Miracle-dz/UniFAR-FTUs huggingface dataset:
Poor Generalization by Current Deep Learning Models for Predicting Binding Affinities of Kinase Inhibitors

The extreme surge of interest over the past decade surrounding the use of neural networks has inspired many groups to deploy them for predicting binding affinities of drug-like molecules to their receptors. A model that can accurately make such predictions has the potential to screen large chemical libraries and help streamline the drug discovery process. However, despite reports of models that accurately predict quantitative inhibition using protein kinase sequences and inhibitors’ SMILES strings, it is still unclear whether these models can generalize to previously unseen data. Here, we build a Convolutional Neural Network (CNN) analogous to those previously reported and evaluate the model over four datasets commonly used for inhibitor/kinase predictions. We find that the model performs comparably to those previously reported, provided that the individual data points are randomly split between the training set and the test set. However, model performance is dramatically deteriorated when all data for a given inhibitor is placed together in the same training/testing fold, implying that information leakage underlies the models’ performance. Through comparison to simple models in which the SMILES strings are tokenized, or in which test set predictions are simply copied from the closest training set data points, we demonstrate that there is essentially no generalization whatsoever in this model. In other words, the model has not learned anything about molecular interactions, and does not provide any benefit over much simpler and more transparent models. These observations strongly point to the need for richer structure-based encodings, to obtain useful prospective predictions of not-yet-synthesized candidate inhibitors.
PRESSURE PREDICTION AND UNDERBALANCED DRILLING IN THE DEEPWATER NIGER DELTA

The mechanisms that cause overpressure can be broadly classified into two categories: loading and unloading. This study looks at eight wells from the deepwater Niger Delta; the wells were evaluated with three aims in mind. The first aim was to determine shale pore pressure with the density log using the equivalent depth approach. The second aim, using depth profiles of density, velocity, resistivity, and vertical effective stress, and cross-plots, was to infer the overpressure mechanism. The third aim was to validate underbalanced drilling zones identified on the pressure-depth plot with indications observed on the drilling report, mudlog, and other post-drilling data. To discriminate clean shales intervals, a density-velocity transform based on Gardner’s (1974) relationship and GR filters were applied to the well logs. Measured pore pressures, log data, temperature data, drilling data, and mudlog data, including the end-of-well-report, were analysed for selected wells. Based on pressure-depth plots, the top of overpressure in the wells lies in the range 500 – 1200 TVDml. The equivalent depth method using the density log, when properly calibrated with measured pore pressures, can give reliable pressure prediction results, especially in the shallow section at temperatures 75°C, the equivalent depth method is unreliable. It was also noted that shale intervals may provide vertical permeability barriers and create pressure compartments in some of the wells. The predominant overpressuring mechanism in the shallow section, as evident from density and velocity reversals and, was found to be disequilibrium compaction. At greater depths (temperatures >75°C), a combination of disequilibrium compaction and unloading mechanisms appears to be responsible for overpressure in the wells. Evidence for unloading mechanisms includes formation temperatures of 80°C or greater, indications of smectite-to-illite conversion on density-sonic cross-plots, rapid increases in mud weight that sometimes approached fracture gradient, and depressed density reversals relative to velocity reversals. Finally, intervals identified as being drilled underbalanced on pressure-depth plots are consistent with drilling data, mudlog data, and information in the end-of-well reports. Specifically, increased gas (connection gas and background gas), hole washout, high torque, drilling break, and decreased D-exponent trend show strong association with zones of underbalanced drilling on pressure-depth plots.
Economic analysis of disease and control of multi-field epidemics in agriculture

