Miracle-dz/UniFAR-FTUs huggingface dataset:
A photonic band-gap resonator to facilitate GHz-frequency conductivity experiments in pulsed magnetic fields

We describe instrumentation designed to perform millimeter-wave conductivity measurements in pulsed high magnetic fields at low temperatures. The main component of this system is an entirely nonmetallic microwave resonator. The resonator utilizes periodic dielectric arrays (photonic band-gap structures) to confine the radiation, such that the resonant modes have a high Q factor, and the system possesses sufficient sensitivity to measure small samples within the duration of a magnet pulse. As well as measuring the sample conductivity to probe orbital physics in metallic systems, this technique can detect the sample permittivity and permeability allowing measurement of spin physics in insulating systems. We demonstrate the system performance in pulsed magnetic fields with both electron paramagnetic resonance experiments and conductivity measurements of correlated electron systems.
A first sample of faint radio sources with virtually complete redshifts — I. Infrared images, the Hubble diagram and the alignment effect

We have obtained redshifts and infrared images for a sample of faint B2/6C radio sources, the fluxes of which are about six times fainter than those of sources in the bright 3C sample. We now have unambiguous redshifts for 90 per cent of the sources, making this the first faint radio sample with such complete redshift information. We find that the infrared Hubble diagrams (K versus z) of the 3C sample and the B2/6C sample are similar at a low redshift (z < 0.6), but by a redshift of z ~ 1 the 6C/B2 galaxies are on average ~ 0.6 mag fainter in the K-band than are 3C galaxies at the same redshift. This suggests that the bright K magnitudes of 3C galaxies at z ~ 1 are not the result of stellar evolution, but of a correlation between infrared and radio luminosity. We also find that the infrared structures of B2/6C galaxies at z ~ 1 are less clearly aligned with their radio structures than are 3C galaxies at this redshift, implying that the strength of the alignment effect depends on radio luminosity. Finally, above a redshift of 2 we find that the dispersion in the K-z relation ofthe B2/6C sample is ~2.7 times greater than that at low redshift, a result which is expected if, at these redshifts, we are beginning to penetrate into the epoch in which radio galaxies formed.
Arabidopsis pollen Prolyl-hydroxylases P4H4/6 are required for correct hydroxylation and secretion of LRX11 in pollen tubes

Major constituents of the plant cell walls are structural proteins that belong to the Hydroxyproline-rich glycoprotein family. Leucine-rich repeat extensis are contain a leucine-rich domain and a C-terminal domain with repetitive Ser-Pro(3-5) motifs plausible to be glycosylated. We have demonstrated that pollen-specific LRX8-11 from Arabidopsis thaliana are necessary to maintain the integrity of the pollen tube cell wall during polarized growth. In classical EXTs and likely in LRXs, proline residues are converted to hydroxyproline by Prolyl-4-hydroxylases, thus defining novel O-glycosylation sites. In this context, we aimed to determine whether hydroxylation and subsequent O-glycosylation of Arabidopsis pollen LRXs are necessary for their proper function and cell wall localization in pollen tubes. We hypothesized that pollen-expressed P4H4 and P4H6 catalyze the hydroxylation of the proline units present in Ser-Pro(3-5) motifs of LRX8-LRX11. Here, we show the p4h4-1 p4h6-1 double mutant exhibits a significant reduction in pollen germination rates and a slight reduction in pollen tube length. Pollen germination is also inhibited by specific P4Hs inhibitors, suggesting that prolyl hydroxylation is required for pollen tube development. Plants expressing pLRX11::LRX11-GFP in the p4h4-1 p4h6-1 background show partial relocalization of LRX11-GFP from the pollen tube tip apoplast to the cytoplasm. Finally, IP-MS- MS analysis revealed a decrease in oxidized prolines in LRX11-GFP in the p4h4-1 p4h6-1 background when compared to lrx11 plants expressing pLRX11::LRX11-GFP. Together, these results suggest that P4H4 and P4H6 are required for pollen germination and are also involved in LRX11 hydroxylation necessary for its localization at the cell wall of pollen tubes. One Sentence Summary Pollen-expressed P4H4 and P4H6 are required for pollen germination and for proper hydroxylation and secretion of LRX11 in pollen tubes.
Spatially-embedded recurrent neural networks reveal widespread links between structural and functional neuroscience findings

