip behavior of faults using Cantor‐set distributions of frictional parameters. We propose that frictional heterogeneity on the fault may explain not only the diversity of seismic phenomena but also the observed scaling of frictional parameters, such as slip‐weakening distance or the fracture energy of ordinary earthquakes.
CAMBRIDGE WORKING PAPERS IN ECONOMICS The Intergenerational Elasticity of Earnings: Exploring the Mechanisms

Using data covering a single cohort's first 55 years of life, we show that most of the intergenerational elasticity of earnings (IGE) is explained by differences in: years of schooling, cognitive skills, investments of parental time and school quality, and family circumstances during childhood. To decompose the fraction of the IGE explained by each of these channels, we implement a multi-level mediation analysis combined with a latent factor framework that accounts for measurement error. Multilevel mediation analysis allows us to assess not only the direct effect of each channel on the IGE, but also its indirect effects working through the other channels, thus providing an in-depth understanding of the link between parents' and children's earnings. Of these channels, we show that the main driver of the IGE is increased levels of parental investments received by children of high income parents early in their lives, which encourages greater cognitive development and lifetime earnings. Reference Details CWPE 2171 Published 20 October 2021
Using FCOS and an Encoder-Decoder Model to Detect and Recognize Visual Mathematical Equations

Many datasourceson the Internet contain math information within them, and math is used throughout daily life while being important for avenues of study and industry. Understanding math enables better problem solving, pattern comprehension, quantifying relationships, and making predictions of the future. Unfortunately, less people have proﬁciency in math in recent times. To make the situation worse, it is diﬃcult to locate sources of relevant math information, particularly when the searcher has little familiarity with the subject area. Having Math Information Retrieval (IR) systems would help facilitate searches for math information and assist learners with understanding math concepts. Sadly, extracting mathematical notation in graphical representations into a standardized text-based format is a non-trivial task, since it is required to detect unique symbols and spatial arrangements of mathematical characters, as well as formula positioning in documents. Failure to correctly detecting and recognizing visual math formulas and their notation produce errors that alter the entire meaning of the resulting formulas, or simply do not have the speed needed for a real-time Math IR system. To address these problems, we have developed a combined FCOS and Image2Latex framework to detect and extract math formulas from images and translate them accurately into LaTeX in a reasonable time frame.
Phase-ﬁeld modeling of contact line dynamics

The wetting dynamics on solid surfaces has been a long-standing problem, since the traditional sharp-interface Navier-Stokes formulation encounters a non-integrable stress singularity at the contact line. In recent years, the phase-ﬁ eld model, which regularizes the contact-line singularity by Cahn-Hilliard diffusion