Epidemics of plant diseases are estimated to cause significant economic losses in crop production. Fungicide applications are widely used to control crop diseases but incur substantial indirect costs. One essential class of indirect costs arises due to the evolution of fungicide resistance. This indirect cost must be estimated reliably to design economic policy for more sustainable use of fungicides. Such estimation is difficult because the cost depends on economic parameters and the epidemiological/evolutionary properties of crop pathogens. Even a conceptual framework for such estimation is missing. To address this problem, we combined a spatially implicit mathematical model of crop epidemics with an economic analysis at the landscape scale. We investigated how the net economic return from a landscape depends on the proportion of fungicide-treated fields. We discovered a pattern of accelerating (or decelerating) returns, contrary to expected diminishing returns. Next, we calculated the economic cost of the evolution of fungicide resistance as the difference between the optimal net return of the landscape in the absence and presence of resistance. We found that this cost depends strongly on the fungicide price, the degree of resistance, the pathogen’s basic reproduction number and the yield loss due to disease. Surprisingly, the cost declines with the fungicide price and exhibits a non-monotonic pattern as a function of the basic reproduction number. Hence, to calculate the cost, we must estimate these parameters robustly, incorporating variations in environmental conditions, crop varieties and the genetic composition of pathogen populations. Appropriate estimation of the cost of resistance evolution can inform economic policy, design dynamic fungicide pricing, and encourage more sustainable use of fungicides.
Schizosaccharomyces versatilis represents a distinct evolutionary lineage

The fission yeast species Schizosaccharomyces japonicus is currently divided into two varieties – S. japonicus var. japonicus and S. japonicus var. versatilis. Here we examine the var. versatilis isolate CBS5679. The CBS5679 genome shows 88% coding sequence identity to the reference genome of S. japonicus var. japonicus at the coding sequence level, with phylogenetic analyses suggesting that it has split from the S. japonicus lineage 25 million years ago. The CBS5679 genome contains a reciprocal translocation between chromosomes 1 and 2, together with several large inversions. The products of genes linked to the major translocation are associated with “metabolism” and “cellular assembly” ontology terms. We further show that CBS5679 does not generate viable progeny with the reference strain of S. japonicus. Although CBS5679 shares closer similarity to the “type” strain of var. versatilis as compared to S. japonicus, it is not identical to the type strain, suggesting population structure within var. versatilis. We recommend that the taxonomic status of S. japonicus var. versatilis is raised, with it being treated as a separate species, Schizosaccharomyces versatilis. Take-away The taxonomic status of Schizosaccharomyces versatilis is addressed. S. versatilis diverged from S. japonicus around 25 million years ago. S. versatilis does not produce viable progeny in crosses with S. japonicus. S. versatilis has a reciprocal translocation between chromosomes 1 and 2. The Gene Ontology terms for genes in the translocations are enriched for terms connected to “metabolism” and “cellular assembly”.
A new T Cell Receptor in Squamata Reptiles

Squamata exhibit a loss of genes for the gamma/delta T-lymphocyte receptor chains and a significant decrease in the number of V genes at the TRBV locus. Through genome analysis, I have discovered a new locus that contains V, J, C, and TM genes that have a similar structure to the classical TCR chains. This gene is viable, as demonstrated by the presence of messenger RNAs in the transcriptomes. Analyses using the AlphaFold2 program indicate that the deduced protein chain is associated with the alpha chain of the TCR. I have named this new chain “epsilon,” and it forms a new TCR alpha/epsilon. Evolutionarily, the epsilon chain arose from a duplication of the beta chain gene at the time of the divergence of amphibians and reptiles and has since been specifically maintained in Squamata.
The contribution of tropical cyclones to rainfall in northwest Australia

Northwest Australian rain gauge data is analysed to obtain new estimates of the fraction of rainfall caused by tropical cyclones (TCs), in one of the regions of the globe where this fraction is greatest. For annual rainfall, at some coastal stations more than 40% of rainfall arises from TCs. There is substantial seasonal variation in this fraction, with largest fractions occurring in the October through December period, where some stations have more than 70% of rainfall from TCs. There is a sharp gradient in this percentage away from the coastline, with inland values typically less than 30%. With the exception of a narrow coastal region in the tropics, changes in TC rainfall cannot explain recent rainfall trends in this region, with only a small number of locations exhibiting agreement between trends in total rainfall and trends in TC rainfall.
A REVISED VELOCITY-REVERSAL AND SEDIMENT-SORTING MODEL FOR A HIGH-GRADIENT, POOL-RIFFLE STREAM