Brain networks exist within the confines of resource limitations. As a result, a brain network must overcome metabolic costs of growing and sustaining the network within its physical space, while simultaneously implementing its required information processing. To observe the effect of these processes, we introduce the spatially-embedded recurrent neural network (seRNN). seRNNs learn basic task-related inferences while existing within a 3D Euclidean space, where the communication of constituent neurons is constrained by a sparse connectome. We find that seRNNs, similar to primate cerebral cortices, naturally converge on solving inferences using modular small-world networks, in which functionally similar units spatially configure themselves to utilize an energetically-efficient mixed-selective code. As all these features emerge in unison, seRNNs reveal how many common structural and functional brain motifs are strongly intertwined and can be attributed to basic biological optimization processes. seRNNs can serve as model systems to bridge between structural and functional research communities to move neuroscientific understanding forward.
Fragment Linker Prediction Using the Deep Encoder-Decoder Network for PROTACs Drug Design

A drug discovery and development pipeline is a prolonged and complex process that remains challenging for both computational methods and medicinal chemists and has not been able to be resolved using computational methods. Deep learning has been utilized in various fields and achieved tremendous success in designing novel molecules in the pharmaceutical industry. Herein, we use state-of-the-art techniques to propose a deep neural network, AIMLinker, to rapidly design and generate meaningful drug-like proteolysis targeting chimeras (PROTACs) analogs. The model extracts the structural information from the input fragments and generates linkers to incorporate them. We integrate filters in the model to exclude nondruggable structures guided via protein–protein complexes while retaining molecules with potent chemical properties. The novel PROTACs subsequently pass through molecular docking, taking root-mean-square deviation (RMSD), relative Gibbs free energy (ΔΔGbinding), molecular dynamics (MD) simulation, and free energy perturbation (FEP) calculations as the measurement criteria for testing the robustness and feasibility of the model. The generated novel PROTACs molecules possess similar structural information with superior binding affinity to the binding pockets compared to the existing CRBN-dBET6-BRD4 ternary complexes. We demonstrate the effectiveness of the methodology of leveraging AIMLinker to design novel compounds for PROTACs molecules exhibiting better chemical properties compared to the dBET6 crystal pose.
The RNF220 domain nuclear factor Teyrha-Meyrha (Tey) regulates the migration and differentiation of specific visceral and somatic muscles in Drosophila

The development of the visceral musculature of the Drosophila midgut encompasses a closely coordinated sequence of migration events of cells from the trunk and caudal visceral mesoderm, respectively, that underlies the formation of the stereotypic orthogonal pattern of circular and longitudinal midgut muscles. Our current study focuses on the last step of migration and morphogenesis of the longitudinal visceral muscle precursors derived from the caudal mesoderm. We show that these multinucleated muscle precursors utilize dynamic filopodial extensions to migrate in dorsal and ventral directions over the forming midgut tube. The establishment of maximal dorsoventral distances from one another and subsequent alignment with their anteroposterior neighbors leads to the equidistant coverage of the midgut with longitudinal muscle fibers. We identify Teyrha-Meyhra (Tey), a tissue-specific nuclear factor related to the RNF220 domain protein family, as a crucial regulator of this process of muscle migration and morphogenesis that is further required for proper differentiation of the longitudinal visceral muscles. In addition, Tey is expressed in a single type of somatic muscle founder cell in each hemisegment. Tey regulates the migration of this founder cell and is required for the proper pathfinding of its developing myotube to specific myotendinous attachment sites.
Determining the toxicity and potential for environmental transport of pyridine using the brown crab Cancer pagurus (L.)

A series of mass mortalities (wash-ups) of marine life were documented along England’s north east coastline with peaks in September and October 2021, coincident with a programme of intensified maintenance dredging of the River Tees. Decapod crustaceans were the worst affected fauna, with brown crab (Cancer pagurus), European lobster (Homarus gammarus, L.), green shore crab (Carcinus maenas, L.) and velvet swimming crab (Necora puber, L.) populations severely affected. Moribund animals presented with twitching behaviours and paralysis. A potential release of the industrial pollutant pyridine was forwarded as one explanation; however, toxicology data for pyridine in decapods is lacking. In this study, we address this knowledge gap by executing a programme of immersion exposure experiments (pyridine at 2 - 100 mg L-1) using C. pagurus, measuring toxicity effects at the individual (survival) and cellular levels (cellular, mitochondrial, and lipid peroxidation reactive oxygen species (ROS) formation in the gills, hepatopancreas and claw muscle). Highest mortality rates were seen after 72 hours of exposure, returning an LC50 value of 2.75 mg L-1. Exposed crabs presented with patterns of convulsions, limb twitching, paralysis, and death. Crabs exposed to the lowest pyridine dose (2 mg L-1) were noticeably more docile than controls. Concentration was a significant factor influencing mitochondrial ROS formation at low concentrations, with tissue type, time, and their interaction all significant at 100 mg L-1. Computer simulations were used to model the transport of any pyridine released from the dredging work, demonstrating the potential for a pyridine plume to extend from Seaham to the north of the Tees to Whitby and Robin Hood’s Bay to the south. This range corresponds well with the reported wash-ups and subsequent declines in catch rates.
Simultaneous inference for proportions in arbitrary sampling designs