Sediment-sorting processes related to varying channel-bed morphology were investigated from April to November 1993 along a 1-km pool-riffle and step-pool reach of North Saint Vrain Creek, a small mountain stream in the Rocky Mountains of northern Colorado. Measured cross-sectional areas of flow were used to suggest higher velocities in pools than in riffles at high flow. Three hundred and sixteen tracer particles, ranging in size from 16 mm to 256 mm, were placed in two separate pool-riffle-pool sequences and used to assess sediment-sorting patterns and sediment-transport competence variations. Tracer-particle depositional evidence indicated higher sediment-transport competence in pools than in riffles at high flow. Pool-riffle sediment sorting may be created by velocity reversals, and more localized sorting results from gravitational forces along the upstream sloping portion of the channel bed located at the downstream end of pools. [Key words: channel morphology, fluvial geomorphology, velocity reversal.
KCNN4 links PIEZO-dependent mechanotransduction to NLRP3 inflammasome activation

Immune cells sense the microenvironment to fine-tune their inflammatory responses. Patients with cryopyrin associated periodic syndrome (CAPS), caused by mutations in the NLRP3 gene, develop auto-inflammation triggered by non-antigenic, e.g. environmental cues. However, the underlying mechanisms are poorly understood. Here, we uncover that KCNN4, a calcium-activated potassium channel, links PIEZO-mediated mechanotransduction to NLRP3 inflammasome activation. Yoda1, a PIEZO1 agonist, lowers the threshold for NLRP3 inflammasome activation. PIEZO-mediated sensing of stiffness and shear stress increases NLRP3-dependent inflammation. Myeloid-specific deletion of PIEZO1/2 protects mice from gouty arthritis. Activation of PIEZO1 triggers calcium influx, which activates KCNN4 to evoke potassium efflux promoting NLRP3 inflammasome activation. Activation of PIEZO signaling is sufficient to activate the inflammasome in cells expressing CAPS-causing NLRP3 mutants via KCNN4. Finally, pharmacologic inhibition of KCNN4 alleviates auto-inflammation in CAPS patient cells and in CAPS-mimicking mice. Thus, PIEZO-dependent mechanical inputs augment inflammation in NLRP3-dependent diseases including CAPS. One Sentence Summary PIEZO-mediated mechanotransduction stimulates KCNN4-dependent potassium efflux to potentiate NLRP3 inflammasome activation.
Guidance, Navigation and Control

NASA seeks innovative, groundbreaking, and high-impact developments in spacecraft guidance, navigation, and control (GNC) technologies in support of future science and exploration mission requirements. This subtopic covers mission-enabling technologies that have significant size, weight and power, cost, and performance (SWaP-CP) improvements over the state-of-the-art commercial off-the-shelf (COTS) capabilities in the areas of (1) spacecraft attitude determination and control systems, (2) absolute and relative navigation systems, (3) pointing control systems, and (4) radiation-hardened GNC hardware.
Wave and Current Observations in a Tidal Inlet Using GPS Drifter Buoys

Abstract : The Wave Resolving Drifter (WRD) Buoy, developed at NPS, was refined by adding an accelerometer and utilizing horizontal Doppler velocity measurements to better resolve the wave surface motions. The WRD Buoy was validated against a Datawell Waverider-GPS buoy by comparing bulk wave statistics, wave energy spectra and wave directional spectra. The validation was performed in deep water, offshore of Monterey Bay, CA. Horizontal measurements from Doppler velocities showed improved capability, particularly in the wind-wave band. Vertical measurements were significantly improved through the addition of the accelerometer. A large array of WRD buoys was deployed in the Golden Gate channel at the entrance to San Francisco Bay and allowed to drift with the outgoing ebb current. The simultaneous deployment of many drifters provides a unique view of the details of the temporal and spatial evolution of the wave field as it propagated through regions of bathymetric and wave-current interactions. Wave heights increased as the wave field propagated over the ebb-tidal shoal and at the entrance to the channel, in the presence of a strong opposing ebb current, as expected. Inside the channel, strong dissipation of high frequency wind waves was observed in the opposing current.
Electronic Journal of Plant Breeding Research

Forty three genotypes of chilli belonging to three different species viz.,Capsicum annuum, Capsicum chinense, Capsicum frutescens were evaluated for genetic variability and divergence at College Orchard of Tamil Nadu Agricultural University, Coimbatore. The analysis of variance revealed that the germplasm lines had substantial genetic diversity. Values of close proximity between PCV and GCV indicated that the traits were mostly under genetic control and less affected by the environment. High heritability and genetic advance were observed for almost all the yield contributing traits. PCA showed that five of the 13 main components showed significant results with 77.89% of the total variance, of which the highest variability (26.50%) was exhibited by PC1. Cluster analysis showed maximum intra cluster distance in cluster 3 (515.90). Genotypes in cluster 3 and cluster 4 were genetically distant (2686.11) and can be exploited for the development of hybrid in future breeding programmes.
Coastal Circulations Driven by River Outflow

Variable-density, 1 ~and 2~-layer models are used to examine the behavior of plumes resulting from a fresher outflow of transport Mr and salinity Sr into a pre-existing oceanic layer of initial thickness HI and salinity Sj. It is found that the plumes exhibit a variety of features depending on conditions of the outflow, the situation of the anlbient ocean, and external forcing. Perhaps the most interesting feature is that the plume can flow along the upstreanl (to the left of the river mouth, looking seaward in the northern hemisphere) coast by itself, and the research discussed here is focused on this topic. To illustrate how density variations associated with river plumes drive circulations, several solutions of geostrophic adjustment to an initially-imposed, V-independent density front are investigated. In these solutions, a frontally-trapped alongfront geostrophic current with the fresher water to its right (facing in the current direction) is always generated in response to the initial pressure gradient across the density front. This density-driven geostrophic current is dynamically similar to that resulting from initial disturbances in layer thickness h (equivalently, potential vorticity q = f / h) in constant-density models, with low salinity (density) in the variable-density model being analogous to the low q in the constant-density model. Solutions to the 1 ~-layer model driven by river outflow are fundanlentally different in low-R" (Rossby number) and high-R" regimes. In the low-R" case, plumes advance along both upstream and downstream coasts. IT Mr is less than a critical value Mer (determined by /::;.S = Sj Sr and HI), plumes are coastally-trapped and all the river water;. first flows upstream, with some of it, together with some salty water, reversing direction near the plume nose to flow along the offshore front, this return flow passes the river mouth and continues to flow along the downstream (to the right of the river mouth) coast. When Mr > Mer, the plumes expand offshore indefinltely, and some river water must flow downstream directly. The evolution of the river plume for the low-Ro solutions can be understood in terms of two distinct flow patterns. One is a downstreanl coastal current ("coastal mode") directly forced by the river transport; it is dynanlically similar to the response in a linear, constantdensity, l~-layer model, and is responsible for the downstream motion. The other is an
Africa, Football and FIFA: Politics, Colonialism and Resistance

Football diffusion and colonial doctrine in Africa football, indigenous resistance and African independence FIFA, Eurocentrism and the distribution of power in world football Africa, Third World solidarity and the FIFA Presidency Havelange, African resistance and the struggle for global equity UEFA, FIFA and the scramble for Africa Africa and the campaign for the summit of world football theorizing Africa's place in FIFA's global order.
Investigating the Impact of Mobile Microlearning and Self-Regulated Learning Support on Soldiers’ Self-Efficacy and Retention within an Army Schoolhouse

The current study has shown positive evidence for the adoption of the PERvasive Learning System (PERLS) into military education and training environments. A randomized control trial was implemented to evaluate the impact of PERLS within a military classroom setting. It found that PERLS use during a course could improve soldiers’ self-efficacy for content and self-regulated learning (SRL) and potentially increase completion rates for soldiers. These findings show the possibility that correctly designed technology can support users’ self-efficacy for their ability to implement SRL. Further, this study
Technique for Estimating Magnitude and Frequency of Floods in Kentucky