In these paper simultaneous confidence intervals for proportions in arbitrary sampling schemes are constructed. To accomplish this the asymptotic joint distribution of proportions is derived in arbitrary sampling designs. An application to household proportions in Germany in 1993 and Monte Carlo simulations are given. It turns out that conventional estimators fail in some sampling designs while the confidence intervals taking into account the sampling design behave well in all instances.
Renormalization of Lagrangian bias via spectral parameters

We extend the definition of Lagrangian local bias proposed by Matsubara (2008) to include curvature and higher-derivative bias operators. Evolution of initially biased tracers using perturbation theory (PT) generates multivariate bias parameters as soon as nonlinear fluctuations become important. We present a procedure that reparametrize a set of spectral parameters, the arguments of the Fourier transformed Lagrangian bias function, from which multivariate renormalized biases can be derived at any order in bias expansion and PT. We find our method simpler than previous renormalization schemes because it only relies on the definition of bias, fixed from the beginning, and in one equation relating renormalized and unrenormalized spectral parameters. We also show that our multivariate biases can be obtained within the peak background split framework, in that sense this work extends that of Schmidt, Jeong and Desjacques (2013); however, we restrict our method to Gaussian initial conditions. Non-linear evolution also leads to the appearance of products of correlators evaluated at the same point, commonly named contact terms, yielding divergent contributions to the power spectrum, in this work we present an explicit method to remove these divergences by introducing stochastic fields.
Evaluating the analytical validity of mutation calling pipeline for tumor whole exome sequencing

Detecting somatic mutations from the patients’ tumor tissues has the clinical impacts in medical decision making. Library preparation methods, sequencing platforms, read alignment tools and variant calling algorithms are the major factors to influence the data analysis results. Understanding the performance of the tool combinations of the somatic variant calling pipelines has become an important issue in the use of the whole exome sequences (WES) analysis in clinical actions. In this study, we selected four state-of-the-art sequence aligners including BWA, Bowtie2, DRAGMAP, DRAGEN aligner (DragenA) and HISAT2. For the variant callers, we chose GATK Mutect2, Sentieon TNscope, DRAGEN caller (DragenC) and DeepVariant. The benchmarking tumor whole exome sequencing data released from the FDA-led Sequencing and Quality Control Phase 2 (SEQC2) consortium was applied as the true positive variants to evaluate the overall performance. Multiple combinations of the aligners and variant callers were used to assess the variation detection capability. We measured the recall, precision and F1-score for each combination in both single nucleotide variants (SNVs) and short insertions and deletions (InDels) variant detections. We also evaluated their performances in different variant allele frequencies (VAFs) and the base pair length. The results showed that the top recall, precision and F1-score in the SNVs detection were generated by the combinations of BWA+DragenC(0.9629), Bowtie2+TNscope(0.9957) and DRAGMAP+DragenC(0.9646), respectively. In the InDels detection, BWA+DragenC(0.9546), Hisat2+TNscope(0.7519) and DragenA+DragenC(0.8081) outperformed the other combinations in the recall, precision and F1-Score, respectively. In addition, we found that the variant callers could bias the variant calling results. Finally, although some combinations yielded high accuracies of variant detection, but some variants still could not be detected by these outperformed combinations. The results of this study provided the vital information that no single combination could achieve superior results in detecting all the variants of the benchmarking dataset. In conclusion, applying both merged-based and ensemble-based variants detection approaches is encouraged to further detect variants comprehensively.
Data Mashups Privacy Preservation for Learning Analytics (Short paper)

The diversity of information sources available to educational institutions makes it necessary to mash up information in order to get the highest performance through learning analytics. Data mashup requires the implementation of data anonymisation methods in order to protect the privacy of the learners who appear in the data partitions. However, the process of anonymising this data mashup can lead to a loss of data utility. This paper presents a protocol for merging data mashups that preserves privacy by k-anonymising the data while preserving its analytical utility.
Static analysis of arithmetical congruences

In this paper, a new kind of static (or semantic) analysis is defined: congruence analysis, which is conceived to discover the properties of the following type: “the integer valued variable X is congruent to c modulo m”, where c and m are automatically determined integers. This analysis is then related to an algebraic framework and wholly characterized. Moreover, we show an example how it can be useful for automatic vectorization. Finally, we present some extensions of it, namely its combination with the analysis of bounds, and also some analyses defined when the modulus of congruences is given a priori.
Divergent roles of PD-L1 in immune regulation during ischemia–reperfusion injury

Ischemia–reperfusion (I/R) injury is a type of pathological injury that commonly arises in various diseases. Various forms of immune response are involved in the process of I/R injury. As a member of the B7 costimulatory molecule family, programmed death 1-ligand 1 (PD-L1) is an important target for immune regulation. Therefore, PD-L1 may be implicated in the regulation of I/R injury. This review briefly describes the immune response during I/R injury and how PD-L1 is involved in its regulation by focusing on findings from various I/R models. Despite the limited number of studies in this field of research, PD-L1 has shown sufficient potential as a clinical therapeutic target.
Pre-clinical evaluation of antiproteases as potential candidates for HIV-1 pre-exposure prophylaxis

Previous studies on highly HIV-1-exposed, yet persistently seronegative women from the Punwami Sex Worker cohort in Kenya, have shed light on putative protective mechanisms, suggesting that mucosal immunological factors, such as antiproteases, could be mediating resistance to HIV-1 transmission in the female reproductive tract. Nine protease inhibitors were selected for this study: serpin B4, serpin A1, serpin A3, serpin C1, cystatin A, cystatin B, serpin B13, serpin B1 and α-2-macroglobulin-like-protein 1. We assessed in a pilot study, the activity of these antiproteases with cellular assays and an ex vivo HIV-1 challenge model of human ecto-cervical tissue explants. Preliminary findings with both models, cellular and tissue explants, established an order of inhibitory potency for the mucosal proteins as candidates for pre-exposure prophylaxis when mimicking pre-coital use. Combination of all antiproteases considered in this study was more active than any of the individual mucosal proteins. Furthermore, the migration of cells out of ecto-cervical explants was blocked indicating potential prevention of viral dissemination following amplification of the founder population. These findings constitute the base for further development of these mucosal protease inhibitors for prevention strategies.
Brazilian breast cancer patient-reported outcomes: What really matters for these women

Introduction Patient-Reported Outcomes (PRO) are directly reported by the patient without interpretation of the patient's response by a clinician or anyone else and pertains to the patient's health, quality of life, or functional status associated with health care or treatment. It can provide patients’ perspectives regarding treatment benefit and harm beyond survival and are often the outcomes of most importance to patients. This study aims to describe and analyze outcomes reported by Brazilian women diagnosed with breast cancer and rank the most important attributes for these patients. Methods Observational descriptive study composed of exploratory interviews followed by online questionnaires applied to a convenience sample of women diagnosed with breast cancer. Results Twelve women were interviewed to explore the main outcomes and preferences about their treatments, such as the most common side effects and the most impacted aspects of life after diagnosis and BC treatment. Psychological, emotional, and sexual impacts were frequently described as impacted aspects. Fifty-three women, from all the five Brazilian regions, answered the online questionnaire. Following an order of importance ranking, the following outcomes were chosen, respectively: overall survival, progression-free survival; and quality of life. The treatment effects that were considered less important, among this sample, were pain and adverse events. Conclusions Thinking about expanding the therapeutic quality of users, it is essential to take into account the experiences of patients. PRO is a trend in current research to achieve this goal, in order to influence the decisions of HTA agencies about the importance of valuing outcomes that affect patients' lives.
Investigating cognitive flexibility deficit in schizophrenia using task-based whole-brain functional connectivity

Background Cognitive flexibility is a core cognitive control function supported by the brain networks of the whole-brain. Schizophrenic patients show deficits in cognitive flexibility in conditions such as task-switching. A large number of neuroimaging studies have revealed abnormalities in local brain activations associated with deficits in cognitive flexibility in schizophrenia, but the relationship between impaired cognitive flexibility and the whole-brain functional connectivity (FC) pattern is unclear. Method We investigated the task-based functional connectivity of the whole-brain in patients with schizophrenia and healthy controls during task-switching. Multivariate pattern analysis (MVPA) was utilized to investigate whether the FC pattern can be used as a feature to discriminate schizophrenia patients from healthy controls. Graph theory analysis was further used to quantify the degrees of integration and segregation in the whole-brain networks to interpret the different reconfiguration patterns of brain networks in schizophrenia patients and healthy controls. Results The results showed that the FC pattern classified schizophrenia patients and healthy controls with significant accuracy. Moreover, the altered whole-brain functional connectivity pattern was driven by a lower degree of network integration and segregation in schizophrenia, indicating that both global and local information transfers at the entire-network level were less efficient in schizophrenia patients than in healthy controls during task-switching processing. Conclusion These results investigated the group differences in FC profiles during task-switching and not only elucidated that FC patterns are changed in schizophrenic patients, suggesting that task-based FC could be used as a potential neuromarker to discriminate schizophrenia patients from healthy controls in cognitive flexibility but also provide increased insight into the brain network organization that may contribute to impaired cognitive flexibility.