Abstract: This report presents flood magnitude and frequency relations applicable to 'unregulated streams in Kentucky. The relations are based on flood data at 117 gaging stations in Kentucky and 14 in adjacent states having 10 or more years of record not significantly affected by man-made changes . Equations that relate flood magnitude and frequency to contributing drainage area in 16 geographic areas may be used to estimate magnitude of future floods with recurrence intervals of as much as 100 years on gaged and ungaged streams having drainage areas of 10 to 4,300 square miles (25 .9, to 11,100 square kilometers) . Estimating equations are also presented in graphical form for the convenience of the user . Additional graphs are presented to estimate flood magnitude for selected recurrence intervals along the Cumberland, Kentucky, and Ohio Rivers .
Park Accessibility in Atlanta

Urban green spaces, such as parks, provide urban residents with a multitude of environmental benefits and city residents should all have access to these benefits. This study examined the socioeconomic status of urban residents who live within one-mile distance to a public park in the city of Atlanta. Park accessibility was investigated with respect to distances to parks and park acreage using Euclidean distance and street-network distance. Socioeconomic status was examined using five variables: population density, median household income, percentage of population living below poverty, percentage of minority population and percentage of female population. A site suitability analysis was conducted to determine where additional park space could be most beneficial for the populations lacking access to the benefits of park space. Using Geographic Information Systems to analyze socioeconomic data from U.S. Census Bureau vis-àvis Atlanta parks, this study discovered there is no statistically significant socioeconomic disparity among residents who currently have or do not have park access in Atlanta. The findings of this study showed some weak relationships of park distance and park size with population density and minority populations. The site suitability study suggested two sites that could be potentially used for future park development. INDEX WORDS: Accessibility, Green space, GIS, Environmental justice
Topographical survey of end moraine and dead ice area at Imja Glacial Lake in 2001 and 2002

A survey was carried out at the end moraine and the dead ice area of the Imja Glacial Lake in October 2001 and in April 2002 using a digital theodolite with a laser distance meter and differential Global Positioning System (d-GPS). The survey points covered the whole dead ice area and end moraine of the Imja Glacier, and map contours were produced at 5-m intervals. This topographical map will be a significant means to analyze the time variation of the dead ice area and end moraine in future re-mapping. Changes in the lake level and the spillway on the dead ice area since 1994 were also analyzed in comparison with the measurements in 1994 by Watanabe et al. (1995).
Subglacial Hydrology for an Ice Sheet Resting on a Deformable Aquifer

Abstract Subglacial hydrology is investigated for an ice sheet where the substrate consists of a deformable aquifer resting on an aquitard. If sliding velocities are low or absent, subglacial melt-water drainage is dominated by drainage through the aquifer to water channels. Drainage along the bed is negligible. Efficient melt-water drainage requires that a system of subglacial water channels exists; otherwise, pore-water pressures will exceed the overburden pressure. In general, aquifer deformation near (away from) the terminus is most likely to occur during the winter (summer). The effect of short-term high channel pressures is, in general, not critical to aquifer deformation because the pressure pulse does not propagate far into the aquifer. (For aquifers of high permeability, short periods of high channel pressures constitute the most critical condition.) Aquifer deformation at the terminus is very likely to occur if the terminus ice slope exceeds tan ϕ, where ϕ is the Coulomb friction angle of the aquifer material. Upwelling of basal melt water near the terminus will normally cause soil dilation if the aquifer has a low permeability (e.g. till). Maximal profiles are computed corresponding to various aquifer materials using channel spacings which provide efficient drainage. (A maximal profile is the highest ice profile which the aquifer can sustain without deformation.) In general, maximal profiles lie well above observed profiles (such as h(x) = 3x 1/2 (m)) except near the terminus. However, if channel spacings are sufficiently large, pore-water pressures are increased and maximal profiles can lie well below h(x) = 3x 1/2.